37 results on '"Taye H Hamza"'
Search Results
2. Genome-wide gene-environment study identifies glutamate receptor gene GRIN2A as a Parkinson's disease modifier gene via interaction with coffee.
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Taye H Hamza, Honglei Chen, Erin M Hill-Burns, Shannon L Rhodes, Jennifer Montimurro, Denise M Kay, Albert Tenesa, Victoria I Kusel, Patricia Sheehan, Muthukrishnan Eaaswarkhanth, Dora Yearout, Ali Samii, John W Roberts, Pinky Agarwal, Yvette Bordelon, Yikyung Park, Liyong Wang, Jianjun Gao, Jeffery M Vance, Kenneth S Kendler, Silviu-Alin Bacanu, William K Scott, Beate Ritz, John Nutt, Stewart A Factor, Cyrus P Zabetian, and Haydeh Payami
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Genetics ,QH426-470 - Abstract
Our aim was to identify genes that influence the inverse association of coffee with the risk of developing Parkinson's disease (PD). We used genome-wide genotype data and lifetime caffeinated-coffee-consumption data on 1,458 persons with PD and 931 without PD from the NeuroGenetics Research Consortium (NGRC), and we performed a genome-wide association and interaction study (GWAIS), testing each SNP's main-effect plus its interaction with coffee, adjusting for sex, age, and two principal components. We then stratified subjects as heavy or light coffee-drinkers and performed genome-wide association study (GWAS) in each group. We replicated the most significant SNP. Finally, we imputed the NGRC dataset, increasing genomic coverage to examine the region of interest in detail. The primary analyses (GWAIS, GWAS, Replication) were performed using genotyped data. In GWAIS, the most significant signal came from rs4998386 and the neighboring SNPs in GRIN2A. GRIN2A encodes an NMDA-glutamate-receptor subunit and regulates excitatory neurotransmission in the brain. Achieving P(2df) = 10(-6), GRIN2A surpassed all known PD susceptibility genes in significance in the GWAIS. In stratified GWAS, the GRIN2A signal was present in heavy coffee-drinkers (OR = 0.43; P = 6×10(-7)) but not in light coffee-drinkers. The a priori Replication hypothesis that "Among heavy coffee-drinkers, rs4998386_T carriers have lower PD risk than rs4998386_CC carriers" was confirmed: OR(Replication) = 0.59, P(Replication) = 10(-3); OR(Pooled) = 0.51, P(Pooled) = 7×10(-8). Compared to light coffee-drinkers with rs4998386_CC genotype, heavy coffee-drinkers with rs4998386_CC genotype had 18% lower risk (P = 3×10(-3)), whereas heavy coffee-drinkers with rs4998386_TC genotype had 59% lower risk (P = 6×10(-13)). Imputation revealed a block of SNPs that achieved P(2df)
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- 2011
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3. Progressive Left Ventricular Remodeling for Predicting Mortality in Children With Dilated Cardiomyopathy: The Pediatric Cardiomyopathy Registry
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Paul F. Kantor, Ling Shi, Steven D. Colan, E. John Orav, James D. Wilkinson, Taye H. Hamza, Steven A. Webber, Charles E. Canter, Jeffrey A. Towbin, Melanie D. Everitt, Elfriede Pahl, Stephanie M. Ware, Paolo G. Rusconi, Jacqueline M. Lamour, John L. Jefferies, Linda J. Addonizio, and Steven E. Lipshultz
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cardiac transplantation ,dilated cardiomyopathy ,heart failure ,pediatrics ,remodeling ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background Pediatric dilated cardiomyopathy often leads to death or cardiac transplantation. We sought to determine whether changes in left ventricular (LV) end‐diastolic dimension (LVEDD), LV end‐diastolic posterior wall thickness, and LV fractional shortening (LVFS) over time may help predict adverse outcomes. Methods and Results We studied children up to 18 years old with dilated cardiomyopathy, enrolled between 1990 and 2009 in the Pediatric Cardiomyopathy Registry. Changes in LVFS, LVEDD, LV end‐diastolic posterior wall thickness, and the LV end‐diastolic posterior wall thickness:LVEDD ratio between baseline and follow‐up echocardiograms acquired ≈1 year after diagnosis were determined for children who, at the 1‐year follow‐up had died, received a heart transplant, or were alive and transplant‐free. Within 1 year after diagnosis, 40 (5.0%) of the 794 eligible children had died, 117 (14.7%) had undergone cardiac transplantation, and 585 (73.7%) had survived without transplantation. At diagnosis, survivors had higher median LVFS and lower median LVEDD Z scores. Median LVFS and LVEDD Z scores improved among survivors (Z score changes of +2.6 and −1.1, respectively) but remained stable or worsened in the other 2 groups. The LV end‐diastolic posterior wall thickness:LVEDD ratio increased in survivors only, suggesting beneficial reverse LV remodeling. The risk for death or cardiac transplantation up to 7 years later was lower when LVFS was improved at 1 year (hazard ratio [HR], 0.83; P=0.004) but was higher in those with progressive LV dilation (HR, 1.45; P
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- 2024
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4. Surgery or Endovascular Therapy for Chronic Limb-Threatening Ischemia
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Alik Farber, Matthew T. Menard, Michael S. Conte, John A. Kaufman, Richard J. Powell, Niteesh K. Choudhry, Taye H. Hamza, Susan F. Assmann, Mark A. Creager, Mark J. Cziraky, Michael D. Dake, Michael R. Jaff, Diane Reid, Flora S. Siami, George Sopko, Christopher J. White, Max van Over, Michael B. Strong, Maria F. Villarreal, Michelle McKean, Ezana Azene, Amir Azarbal, Andrew Barleben, David K. Chew, Leonardo C. Clavijo, Yvan Douville, Laura Findeiss, Nitin Garg, Warren Gasper, Kristina A. Giles, Philip P. Goodney, Beau M. Hawkins, Christine R. Herman, Jeffrey A. Kalish, Matthew C. Koopmann, Igor A. Laskowski, Carlos Mena-Hurtado, Raghu Motaganahalli, Vincent L. Rowe, Andres Schanzer, Peter A. Schneider, Jeffrey J. Siracuse, Maarit Venermo, and Kenneth Rosenfield
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General Medicine - Abstract
Patients with chronic limb-threatening ischemia (CLTI) require revascularization to improve limb perfusion and thereby limit the risk of amputation. It is uncertain whether an initial strategy of endovascular therapy or surgical revascularization for CLTI is superior for improving limb outcomes.In this international, randomized trial, we enrolled 1830 patients with CLTI and infrainguinal peripheral artery disease in two parallel-cohort trials. Patients who had a single segment of great saphenous vein that could be used for surgery were assigned to cohort 1. Patients who needed an alternative bypass conduit were assigned to cohort 2. The primary outcome was a composite of a major adverse limb event - which was defined as amputation above the ankle or a major limb reintervention (a new bypass graft or graft revision, thrombectomy, or thrombolysis) - or death from any cause.In cohort 1, after a median follow-up of 2.7 years, a primary-outcome event occurred in 302 of 709 patients (42.6%) in the surgical group and in 408 of 711 patients (57.4%) in the endovascular group (hazard ratio, 0.68; 95% confidence interval [CI], 0.59 to 0.79; P0.001). In cohort 2, a primary-outcome event occurred in 83 of 194 patients (42.8%) in the surgical group and in 95 of 199 patients (47.7%) in the endovascular group (hazard ratio, 0.79; 95% CI, 0.58 to 1.06; P = 0.12) after a median follow-up of 1.6 years. The incidence of adverse events was similar in the two groups in the two cohorts.Among patients with CLTI who had an adequate great saphenous vein for surgical revascularization (cohort 1), the incidence of a major adverse limb event or death was significantly lower in the surgical group than in the endovascular group. Among the patients who lacked an adequate saphenous vein conduit (cohort 2), the outcomes in the two groups were similar. (Funded by the National Heart, Lung, and Blood Institute; BEST-CLI ClinicalTrials.gov number, NCT02060630.).
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- 2022
5. Baseline Modern Medical Management in the BEST-CLI Trial
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Matthew T. Menard, Michael R. Jaff, Alik Farber, Kenneth Rosenfield, Michael S. Conte, Christopher J. White, Joshua A. Beckman, Niteesh K. Choudhry, Leonardo C. Clavijo, Thomas S. Huber, Katherine R. Tuttle, Taye H. Hamza, Andres Schanzer, Igor A. Laskowski, Mark J. Cziraky, Alain Drooz, Max van Over, Michael B. Strong, and Ido Weinberg
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Surgery ,Cardiology and Cardiovascular Medicine - Published
- 2023
6. Relationship between WIfI (wound, ischemia, foot infection) stage and quality of life at revascularization in the BEST-CLI (best endovascular versus best surgical therapy in patients with chronic limb threatening ischemia) trial
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Jeffrey J. Siracuse, Vincent L. Rowe, Matthew T. Menard, Kenneth Rosenfield, Michael S. Conte, Richard Powell, Leonardo C. Clavijo, Kristina A. Giles, Taye H. Hamza, Max Van Over, Mark Cziraky, Christopher J. White, Michael B. Strong, and Alik Farber
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Surgery ,Cardiology and Cardiovascular Medicine - Published
- 2023
7. Relationship between WIfI Stage and Quality of Life at the time of Revascularization in the BEST-CLI Trial
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Jeffrey J, Siracuse, Vincent L, Rowe, Matthew T, Menard, Kenneth, Rosenfield, Michael, Conte, Richard, Powell, Leonardo C, Clavijo, Kristina A, Giles, Taye H, Hamza, Max, Van Over, Mark, Cziraky, Christopher J, White, Michael B, Strong, and Alik, Farber
- Abstract
WIfI stage measures the extent of wounds, ischemia, and foot infection in patients with chronic limb threatening ischemia (CLTI) and has been associated with risk of major amputation. Patients with CLTI have impaired health-related quality of life (HRQoL), which may be multifactorial in nature. We hypothesize that severity of limb threat (WIfI) is associated with poor QoL among patients with CLTI presenting for revascularization.The dataset of the Best Endovascular versus Best Surgical Therapy in Patients with CLTI (BEST-CLI) trial, a prospective randomized trial comparing open and endovascular revascularization strategies, was queried for HRQoL assessment at time of patient enrollment. HRQOL assessments included (1) Vascular Quality of Life (VascuQoL), (2) SF-12, containing (a) utility index score (SF-6D-R2) - incorporating physical, emotional, and mental wellbeing, (b) mental (MCS) and (c) physical (PCS) components, and (3) EQ-5D. Multivariable regression analysis was used to identify independent associations with baseline HRQoL assessments.There were 1568 patients with complete WIfI data analyzed, of which 71.5% were male. WIfI distribution was 35.5% stage 4, 29.6% stage 3, 28.6% stage 2, and 6.3% stage 1 patients. Patients presenting with WIfI stage 4, compared to stages 1-3, were more often male (74.9% vs. 69.6%), current smokers (25.4% vs. 17.6%), had end stage renal disease (13.3% vs. 8.5%), diabetes (83.6% vs. 60.2%), were not independently ambulatory (56.8% vs. 38.5%), and had higher median morbidity score (4 vs. 3) (P.05 for all). On multivariable analysis, WIfI stage 4, compared to stages 1-3, was associated with lower SF-12 MCS (-2.43, 95% CI -3.73, -1.13, P.001) and SF6D-R2 Utility index scores (-.02, 95% CI -.03-.001, P=.04). WIfI stage was not independently associated with baseline VascuQoL, SF-12 PCS, or EQ-5D assessment.WIfI stage is independently associated with poorer quality of life due to mental rather than physical health in patients with CLTI. Clinicians should be aware of the burden of mental stress borne by those with greatest limb impairment.
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- 2022
8. Clinical practice patterns and ascertainment bias for cardiovascular events in a randomized trial: A survey of investigators in the BEST-CLI trial
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Kenneth Rosenfield, Maria F. Villarreal, Matthew T. Menard, Mazen Albaghdadi, Sandra Siami, Michael Strong, Mohammed M. Chowdhury, Susan F. Assmann, Taye H. Hamza, Alik Farber, and Michael N. Young
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Chronic Limb-Threatening Ischemia ,medicine.medical_specialty ,Time Factors ,Blinding ,Critical Illness ,medicine.medical_treatment ,030204 cardiovascular system & hematology ,Revascularization ,Amputation, Surgical ,law.invention ,Peripheral Arterial Disease ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,Risk Factors ,law ,medicine ,Humans ,030212 general & internal medicine ,Practice Patterns, Physicians' ,Cardiac risk ,Sampling bias ,business.industry ,Incidence (epidemiology) ,Endovascular Procedures ,Critical limb ischemia ,Limb Salvage ,Clinical Practice ,Cross-Sectional Studies ,Treatment Outcome ,Emergency medicine ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business - Abstract
Ascertainment bias is a well-recognized source of bias in research, but few studies have systematically analyzed sources of ascertainment bias in randomized trials in which blinding is not possible and endpoint assessment is not protocolized. In the current study, we sought to evaluate differences in the clinical practice patterns of trial investigators with respect to bias in the ascertainment of pre-revascularization patient risk and the incidence of secondary endpoints post-revascularization. We conducted a cross-sectional survey of active investigators ( n = 936) from the Best Endovascular Versus Best Surgical Therapy for Patients with Critical Limb Ischemia (BEST-CLI) trial. The total survey response rate was 19.6% (183/936). Vascular surgeons were more likely than nonsurgical interventionalists to order tests for cardiac complications after both surgical bypass ( p < 0.001) and endovascular revascularization ( p = 0.038). Post-procedure, investigators were more likely to order additional testing for cardiac complications in open surgery versus endovascular cases (7% vs 16% never, 41% vs 65% rarely, 43% vs 17% sometimes, 9% vs 2% always, respectively; p < 0.0001). Significant variation in practice patterns exist in the pre- and post-procedure assessment of cardiac risk and events for patients with CLI undergoing revascularization. Variation in the ascertainment of risk and outcomes according to the type of revascularization procedure and physician specialty should be considered when interpreting the results of clinical studies, such as the BEST-CLI trial. ClinicalTrials.gov Identifier: NCT02060630
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- 2021
9. Participation in a Chronic Limb Threatening Ischemia Randomized Trial Is Inversely Correlated With Regional Amputation Rate in Limb Threatening Ischemia Patients
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Jeffrey J, Siracuse, Philip P, Goodney, Matthew T, Menard, Kenneth, Rosenfield, Maxwell, Van Over, Taye H, Hamza, Mark, Eid, Maria F, Villarreal, Michael B, Strong, and Alik, Farber
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Male ,Research Subjects ,Endovascular Procedures ,Limb Salvage ,Amputation, Surgical ,United States ,Peripheral Arterial Disease ,Treatment Outcome ,Lower Extremity ,Ischemia ,Humans ,Female ,Aged ,Retrospective Studies - Abstract
The National Health Service demonstrated that regions of the United Kingdom with the highest number of patients enrolled in research studies had the lowest risk-adjusted mortality when patients were admitted to the hospital. Our goal was to investigate if this correlation was evident for patients with chronic limb threatening ischemia (CLI) treated in the United States (US). Accordingly, we examined correlations among sites participating in the Best Endovascular versus best Surgical Therapy in patients with Critical (BEST-CLI) trial, a multicenter, National Institute of Health-sponsored, international randomized controlled trial (RCT) comparing revascularization strategies in patients with CLI, and regional rates of major amputation from CLI.We measured regional participation in the BEST-CLI trial by evaluating trial participation and enrollment rosters. To determine regional rates of lower limb amputation, we queried the Medicare database (2007-2016) for patients with concurrent peripheral arterial disease (PAD) and diabetes, then assessed how many had lower extremity amputations. Correlation of regional amputation rates with distribution of BEST-CLI sites in four US geographical regions was calculated using Pearson's correlation coefficients. Simple regression equations were used to calculate the significance of these correlation coefficients.Of 9,231,909 CLI patients, 342,406 underwent amputation in the Medicare dataset. Amputation rates per 1000 CLI patients differed by region (South 40.42, Midwest 40.12, West 34.81, Northeast 31.14). There were 116 US vascular centers, selected by volume and expertise that participated in BEST-CLI with the following distribution: South (n = 30, 26%), Midwest (n = 26, 22%), West (n = 29, 25%), and Northeast (n = 31, 27%). There was a negative correlation between the number of amputations per 1000 for Medicare CLI patients with diabetes and PAD and the number of BEST-CLI sites in the region which trended toward significance (Pearson R= -0.61, P = 0.39).Amputation rate among Medicare CLI patients is inversely correlated with US BEST-CLI site distribution. Higher participation in clinical research, especially within large RCTs, may be a marker of optimal PAD management.
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- 2021
10. Participation in a Chronic Limb Threatening Ischemia (CLI) Randomized Trial Is Inversely Correlated With Regional Amputation Rate in CLI Patients
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Maxwell Van Over, Taye H Hamza, Alik Farber, Michael Strong, Jeffrey J. Siracuse, Philip P. Goodney, Kenneth Rosenfield, Mark A. Eid, Matthew T. Menard, and Maria F. Villarreal
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medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Ischemia ,Retrospective cohort study ,medicine.disease ,Revascularization ,law.invention ,body regions ,Clinical research ,Randomized controlled trial ,Amputation ,law ,Internal medicine ,Diabetes mellitus ,medicine ,Research studies ,Surgery ,business - Abstract
Objective The National Health Service demonstrated that regions of the United Kingdom with the highest number of patients enrolled in research studies had the lowest risk-adjusted mortality when patients were admitted to the hospital. Our goal was to investigate if this correlation was evident for patients with chronic limb threatening ischemia (CLI) treated in the United States (US). Accordingly, we examined correlations among sites participating in the Best Endovascular versus best Surgical Therapy in patients with Critical (BEST-CLI) trial, a multicenter, National Institute of Health-sponsored, international randomized controlled trial (RCT) comparing revascularization strategies in patients with CLI, and regional rates of major amputation from CLI. Methods We measured regional participation in the BEST-CLI trial by evaluating trial participation and enrollment rosters. To determine regional rates of lower limb amputation, we queried the Medicare database (2007-2016) for patients with concurrent peripheral arterial disease (PAD) and diabetes, then assessed how many had lower extremity amputations. Correlation of regional amputation rates with distribution of BEST-CLI sites in four US geographical regions was calculated using Pearson's correlation coefficients. Simple regression equations were used to calculate the significance of these correlation coefficients. Results Of 9,231,909 CLI patients, 342,406 underwent amputation in the Medicare dataset. Amputation rates per 1000 CLI patients differed by region (South 40.42, Midwest 40.12, West 34.81, Northeast 31.14). There were 116 US vascular centers, selected by volume and expertise that participated in BEST-CLI with the following distribution: South (n = 30, 26%), Midwest (n = 26, 22%), West (n = 29, 25%), and Northeast (n = 31, 27%). There was a negative correlation between the number of amputations per 1000 for Medicare CLI patients with diabetes and PAD and the number of BEST-CLI sites in the region which trended toward significance (Pearson R= -0.61, P = 0.39). Conclusions Amputation rate among Medicare CLI patients is inversely correlated with US BEST-CLI site distribution. Higher participation in clinical research, especially within large RCTs, may be a marker of optimal PAD management.
- Published
- 2021
11. Long-Term Survival Following Multivessel Revascularization in Patients With Diabetes
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Michael E. Farkouh, Michael Domanski, George D. Dangas, Lucas C. Godoy, Michael J. Mack, Flora S. Siami, Taye H. Hamza, Binita Shah, Giulio G. Stefanini, Mandeep S. Sidhu, Jean-François Tanguay, Krishnan Ramanathan, Samin K. Sharma, John French, Whady Hueb, David J. Cohen, Valentin Fuster, Tanim N. Zazif, Hoang Thai, Jeffrey R Burton, Erick Schampaert, Jorge Escobedo, Jean-Luc Dubois-Rande, Carlos Macaya, Didier Carrie, Gert Richardt, Ariel Roguin, Chaim Lotan, Ran Kornowski, Patrizia Presbitero, J. Eduardo Sousa, Jorge G. Velásquez, Alfredo Rodriguez, Gerry Devlin, John K. French, and Upendra Kaul
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medicine.medical_specialty ,Proportional hazards model ,business.industry ,medicine.medical_treatment ,Mortality rate ,Hazard ratio ,Percutaneous coronary intervention ,030204 cardiovascular system & hematology ,Revascularization ,medicine.disease ,Coronary artery disease ,03 medical and health sciences ,surgical procedures, operative ,0302 clinical medicine ,Internal medicine ,Cohort ,Conventional PCI ,medicine ,Cardiology ,cardiovascular diseases ,030212 general & internal medicine ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background The FREEDOM (Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease) trial demonstrated that for patients with diabetes mellitus (DM) and multivessel coronary disease (MVD), coronary artery bypass grafting (CABG) is superior to percutaneous coronary intervention with drug-eluting stents (PCI-DES) in reducing the rate of major adverse cardiovascular and cerebrovascular events after a median follow-up of 3.8 years. It is not known, however, whether CABG confers a survival benefit after an extended follow-up period. Objectives The purpose of this study was to evaluate the long-term survival of DM patients with MVD undergoing coronary revascularization in the FREEDOM trial. Methods The FREEDOM trial randomized 1,900 patients with DM and MVD to undergo either PCI with sirolimus-eluting or paclitaxel-eluting stents or CABG on a background of optimal medical therapy. After completion of the trial, enrolling centers and patients were invited to participate in the FREEDOM Follow-On study. Survival was evaluated using Kaplan-Meier analysis, and Cox proportional hazards models were used for subgroup and multivariate analyses. Results A total of 25 centers (of 140 original centers) agreed to participate in the FREEDOM Follow-On study and contributed a total of 943 patients (49.6% of the original cohort) with a median follow-up of 7.5 years (range 0 to 13.2 years). Of the 1,900 patients, there were 314 deaths during the entire follow-up period (204 deaths in the original trial and 110 deaths in the FREEDOM Follow-On). The all-cause mortality rate was significantly higher in the PCI-DES group than in the CABG group (24.3% [159 deaths] vs. 18.3% [112 deaths]; hazard ratio: 1.36; 95% confidence interval: 1.07 to 1.74; p = 0.01). Of the 943 patients with extended follow-up, the all-cause mortality rate was 23.7% (99 deaths) in the PCI-DES group and 18.7% (72 deaths) in the CABG group (hazard ratio: 1.32; 95% confidence interval: 0.97 to 1.78; p = 0.076). Conclusions In patients with DM and MVD, coronary revascularization with CABG leads to lower all-cause mortality than with PCI-DES in long-term follow-up. (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes [FREEDOM]; NCT00086450)
- Published
- 2019
12. SYNTAX Score in Patients With Diabetes Undergoing Coronary Revascularization in the FREEDOM Trial
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Flora S. Siami, Rodrigo Barbosa Esper, Lucas C. Godoy, Whady Hueb, Michael E. Farkouh, Valentin Fuster, John K. French, Expedito E. Ribeiro, Michael J. Domanski, Verghese Mathew, and Taye H. Hamza
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medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Hazard ratio ,Percutaneous coronary intervention ,030204 cardiovascular system & hematology ,Revascularization ,medicine.disease ,Confidence interval ,Coronary artery disease ,03 medical and health sciences ,surgical procedures, operative ,0302 clinical medicine ,Diabetes mellitus ,Internal medicine ,Conventional PCI ,medicine ,Cardiology ,cardiovascular diseases ,030212 general & internal medicine ,Myocardial infarction ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background Diabetes mellitus (DM) is associated with complex coronary artery disease (CAD), which in turn results in increased morbidity and mortality from cardiovascular disease. Objectives This study sought to evaluate the utility of SYNTAX score (SS) for predicting future cardiovascular events in patients with DM and complex CAD undergoing either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI). Methods The FREEDOM (Future REvascularization Evaluation in patients with Diabetes mellitus: Optimal management of Multivessel disease) trial randomized patients with DM and multivessel CAD to undergo either PCI with drug-eluting stents or CABG. The SS was calculated retrospectively by a core laboratory. The endpoint of hard cardiovascular events (HCE) was a composite of death from any cause, nonfatal myocardial infarction, and nonfatal stroke, while the endpoint of major adverse cardiac and cerebrovascular events (MACCE) was a composite of HCE and repeat revascularization. Results A total of 1,900 patients were randomized to PCI (n = 953) or CABG (n = 947). The SS was considered an independent predictor of 5-year MACCE (hazard ratio per unit of SS: 1.02; 95% confidence interval: 1.00 to 1.03; p = 0.014) and HCE (hazard ratio per unit of SS: 1.03; 95% confidence interval: 1.01 to 1.04; p = 0.002) in the PCI cohort, but not in the CABG group. There was a higher incidence of MACCE in PCI patients with low, intermediate, and high SS compared with those who underwent CABG (36.6% vs. 25.9%, p = 0.02; 43.9% vs. 26.8%, p Conclusions In DM patients with multivessel CAD, the complexity of CAD evaluated by the SS is an independent risk factor for MACCE and HCE only in patients undergoing PCI. The SS should not be utilized to guide the choice of coronary revascularization in patients with DM and multivessel CAD. (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes [FREEDOM]; NCT00086450)
- Published
- 2018
13. WBC alloimmunization: effects on the laboratory and clinical endpoints of therapeutic granulocyte transfusions
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Paul M. Ness, Ronald G. Strauss, Thomas H. Price, Jeffrey McCullough, Susan F. Assmann, Taye H. Hamza, and Ryan W. Harrison
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medicine.medical_specialty ,Immunology ,030204 cardiovascular system & hematology ,Granulocyte ,Neutropenia ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,White blood cell ,Clinical endpoint ,medicine ,Immunology and Allergy ,Seroconversion ,biology ,business.industry ,Hematology ,medicine.disease ,medicine.anatomical_structure ,biology.protein ,Transfusion therapy ,Antibody ,business ,030215 immunology - Abstract
Background Although the subject of many previous studies, the importance of white blood cell (WBC) alloimmunization in granulocyte transfusion therapy has not been settled. In this study, we report the results of the effects of WBC antibodies in the RING (Resolving Infection in Neutropenia with Granulocytes) study, a randomized controlled trial comparing the efficacy of daily granulocyte transfusion therapy plus antimicrobials versus antimicrobials alone; the primary outcome results have been published previously. Study design and methods One hundred fourteen subjects were enrolled in the study. Serum samples for WBC antibody determination were obtained from each subject at baseline and at 2 and 6 weeks. One hundred subjects had at least one antibody test result. Samples were tested for human leukocyte antigen (HLA) Class I and Class II antibodies as well as for granulocyte-specific antibodies using granulocyte agglutination and immunofluorescence techniques. All testing was performed at a central laboratory. Results Baseline WBC alloimmunization was modest, depending somewhat on the assay. Seroconversion during the study was slightly higher in the granulocyte transfusion arm, but the differences were not statistically significant. There was no demonstrable effect of the presence of alloimmunization on the primary outcome (survival and microbial response at 42 days), the occurrence of transfusion reactions (either overall or pulmonary), or posttransfusion neutrophil increments. Conclusion The presence or development of WBC antibodies had no demonstrable effect on any clinical aspect of granulocyte transfusion therapy. It appears that, at least in the patient population studied, there is no evidence suggesting need for concern about recipient WBC alloimmunization when prescribing granulocyte transfusions.
- Published
- 2018
14. Dual Antiplatelet Therapy Versus Aspirin Monotherapy in Diabetics With Multivessel Disease Undergoing CABG
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Sean van Diepen, Shaun G. Goodman, Valentin Fuster, Taye H. Hamza, Michael E. Farkouh, Subodh Verma, and F. Sandra Siami
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medicine.medical_specialty ,Aspirin ,Blood transfusion ,business.industry ,medicine.medical_treatment ,Hazard ratio ,030204 cardiovascular system & hematology ,medicine.disease ,Revascularization ,Clopidogrel ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Diabetes mellitus ,medicine ,Cardiology ,030212 general & internal medicine ,Myocardial infarction ,Cardiology and Cardiovascular Medicine ,business ,Stroke ,medicine.drug - Abstract
Background Clinical practice guidelines recommend post-operative dual antiplatelet therapy (DAPT) in patients who undergo coronary artery bypass grafting (CABG) following acute coronary syndromes (ACS). Objectives The authors have evaluated DAPT utilization rates and associated outcomes among post-CABG patients with diabetes. Methods In a post hoc, nonrandomized analysis from the FREEDOM (Future REvascularization Evaluation in patients with Diabetes mellitus: Optimal management of Multivessel disease) trial, we compared patients receiving DAPT (aspirin plus thienopyridine) and aspirin monotherapy at 30 days post-operatively. The primary outcome was the risk adjusted 5-year FREEDOM composite of all-cause mortality, nonfatal myocardial infarction, or stroke. Safety outcomes included major bleeding, blood transfusion, and hospitalization for bleeding. Results At 30 days post-CABG, 544 (68.4%) patients received DAPT and 251 (31.6%) patients received aspirin alone. The median (25th, 75th percentile) duration of clopidogrel therapy was 0.98 (0.23 to 1.91) years. There was no significant difference in the 5-year primary composite outcome between DAPT- and aspirin-treated patients (12.6% vs. 16.0%; adjusted hazard ratio [HR]: 0.83; 95% confidence interval [CI]: 0.54 to 1.27; p = 0.39). The 5-year primary composite outcomes were similar for patients receiving DAPT versus aspirin monotherapy respectively, in subgroups with pre-CABG ACSs (15.2% vs. 16.5%; HR: 1.06; 95% CI: 0.53 to 2.10; p = 0.88) and those with stable angina (11.6% vs. 15.8%; HR: 0.82; 95% CI: 0.50 to 1.343; p = 0.42). The composite outcomes of both treatment groups were also similar by SYNTAX score, duration of DAPT therapy, completeness of revascularization, and in off-pump CABG. No treatment-related differences in major bleeding (5.6% vs. 5.7%; HR: 1.00; 95% CI: 0.50 to 1.99; p = 0.99), blood transfusions (4.8% vs. 4.5%; HR: 1.09; 95% CI: 0.51 to 2.34; p = 0.82), or hospitalization for bleeding (2.6% vs. 3.3%; HR: 0.85; 95% CI: 0.34 to 2.17; p = 0.74) were observed between aspirin- and DAPT-treated patients, respectively. Conclusions The use of DAPT in patients with diabetes post-CABG in our cohort was high. Compared with aspirin monotherapy, no associated differences were observed in cardiovascular or bleeding outcomes, suggesting that routine use of DAPT may not be clinically warranted. (Future REvascularization Evaluation in patients with Diabetes mellitus: Optimal management of Multivessel disease [FREEDOM]; NCT00086450)
- Published
- 2017
15. Incidence, determinants and impact of acute kidney injury in patients with diabetes mellitus and multivessel disease undergoing coronary revascularization: Results from the FREEDOM trial
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Yaron Arbel, Valentin Fuster, Flora S. Siami, Taye H. Hamza, Usman Baber, and Michael E. Farkouh
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Male ,medicine.medical_specialty ,medicine.medical_treatment ,Comorbidity ,Coronary Artery Disease ,030204 cardiovascular system & hematology ,urologic and male genital diseases ,Revascularization ,Severity of Illness Index ,Coronary artery disease ,03 medical and health sciences ,0302 clinical medicine ,Percutaneous Coronary Intervention ,Risk Factors ,Internal medicine ,medicine ,Clinical endpoint ,Diabetes Mellitus ,Humans ,cardiovascular diseases ,030212 general & internal medicine ,Myocardial infarction ,Coronary Artery Bypass ,Correlation of Data ,Stroke ,business.industry ,Incidence ,Percutaneous coronary intervention ,Acute Kidney Injury ,Middle Aged ,medicine.disease ,female genital diseases and pregnancy complications ,Conventional PCI ,Cardiology ,Female ,Risk Adjustment ,Cardiology and Cardiovascular Medicine ,business ,Mace - Abstract
The incidence and prognostic significance of acute kidney injury (AKI) in patients with diabetes mellitus and multivessel coronary artery disease undergoing coronary revascularization is not well known. The current analysis included patients randomized to PCI vs. CABG as part of the FREEDOM trial. We sought to examine the impact of AKI and its predictors in diabetic patients with multivessel coronary artery disease undergoing PCI vs. CABG.We conducted a pre-specified subgroup analysis of the FREEDOM trial to examine the incidence, correlates and impact of AKI according to revascularization strategy. AKI predictors were identified using multivariable logistic regression and associations between AKI and outcomes were examined using Cox regression. The primary endpoint was the composite occurrence of all-cause death, stroke or myocardial infarction at 5 years of follow-up.KI occurred more frequently in patients following CABG (15.6%) compared with PCI (9.1%) (p 0.001). AKI was associated with a higher risk for major cardiovascular events (MACE) at 5 years (34.6% vs. 20.5%, p 0.001), an effect that remained large and significant irrespective of CABG (HR = 2.18 95% CI 1.44-3.31, p ≤0.001) or PCI (HR = 2.08 95% CI 1.35-3.21, p 0.0001). There was a non-significant interaction (p-value = 0.89) between the revascularization method and AKI, supporting that AKI is a significant risk factor in both revascularization methods.Although risk for AKI was higher in patients undergoing CABG, the impact of AKI on MACE was substantial irrespective of revascularization strategy. Preventive strategies to identify patients at risk for AKI are warranted to mitigate the long-term effects of this complication.
- Published
- 2018
16. Long-Term Survival Following Multivessel Revascularization in Patients With Diabetes: The FREEDOM Follow-On Study
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Michael E, Farkouh, Michael, Domanski, George D, Dangas, Lucas C, Godoy, Michael J, Mack, Flora S, Siami, Taye H, Hamza, Binita, Shah, Giulio G, Stefanini, Mandeep S, Sidhu, Jean-François, Tanguay, Krishnan, Ramanathan, Samin K, Sharma, John, French, Whady, Hueb, David J, Cohen, Valentin, Fuster, and Upendra, Kaul
- Subjects
Male ,Drug-Eluting Stents ,Coronary Artery Disease ,Kaplan-Meier Estimate ,Middle Aged ,Survival Rate ,Percutaneous Coronary Intervention ,Treatment Outcome ,Humans ,Female ,Coronary Artery Bypass ,Diabetic Angiopathies ,Aged ,Follow-Up Studies ,Proportional Hazards Models - Abstract
The FREEDOM (Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease) trial demonstrated that for patients with diabetes mellitus (DM) and multivessel coronary disease (MVD), coronary artery bypass grafting (CABG) is superior to percutaneous coronary intervention with drug-eluting stents (PCI-DES) in reducing the rate of major adverse cardiovascular and cerebrovascular events after a median follow-up of 3.8 years. It is not known, however, whether CABG confers a survival benefit after an extended follow-up period.The purpose of this study was to evaluate the long-term survival of DM patients with MVD undergoing coronary revascularization in the FREEDOM trial.The FREEDOM trial randomized 1,900 patients with DM and MVD to undergo either PCI with sirolimus-eluting or paclitaxel-eluting stents or CABG on a background of optimal medical therapy. After completion of the trial, enrolling centers and patients were invited to participate in the FREEDOM Follow-On study. Survival was evaluated using Kaplan-Meier analysis, and Cox proportional hazards models were used for subgroup and multivariate analyses.A total of 25 centers (of 140 original centers) agreed to participate in the FREEDOM Follow-On study and contributed a total of 943 patients (49.6% of the original cohort) with a median follow-up of 7.5 years (range 0 to 13.2 years). Of the 1,900 patients, there were 314 deaths during the entire follow-up period (204 deaths in the original trial and 110 deaths in the FREEDOM Follow-On). The all-cause mortality rate was significantly higher in the PCI-DES group than in the CABG group (24.3% [159 deaths] vs. 18.3% [112 deaths]; hazard ratio: 1.36; 95% confidence interval: 1.07 to 1.74; p = 0.01). Of the 943 patients with extended follow-up, the all-cause mortality rate was 23.7% (99 deaths) in the PCI-DES group and 18.7% (72 deaths) in the CABG group (hazard ratio: 1.32; 95% confidence interval: 0.97 to 1.78; p = 0.076).In patients with DM and MVD, coronary revascularization with CABG leads to lower all-cause mortality than with PCI-DES in long-term follow-up. (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes [FREEDOM]; NCT00086450).
- Published
- 2018
17. Response to 'Be alert to leukocyte antibodies when prescribing granulocyte transfusions'
- Author
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Jeffrey McCullough, Ronald G. Strauss, Paul M. Ness, Ryan W. Harrison, Thomas H. Price, Susan F. Assmann, and Taye H. Hamza
- Subjects
medicine.anatomical_structure ,biology ,business.industry ,Immunology ,medicine ,biology.protein ,Immunology and Allergy ,Hematology ,Granulocyte ,Antibody ,business - Published
- 2019
18. Efficacy of transfusion with granulocytes from G-CSF/dexamethasone–treated donors in neutropenic patients with infection
- Author
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Melissa M. Cushing, David F. Friedman, Janice G. McFarland, Samir Parekh, Jeffrey McCullough, Susan F. Assmann, Michael Boeckh, Ronald G. Strauss, Joseph E. Kiss, Karen E. King, Eliot C. Williams, Taye H. Hamza, Jo Anne H. Young, Paul M. Ness, W. Garrett Nichols, Jennifer Holter Chakrabarty, Steven R. Sloan, Bruce S. Sachais, Ryan W. Harrison, and Thomas H. Price
- Subjects
medicine.medical_specialty ,Neutropenia ,Blood transfusion ,medicine.medical_treatment ,Immunology ,Granulocyte ,Infections ,Biochemistry ,Dexamethasone ,law.invention ,Leukocyte Count ,Anti-Infective Agents ,Randomized controlled trial ,Inside BLOOD Commentary ,law ,Internal medicine ,Granulocyte Colony-Stimulating Factor ,medicine ,Humans ,Glucocorticoids ,business.industry ,Cell Biology ,Hematology ,medicine.disease ,Granulocyte colony-stimulating factor ,Leukocyte Transfusion ,Treatment Outcome ,medicine.anatomical_structure ,Absolute neutrophil count ,Transfusion therapy ,business ,Granulocytes ,medicine.drug - Abstract
High-dose granulocyte transfusion therapy has been available for 20 years, yet its clinical efficacy has never been conclusively demonstrated. We report here the results of RING (Resolving Infection in Neutropenia with Granulocytes), a multicenter randomized controlled trial designed to address this question. Eligible subjects were those with neutropenia (absolute neutrophil count500/μL) and proven/probable/presumed infection. Subjects were randomized to receive either (1) standard antimicrobial therapy or (2) standard antimicrobial therapy plus daily granulocyte transfusions from donors stimulated with granulocyte colony-stimulating factor (G-CSF) and dexamethasone. The primary end point was a composite of survival plus microbial response, at 42 days after randomization. Microbial response was determined by a blinded adjudication panel. Fifty-six subjects were randomized to the granulocyte arm and 58 to the control arm. Transfused subjects received a median of 5 transfusions. Mean transfusion dose was 54.9 × 10(9) granulocytes. Overall success rates were 42% and 43% for the granulocyte and control groups, respectively (P.99), and 49% and 41%, respectively, for subjects who received their assigned treatments (P = .64). Success rates for granulocyte and control arms did not differ within any infection type. In a post hoc analysis, subjects who received an average dose per transfusion of ≥0.6 × 10(9) granulocytes per kilogram tended to have better outcomes than those receiving a lower dose. In conclusion, there was no overall effect of granulocyte transfusion on the primary outcome, but because enrollment was half that planned, power to detect a true beneficial effect was low. RING was registered at www.clinicaltrials.gov as #NCT00627393.
- Published
- 2015
19. WBC alloimmunization: effects on the laboratory and clinical endpoints of therapeutic granulocyte transfusions
- Author
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Thomas H, Price, Jeffrey, McCullough, Ronald G, Strauss, Paul M, Ness, Taye H, Hamza, Ryan W, Harrison, and Susan F, Assmann
- Subjects
Adult ,Male ,Young Adult ,HLA Antigens ,Seroconversion ,Leukocytes ,Humans ,Transfusion Reaction ,Female ,Antibodies ,Granulocytes - Abstract
Although the subject of many previous studies, the importance of white blood cell (WBC) alloimmunization in granulocyte transfusion therapy has not been settled. In this study, we report the results of the effects of WBC antibodies in the RING (Resolving Infection in Neutropenia with Granulocytes) study, a randomized controlled trial comparing the efficacy of daily granulocyte transfusion therapy plus antimicrobials versus antimicrobials alone; the primary outcome results have been published previously.One hundred fourteen subjects were enrolled in the study. Serum samples for WBC antibody determination were obtained from each subject at baseline and at 2 and 6 weeks. One hundred subjects had at least one antibody test result. Samples were tested for human leukocyte antigen (HLA) Class I and Class II antibodies as well as for granulocyte-specific antibodies using granulocyte agglutination and immunofluorescence techniques. All testing was performed at a central laboratory.Baseline WBC alloimmunization was modest, depending somewhat on the assay. Seroconversion during the study was slightly higher in the granulocyte transfusion arm, but the differences were not statistically significant. There was no demonstrable effect of the presence of alloimmunization on the primary outcome (survival and microbial response at 42 days), the occurrence of transfusion reactions (either overall or pulmonary), or posttransfusion neutrophil increments.The presence or development of WBC antibodies had no demonstrable effect on any clinical aspect of granulocyte transfusion therapy. It appears that, at least in the patient population studied, there is no evidence suggesting need for concern about recipient WBC alloimmunization when prescribing granulocyte transfusions.
- Published
- 2017
20. Laboratory predictors of bleeding and the effect of platelet and RBC transfusions on bleeding outcomes in the PLADO trial
- Author
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Lynne Uhl, Susan F. Assmann, Taye H. Hamza, Terry Gernsheimer, Ryan W. Harrison, and Sherrill J. Slichter
- Subjects
Adult ,Blood Platelets ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Immunology ,Hemorrhage ,Platelet Transfusion ,030204 cardiovascular system & hematology ,Hematocrit ,Biochemistry ,Gastroenterology ,Models, Biological ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Platelet ,International Normalized Ratio ,Blood coagulation test ,Chemotherapy ,Hematology ,medicine.diagnostic_test ,business.industry ,Platelet Count ,Fibrinogen ,Cell Biology ,Odds ratio ,Middle Aged ,Surgery ,Platelet transfusion ,Treatment Outcome ,Female ,Partial Thromboplastin Time ,Blood Coagulation Tests ,business ,Erythrocyte Transfusion ,030215 immunology ,Partial thromboplastin time - Abstract
Bleeding remains a significant problem for many thrombocytopenic hematology/oncology patients in spite of platelet transfusions. Factors that might contribute to bleeding were analyzed for 16 320 patient-days on or after their first platelet transfusion in 1077 adult patients enrolled in the Platelet Dose (PLADO) trial. All patients had a greatly increased risk of bleeding at platelet counts of ≤5 × 109/L (odds ratio [OR], 3.1; 95% confidence interval [CI], 2.0-4.8) compared with platelet counts ≥81 × 109/L. Platelet counts between 6 × 109/L and 80 × 109/L were also associated with a somewhat elevated bleeding risk in patients receiving allogeneic stem cell transplants (SCTs) or chemotherapy but not in those undergoing autologous SCTs. Other significant laboratory predictors of bleeding were hematocrit ≤25% (OR, 1.29; 95% CI, 1.11-1.49), activated partial thromboplastin time (aPTT) 30 to ≤50 seconds (OR, 1.40; 95% CI, 1.08-1.81; P = .01), aPTT >50 seconds (OR, 2.34; 95% CI, 1.54-3.56), international normalized ratio (INR) 1.2 to 1.5 (OR, 1.46; 95% CI, 1.17-1.83), and INR >1.5 (OR, 2.05; 95% CI, 1.43-2.95). Transfusion of either platelets or red blood cells (RBCs) on days with bleeding was often not sufficient to change bleeding outcomes on the following day. Because bleeding occurred over a wide range of platelet counts among patients undergoing allogeneic SCT or chemotherapy and because platelet transfusions may not prevent bleeding, other risk factors may be involved. These may include low hematocrit and coagulation abnormalities. This trial was registered at www.clinicaltrials.gov as #NCT00128713.
- Published
- 2017
21. Comparative efficacy of coronary artery bypass surgery vs. percutaneous coronary intervention in patients with diabetes and multivessel coronary artery disease with or without chronic kidney disease
- Author
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Michael E. Farkouh, Taye H. Hamza, Yaron Arbel, Valentin Fuster, Roxana Mehran, George Dangas, Michael J. Mack, Usman Baber, and Paul Muntner
- Subjects
Male ,medicine.medical_specialty ,medicine.medical_treatment ,Coronary Artery Disease ,030204 cardiovascular system & hematology ,Revascularization ,Coronary artery disease ,03 medical and health sciences ,Coronary artery bypass surgery ,0302 clinical medicine ,Percutaneous Coronary Intervention ,Internal medicine ,medicine ,Diabetes Mellitus ,Humans ,cardiovascular diseases ,030212 general & internal medicine ,Myocardial infarction ,Coronary Artery Bypass ,Renal Insufficiency, Chronic ,Stroke ,business.industry ,Percutaneous coronary intervention ,Drug-Eluting Stents ,medicine.disease ,surgical procedures, operative ,Treatment Outcome ,Conventional PCI ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business ,Kidney disease - Abstract
Background The optimal method of coronary revascularization among patients with diabetes mellitus (DM) and multivessel coronary artery disease (CAD) complicated by chronic kidney disease (CKD) remains unknown. Purpose To examine the impact of coronary artery bypass surgery (CABG) vs. percutaneous coronary intervention (PCI) on cardiovascular outcomes in patients with diabetes with and without CKD. Methods We conducted an ‘as-treated’ subgroup analysis of the FREEDOM trial to examine the therapeutic efficacy of CABG vs. PCI among patients with DM stratified by the presence ( n = 451) or absence ( n = 1392) of CKD. We defined CKD as an estimated glomerular filtration rate (eGFR)
- Published
- 2016
22. A comprehensive analysis of deletions, multiplications, and copy number variations in PARK2
- Author
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Stewart A. Factor, Denise M. Kay, Haydeh Payami, Jennifer S. Montimurro, J. G. Nutt, Parvoneh Poorkaj, Lina M. Moses, C. Stevens, Alida Griffith, Gerard D. Schellenberg, Eric Molho, Taye H. Hamza, Thomas D. Bird, John W. Roberts, S. Zareparsi, Donald S. Higgins, S. T. Gancher, Cyrus P. Zabetian, and Ali Samii
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,DNA Copy Number Variations ,Ubiquitin-Protein Ligases ,Population ,Biology ,Bioinformatics ,medicine.disease_cause ,Statistics, Nonparametric ,Gene Frequency ,Reference Values ,Internal medicine ,medicine ,Humans ,Genetic Predisposition to Disease ,Genetic Testing ,Copy-number variation ,Age of Onset ,education ,Allele frequency ,Aged ,Sequence Deletion ,Genetic testing ,Aged, 80 and over ,Mutation ,education.field_of_study ,medicine.diagnostic_test ,Point mutation ,Age Factors ,Parkinson Disease ,Articles ,Odds ratio ,Middle Aged ,Female ,Neurology (clinical) ,Age of onset - Abstract
Objectives: To perform a comprehensive population genetic study of PARK2 . PARK2 mutations are associated with juvenile parkinsonism, Alzheimer disease, cancer, leprosy, and diabetes mellitus, yet ironically, there has been no comprehensive study of PARK2 in control subjects; and to resolve controversial association of PARK2 heterozygous mutations with Parkinson disease (PD) in a well-powered study. Methods: We studied 1,686 control subjects (mean age 66.1 ± 13.1 years) and 2,091 patients with PD (mean onset age 58.3 ± 12.1 years). We tested for PARK2 deletions/multiplications/copy number variations (CNV) using semiquantitative PCR and multiplex ligation-dependent probe amplification, and validated the mutations by real-time quantitative PCR. Subjects were tested for point mutations previously. Association with PD was tested as PARK2 main effect, and in combination with known PD risk factors: SNCA, MAPT, APOE , smoking, and coffee intake. Results: A total of 0.95% of control subjects and 0.86% of patients carried a heterozygous CNV mutation. CNV mutations found in 16 control subjects were all in exons 1–4, sparing exons that encode functionally critical protein domains. Thirteen patients had 2 CNV mutations, 5 had 1 CNV and 1 point mutation, and 18 had 1 CNV mutation. Mutations found in patients spanned exons 2–9. In whites, having 1 CNV was not associated with increased risk (odds ratio 1.05, p = 0.89) or earlier onset of PD (64.7 ± 8.6 heterozygous vs 58.5 ± 11.8 normal). Conclusions: This comprehensive population genetic study in control subjects fills the void for a PARK2 reference dataset. There is no compelling evidence for association of heterozygous PARK2 mutations, by themselves or in combination with known risk factors, with PD.
- Published
- 2010
23. Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson's disease
- Author
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Victoria I. Kusel, William K. Scott, Elizabeth W. Pugh, Randall V. Collura, Denise M. Kay, Taye H. Hamza, Alida Griffith, Kimberly F. Doheny, Haydeh Payami, Dora Yearout, Jennifer S. Montimurro, John W. Roberts, Justin Paschall, Alain Laederach, Stewart A. Factor, Ali Samii, John G. Nutt, Albert Tenesa, and Cyrus P. Zabetian
- Subjects
Adult ,Male ,Parkinson's disease ,Genetic Linkage ,Genome-wide association study ,Late onset ,Disease ,Human leukocyte antigen ,Biology ,Article ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Degenerative disease ,Meta-Analysis as Topic ,HLA Antigens ,Odds Ratio ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Age of Onset ,Aged ,030304 developmental biology ,Aged, 80 and over ,0303 health sciences ,Case-control study ,Genetic Variation ,Parkinson Disease ,Middle Aged ,medicine.disease ,Case-Control Studies ,Female ,Age of onset ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
Parkinson's disease is a common disorder that leads to motor and cognitive disability. We performed a genome-wide association study of 2,000 individuals with Parkinson's disease (cases) and 1,986 unaffected controls from the NeuroGenetics Research Consortium (NGRC)(1-5). We confirmed associations with SNCA(2,6-8) and MAPT(3,7-9), replicated an association with GAK9 (using data from the NGRC and a previous study(9), P = 3.2 x 10(-9)) and detected a new association with the HLA region (using data from the NGRC only, P = 2.9 x 10(-8)), which replicated in two datasets (meta-analysis P = 1.9 x 10(-10)). The HLA association was uniform across all genetic and environmental risk strata and was strong in sporadic (P = 5.5 x 10(-10)) and late-onset (P = 2.4 x 10(-8)) disease. The association peak we found was at rs3129882, a noncoding variant in HLA-DRA. Two studies have previously suggested that rs3129882 influences expression of HLA-DR and HLA-DQ(10,11). The brains of individuals with Parkinson's disease show upregulation of DR antigens and the presence of DR-positive reactive microglia(12), and nonsteroidal anti-inflammatory drugs reduce Parkinson's disease risk(4,13). The genetic association with HLA supports the involvement of the immune system in Parkinson's disease and offers new targets for drug development.
- Published
- 2010
24. Glutamate Receptor Gene GRIN2A, Coffee, and Parkinson Disease
- Author
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Haydeh Payami, Jeffrey M. Vance, Taye H. Hamza, Cyrus P. Zabetian, Stewart A. Factor, William K. Scott, and Erin M. Hill-Burns
- Subjects
DNA Replication ,Cancer Research ,lcsh:QH426-470 ,Genotype ,Denmark ,Genome-wide association study ,Disease ,Pharmacology ,Biology ,Coffee ,Polymorphism, Single Nucleotide ,Receptors, N-Methyl-D-Aspartate ,Formal Comment ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Caffeine ,Genetics ,Humans ,Allele ,Molecular Biology ,Gene ,Genetics (clinical) ,Ecology, Evolution, Behavior and Systematics ,030304 developmental biology ,0303 health sciences ,Smoking ,Glutamate receptor ,Parkinson Disease ,lcsh:Genetics ,chemistry ,Pharmacogenomics ,biology.protein ,GRIN2A ,Gene-Environment Interaction ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Published
- 2014
25. DUAL ANTI-PLATELET THERAPY IS NOT SUPERIOR TO ASPIRIN ALONE AFTER CORONARY ARTERY BYPASS IN DIABETIC PATIENTS WITH MULTI-VESSEL DISEASE: INSIGHTS FROM THE FREEDOM TRIAL
- Author
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Valentin Fuster, Michael E. Farkouh, Sean Van Diepen, Subodh Verma, Shaun G. Goodman, Taye H. Hamza, and F. Sandra Siami
- Subjects
medicine.medical_specialty ,Aspirin ,medicine.anatomical_structure ,business.industry ,Internal medicine ,Cardiology ,medicine ,Cardiology and Cardiovascular Medicine ,business ,Multi vessel disease ,Anti platelet ,Artery ,medicine.drug - Published
- 2016
26. Meta-analysis of Parkinson disease: Identification of a novel locus, RIT2
- Author
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Clemens R. Scherzer, William K. Scott, Caroline M. Tanner, Dmitri Krainc, Anita L. DeStefano, Karen Marder, Richard Mayeux, Tatiana Foroud, Kimberly F. Doheny, Owen A. Ross, Zbigniew K. Wszolek, Gary W. Beecham, Stewart A. Factor, Haydeh Payami, Bradley T. Hyman, David Simon, Albert Y. Hung, Nathan Pankratz, Ted M. Dawson, Eden R. Martin, Adrian J. Ivinson, Taye H. Hamza, Jeffery M. Vance, Jeanne C. Latourelle, Cyrus P. Zabetian, Lorraine N. Clark, and Richard H. Myers
- Subjects
Genetics ,Single-nucleotide polymorphism ,Locus (genetics) ,Genome-wide association study ,Nerve Tissue Proteins ,Parkinson Disease ,Human leukocyte antigen ,Odds ratio ,Biology ,Polymorphism, Single Nucleotide ,Article ,Neurology ,Chromosome 18 ,Genetic Loci ,Genotype ,SNP ,Humans ,Neurology (clinical) ,Genome-Wide Association Study ,Glycoproteins ,Monomeric GTP-Binding Proteins - Abstract
Objective: Genome-wide association (GWAS) methods have identified genes contributing to Parkinson’s disease (PD); we sought to identify additional genes associated with PD susceptibility. Methods: A 2-stage design was used. First, individual level genotypic data from 5 recent PD GWAS (Discovery Sample: 4,238 PD cases and 4,239 controls) were combined. Following imputation, a logistic regression model was employed in each dataset to test for association with PD susceptibility and results from each dataset were metaanalyzed. Second, 768 single-nucleotide polymorphisms (SNPs) were genotyped in an independent Replication Sample (3,738 cases and 2,111 controls). Results: Genome-wide significance was reached for SNPs in SNCA (rs356165; G: odds ratio [OR] ¼ 1.37; p ¼ 9.3 � 10 � 21 ), MAPT (rs242559; C: OR ¼ 0.78; p ¼ 1.5 � 10 � 10 ), GAK/DGKQ (rs11248051; T: OR ¼ 1.35; p ¼ 8.2 � 10 � 9 / rs11248060; T: OR ¼ 1.35; p ¼ 2.0 � 10 � 9 ), and the human leukocyte antigen (HLA) region (rs3129882; A: OR ¼ 0.83; p ¼ 1.2 � 10 � 8 ), which were previously reported. The Replication Sample confirmed the associations with SNCA, MAPT, and the HLA region and also with GBA (E326K; OR ¼ 1.71; p ¼ 5 � 10 � 8 Combined Sample) (N370; OR ¼ 3.08; p ¼ 7 � 10 � 5 Replication sample). A novel PD susceptibility locus, RIT2, on chromosome 18 (rs12456492; p ¼ 5 � 10 � 5 Discovery Sample; p ¼ 1.52 � 10 � 7 Replication sample; p ¼ 2 � 10 � 10 Combined Sample) was replicated. Conditional analyses within each of the replicated regions identified distinct SNP associations within GBA and SNCA, suggesting that there may be multiple risk alleles within these genes. Interpretation: We identified a novel PD susceptibility locus, RIT2, replicated several previously identified loci, and identified more than 1 risk allele within SNCA and GBA. ANN NEUROL 2012;71:370–384
- Published
- 2012
27. Genome-Wide Gene-Environment Study Identifies Glutamate Receptor Gene GRIN2A as a Parkinson's Disease Modifier Gene via Interaction with Coffee
- Author
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Jianjun Gao, William K. Scott, Albert Tenesa, Denise M. Kay, Yvette Bordelon, Pinky Agarwal, Silviu Alin Bacanu, Patricia Sheehan, Jeffery M. Vance, Beate Ritz, John G. Nutt, Cyrus P. Zabetian, Erin M. Hill-Burns, Ali Samii, Shannon L. Rhodes, Liyong Wang, Stewart A. Factor, Muthukrishnan Eaaswarkhanth, Haydeh Payami, Jennifer S. Montimurro, Taye H. Hamza, John W. Roberts, Yikyung Park, Victoria I. Kusel, Kenneth S. Kendler, Dora Yearout, and Honglei Chen
- Subjects
Male ,Cancer Research ,Genotype ,Neurogenetics ,Single-nucleotide polymorphism ,Genome-wide association study ,QH426-470 ,Bioinformatics ,Coffee ,Polymorphism, Single Nucleotide ,Receptors, N-Methyl-D-Aspartate ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Genetics ,SNP ,Humans ,Genetic Predisposition to Disease ,Genetics(clinical) ,Gene–environment interaction ,10. No inequality ,Biology ,Molecular Biology ,Genetics (clinical) ,Ecology, Evolution, Behavior and Systematics ,030304 developmental biology ,0303 health sciences ,biology ,Genome, Human ,Parkinson Disease ,3. Good health ,Case-Control Studies ,biology.protein ,Medicine ,GRIN2A ,Female ,Gene-Environment Interaction ,030217 neurology & neurosurgery ,Pharmacogenetics ,Research Article ,Genome-Wide Association Study - Abstract
Our aim was to identify genes that influence the inverse association of coffee with the risk of developing Parkinson's disease (PD). We used genome-wide genotype data and lifetime caffeinated-coffee-consumption data on 1,458 persons with PD and 931 without PD from the NeuroGenetics Research Consortium (NGRC), and we performed a genome-wide association and interaction study (GWAIS), testing each SNP's main-effect plus its interaction with coffee, adjusting for sex, age, and two principal components. We then stratified subjects as heavy or light coffee-drinkers and performed genome-wide association study (GWAS) in each group. We replicated the most significant SNP. Finally, we imputed the NGRC dataset, increasing genomic coverage to examine the region of interest in detail. The primary analyses (GWAIS, GWAS, Replication) were performed using genotyped data. In GWAIS, the most significant signal came from rs4998386 and the neighboring SNPs in GRIN2A. GRIN2A encodes an NMDA-glutamate-receptor subunit and regulates excitatory neurotransmission in the brain. Achieving P2df = 10−6, GRIN2A surpassed all known PD susceptibility genes in significance in the GWAIS. In stratified GWAS, the GRIN2A signal was present in heavy coffee-drinkers (OR = 0.43; P = 6×10−7) but not in light coffee-drinkers. The a priori Replication hypothesis that “Among heavy coffee-drinkers, rs4998386_T carriers have lower PD risk than rs4998386_CC carriers” was confirmed: ORReplication = 0.59, PReplication = 10−3; ORPooled = 0.51, PPooled = 7×10−8. Compared to light coffee-drinkers with rs4998386_CC genotype, heavy coffee-drinkers with rs4998386_CC genotype had 18% lower risk (P = 3×10−3), whereas heavy coffee-drinkers with rs4998386_TC genotype had 59% lower risk (P = 6×10−13). Imputation revealed a block of SNPs that achieved P2df, Author Summary Parkinson's disease (PD), like most common disorders, involves interactions between genetic make-up and environmental exposures that are unique to each individual. Caffeinated-coffee consumption may protect some people from developing PD, although not all benefit equally. In a genome-wide search, we discovered that variations in the glutamate-receptor gene GRIN2A modulate the risk of developing PD in heavy coffee drinkers. The study was hypothesis-free, that is, we cast a net across the entire genome allowing statistical significance to point us to a genetic variant, regardless of whether it fell in a genomic desert or an important gene. Fortuitously, the most significant finding was in a well-known gene, GRIN2A, which regulates brain signals that control movement and behavior. Our finding is important for three reasons: First, it is a proof of concept that studying genes and environment on the whole-genome scale is feasible, and this approach can identify important genes that are missed when environmental exposures are ignored. Second, the knowledge of interaction between GRIN2A, which is involved in neurotransmission in the brain, and caffeine, which is an adenosine-A2A-receptor antagonist, will stimulate new research towards understanding the cause and progression of PD. Third, the results may lead to personalized prevention of and treatment for PD.
- Published
- 2011
28. Random effects meta-analysis of event outcome in the framework of the generalized linear mixed model with applications in sparse data
- Author
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Taye H. Hamza, Pinar Ozdemir, and Theo Stijnen
- Subjects
Statistics and Probability ,Epidemiology ,Normal Distribution ,Continuity correction ,Hemorrhage ,Logistic regression ,Generalized linear mixed model ,Disease-Free Survival ,Normal distribution ,meta-analysis random effects rare events non-central hypergeometric distribution binomial distribution approximate likelihood exact likelihood bivariate meta-analysis multivariate meta-analysis network meta-analysis central venous catheters clinical-trials regression variance ,Meta-Analysis as Topic ,Statistics ,Rare events ,Odds Ratio ,Humans ,Computer Simulation ,Poisson Distribution ,Diagnostic Techniques and Procedures ,Mathematics ,Endarterectomy, Carotid ,Likelihood Functions ,Models, Statistical ,Incidence ,Linear model ,Bayes Theorem ,Cerebral Infarction ,Random effects model ,Fibrosis ,Binomial Distribution ,Standard error ,Treatment Outcome ,Multivariate Analysis ,Linear Models ,Controlled Clinical Trials as Topic ,Algorithms - Abstract
We consider random effects meta-analysis where the outcome variable is the occurrence of some event of interest. The data structures handled are where one has one or more groups in each study, and in each group either the number of subjects with and without the event, or the number of events and the total duration of follow-up is available. Traditionally, the meta-analysis follows the summary measures approach based on the estimates of the outcome measure(s) and the corresponding standard error(s). This approach assumes an approximate normal within-study likelihood and treats the standard errors as known. This approach has several potential disadvantages, such as not accounting for the standard errors being estimated, not accounting for correlation between the estimate and the standard error, the use of an (arbitrary) continuity correction in case of zero events, and the normal approximation being bad in studies with few events. We show that these problems can be overcome in most cases occurring in practice by replacing the approximate normal within-study likelihood by the appropriate exact likelihood. This leads to a generalized linear mixed model that can be fitted in standard statistical software. For instance, in the case of odds ratio meta-analysis, one can use the non-central hypergeometric distribution likelihood leading to mixed-effects conditional logistic regression. For incidence rate ratio meta-analysis, it leads to random effects logistic regression with an offset variable. We also present bivariate and multivariate extensions. We present a number of examples, especially with rare events, among which an example of network meta-analysis. Copyright (C) 2010 John Wiley & Sons, Ltd.
- Published
- 2010
29. Multivariate random effects meta-analysis of diagnostic tests with multiple thresholds
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Taye H. Hamza, Hans C. van Houwelingen, Theo Stijnen, Lidia R. Arends, and Epidemiology
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Multivariate statistics ,Multivariate analysis ,Computer science ,Threshold limit value ,Epidemiology ,Differential Threshold ,Health Informatics ,Bivariate analysis ,computer.software_genre ,Meta-Analysis as Topic ,Research article ,Statistics ,Methods ,Humans ,Sensitivity (control systems) ,Diagnostic Techniques and Procedures ,lcsh:R5-920 ,Models, Statistical ,Random effects model ,ROC Curve ,Meta-analysis ,Multivariate Analysis ,Table (database) ,Data mining ,lcsh:Medicine (General) ,computer - Abstract
Background Bivariate random effects meta-analysis of diagnostic tests is becoming a well established approach when studies present one two-by-two table or one pair of sensitivity and specificity. When studies present multiple thresholds for test positivity, usually meta-analysts reduce the data to a two-by-two table or take one threshold value at a time and apply the well developed meta-analytic approaches. However, this approach does not fully exploit the data. Methods In this paper we generalize the bivariate random effects approach to the situation where test results are presented with k thresholds for test positivity, resulting in a 2 by (k+1) table per study. The model can be fitted with standard likelihood procedures in statistical packages such as SAS (Proc NLMIXED). We follow a multivariate random effects approach; i.e., we assume that each study estimates a study specific ROC curve that can be viewed as randomly sampled from the population of all ROC curves of such studies. In contrast to the bivariate case, where nothing can be said about the shape of study specific ROC curves without additional untestable assumptions, the multivariate model can be used to describe study specific ROC curves. The models are easily extended with study level covariates. Results The method is illustrated using published meta-analysis data. The SAS NLMIXED syntax is given in the appendix. Conclusion We conclude that the multivariate random effects meta-analysis approach is an appropriate and convenient framework to meta-analyse studies with multiple threshold without losing any information by dichotomizing the test results.
- Published
- 2009
30. Meta-analysis of diagnostic studies: a comparison of random intercept, normal-normal, and binomial-normal bivariate summary ROC approaches
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Taye H. Hamza, Johannes B. Reitsma, Theo Stijnen, Epidemiology, APH - Amsterdam Public Health, and Epidemiology and Data Science
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Ligaments ,Models, Statistical ,Mean squared error ,Receiver operating characteristic ,Diagnostic Tests, Routine ,Health Policy ,Anterior Cruciate Ligament Injuries ,Variance (accounting) ,Bivariate analysis ,Residual ,Magnetic Resonance Imaging ,Sensitivity and Specificity ,Tibial Meniscus Injuries ,Binomial distribution ,Normal distribution ,Meta-Analysis as Topic ,ROC Curve ,Sample size determination ,Data Interpretation, Statistical ,Statistics ,Humans ,Wounds and Injuries ,Posterior Cruciate Ligament ,Mathematics - Abstract
Background . The authors compared 3 recently introduced refinements of the Littenberg and Moses summary receiver operating characteristic (ROC) method for pooling studies of a diagnostic test: the random intercept (RI) linear meta-regression model, the approximate normal distribution (normal-normal [NN] model), and the binomial distribution (binomial-normal [BN] model). Methods . Using data from a published meta-analysis of magnetic resonance imaging of the menisci and cruciate ligaments, the authors varied the overall sensitivity and specificity, the between-studies variance, the within-study sample size, and the number of studies to evaluate the performances of the 3 methods in a simulation study. The parameters to be compared are the associated intercept, slope, and residual variance, using bias, mean squared error, and coverage probabilities. Results . The BN method always gave unbiased estimates of the intercept and slope parameter. The coverage probabilities were also reasonably acceptable, unless the number of studies was very small. In contrast, the RI and NN methods could produce large biases with poor coverage probabilities, especially when sample sizes of individual studies were small or when sensitivities or specificities were close to 1. Although this was rare in the simulations, the bivariate methods can suffer from nonconvergence mostly due to the correlation being close to ± 1. Conclusion . The binomial-normal model performed better than the other recently introduced methods for meta-analysis of data from studies of test performance.
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- 2008
31. Bivariate random effects meta-analysis of ROC curves
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Majanka H. Heijenbrok-Kal, Lidia R. Arends, M. G. Myriam Hunink, Theo Stijnen, J.C. van Houwelingen, Taye H. Hamza, Child and Adolescent Psychiatry / Psychology, Epidemiology, and Radiology & Nuclear Medicine
- Subjects
Models, Statistical ,Receiver operating characteristic ,Diagnostic Tests, Routine ,Health Policy ,Diagnostic test ,Bivariate analysis ,Random effects model ,computer.software_genre ,Meta-Analysis as Topic ,ROC Curve ,Meta-analysis ,Data Interpretation, Statistical ,Statistics ,Humans ,Data mining ,computer ,Mathematics - Abstract
Meta-analysis of receiver operating characteristic (ROC)-curve data is often done with fixed-effects models, which suffer many shortcomings. Some random-effects models have been proposed to execute a meta-analysis of ROC-curve data, but these models are not often used in practice. Straightforward modeling techniques for multivariate random-effects meta-analysis of ROC-curve data are needed. The 1st aim of this article is to present a practical method that addresses the drawbacks of the fixedeffects summary ROC (SROC) method of Littenberg and Moses. Sensitivities and specificities are analyzed simultaneously using a bivariate random-effects model. The 2nd aim is to show that other SROC curves can also be derived from the bivariate model through different characterizations of the estimated bivariate normal distribution. Thereby the authors show that the bivariate random-effects approach not only extends the SROC approach but also provides a unifying framework for other approaches. The authors bring the statistical meta-analysis of ROC-curve data back into a framework of relatively standard multivariate meta-analysis with random effects. The analyses were carried out using the software package SAS (Proc NLMIXED).
- Published
- 2008
32. The binomial distribution of meta-analysis was preferred to model within-study variability
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Theo Stijnen, Hans C. van Houwelingen, Taye H. Hamza, and Epidemiology
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Models, Statistical ,Epidemiology ,Coverage probability ,Contrast (statistics) ,Variance (accounting) ,Random effects model ,Data set ,Normal distribution ,Binomial distribution ,Binomial Distribution ,Meta-Analysis as Topic ,Alzheimer Disease ,Fluorodeoxyglucose F18 ,Sample size determination ,Data Interpretation, Statistical ,Positron-Emission Tomography ,Statistics ,Econometrics ,Humans ,Radiopharmaceuticals ,Diagnostic Techniques and Procedures ,Mathematics - Abstract
Objective: When studies report proportions such as sensitivity or specificity, it is customary to meta-analyze them using the DerSimonian and Laird random effects model. This method approximates the within-study variability of the proportion by a normal distribution, which may lead to bias for several reasons. Alternatively an exact likelihood approach based on the binomial within-study distribution can be used. This method can easily be performed in standard statistical packages. We investigate the performance of the standard method and the alternative approach. Study Design and Setting: We compare the two approaches through a simulation study, in terms of bias, mean-squared error, and coverage probabilities. We varied the size of the overall sensitivity or specificity, the between-studies variance, the within-study sample sizes, and the number of studies. The methods are illustrated using a published meta-analysis data set. Results: The exact likelihood approach performs always better than the approximate approach and gives unbiased estimates. The coverage probability, in particular for the profile likelihood, is also reasonably acceptable. In contrast, the approximate approach gives huge bias with very poor coverage probability in many cases. Conclusion: The exact likelihood approach is the method of preference and should be used whenever feasible. (C) 2008 Elsevier Inc. All rights reserved.
- Published
- 2008
33. Associating explanatory variables with summary receiver operating characteristic curves in diagnostic meta-analysis
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Majanka H. Heijenbrok-Kal, Taye H. Hamza, Hans C. van Houwelingen, and Theo Stijnen
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Models, Statistical ,Receiver operating characteristic ,Epidemiology ,Design matrix ,Bivariate analysis ,Coronary Artery Disease ,Covariance ,Random effects model ,Sensitivity and Specificity ,Meta-Analysis as Topic ,ROC Curve ,Data Interpretation, Statistical ,Statistics ,Linear regression ,Covariate ,Econometrics ,Humans ,Regression diagnostic ,Diagnostic Techniques and Procedures ,Mathematics ,Ultrasonography - Abstract
Objective: To show how the bivariate random effects meta-analysis model can be used to study the relation between the explanatory variables and the performance of diagnostic tests as characterized by a summary receiver operating characteristic curve (SROCC). Study Design and Setting: The subject is discussed by means of a data example in which sensitivity and specificity are available for 149 studies on one of three tests for the diagnosis of coronary artery disease. The focus is on comparing SROCCs between different tests adjusted for potential confounders, but the methods can be applied much more generally. Results: Different types of SROCCs can be calculated. The influence of explanatory variables on an SROCC is an ensemble of sensitivity and specificity regression coefficients and covariance parameters. The regression coefficients of the SROCC are estimated and tested, and the percentage explained variability is determined. Under certain assumptions, the SROCCs of different covariate values do not cross. If these are fulfilled, it is much easier to describe the influence of explanatory variables. Conclusions can depend on the type of SROCC. Conclusion: The bivariate random effects meta-analysis model is an appropriate and convenient framework to investigate the effect of covariates on the performance of diagnostic tests as measured by SROCCs.
- Published
- 2007
34. An attempt to replicate interaction between coffee andCYP1A2gene in connection to Parkinson’s disease
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Stewart A. Factor, Haydeh Payami, Cyrus P. Zabetian, Erin M. Hill-Burns, and Taye H. Hamza
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Genetics ,Inverse Association ,business.industry ,Neurogenetics ,Disease ,Replicate ,Correlation ,Neurology ,Covariate ,Genotype ,Medicine ,Neurology (clinical) ,business ,Genotyping ,Demography - Abstract
Popat et al. [1] recently reported evidence for interaction between Cytochrome P450 1A2 (CYP1A2) genotype and coffee on the risk of developing Parkinson’s disease (PD). This finding is particularly intriguing because caffeine consumption is inversely associated with risk of developing PD, and CYP1A2 is involved in metabolism of caffeine. Popat et al also suggested that the coffee–PD association was strongest among homozygous carriers of the slow-metabolizer CYP1A2_ rs762551_CC genotype. In an accompanying editorial [2] Mellick and Ross point out that caffeine-metabolism genes have not been found to associate with PD in genome-wide studies. Were the genes missed because coffee and interaction were not in the analytical model? Considering the high potential significance of this observation, we attempted to replicate it using 1458 persons with PD and 931 controls from the NeuroGenetics Research Consortium (NGRC), all Caucasian of European Origin, with detailed life-time coffee consumption data [3] and genotyped using Illumina HumanOmni1-Quad_v1-0_B genotyping array [4]. rs2472304 was genotyped, rs762551 and rs2470890 were imputed with high accuracy (imputation-information-score>0.98) [5]. The study was approved by Institutional Review Boards. We first tested interaction under the same model as Popat et al. adjusting for age and sex while stratifying coffee-consumption as ever/never (Table 1). In addition, we reanalyzed the data with coffee stratified as high/low (defined at median), which is a more sensitive measure for NGRC due to high coffee-consumption and few non-coffee-drinkers in NGRC. We also tried models where principal components and smoking were added as covariates. As noted by Mellick and Ross [3] both population structure (genetic mixtures) and smoking could confound these results. Inclusion of principal components corrects for population structure in European-Americans due to Jewish/non-Jewish ancestry and European country-of-origin [4]. Inclusion of smoking as a covariate helps assess if results are affected by the correlation between smoking and coffee-drinking, and the inverse association of smoking with PD [3]. Unfortunately, we did not replicate the reported interactions under any of the models, nor did we find a stronger PD-coffee association among slow-metabolizers (Table 1). Table 1 Test results for SNPxCoffee interaction and genotype-specific PD-coffee association
- Published
- 2011
35. P2.067 Resolving mode-of-inheritance and association of PRKN with PD in a comprehensive sequence and copy-number-variation (CNV) analysis of 3800 subjects
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Donald S. Higgins, Taye H. Hamza, Denise M. Kay, Jennifer S. Montimurro, Lina M. Moses, C. Stevens, Cyrus P. Zabetian, G. Schellenberg, S. Zareparsi, Stewart A. Factor, H. Payami, and John G. Nutt
- Subjects
Genetics ,Inheritance (object-oriented programming) ,Neurology ,Association (object-oriented programming) ,Mode (statistics) ,Neurology (clinical) ,Copy-number variation ,Geriatrics and Gerontology ,Biology ,Sequence (medicine) - Published
- 2009
36. Meta-analysis of binary data using profile likelihood. Dankmar Böhning, Ronny Kuhnert and Sasivimol Rattanasiri, Chapman & Hall/CRC, Boca Raton, 2008. No. of pages: 208. Price: $79.95. ISBN: 978-1-58488-630-3
- Author
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Taye H. Hamza
- Subjects
Statistics and Probability ,Discrete mathematics ,Epidemiology ,Binary data ,Mathematics - Published
- 2009
37. P2.110 Evidence for association of high-dose levodopa therapy with intellectual and psychiatric complications of Parkinson's disease
- Author
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Eric Molho, Donald S. Higgins, D. Pratt, Jennifer S. Montimurro, Stewart A. Factor, Taye H. Hamza, H. Payami, and Ami Rosen
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medicine.medical_specialty ,Parkinson's disease ,Neurology ,business.industry ,Medicine ,Levodopa therapy ,Neurology (clinical) ,Geriatrics and Gerontology ,business ,Psychiatry ,medicine.disease ,Association (psychology) - Published
- 2009
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