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Work 1-6 of 6

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Article

Trends in Consent for Clinical Trials in Cardiovascular Disease.

by Louis A. Kerkhoff; Javed Butler; Anita A. Kelkar; Supriya Shore; Candace D. Speight; Louisa K. Wall; Neal Dickert Jr

2016

Subjects
  • Health Sciences, General
  • Health Sciences, Medicine and Surgery
  • Health Sciences, Epidemiology
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Abstract:Close

BACKGROUND: Cardiovascular clinical trials depend on patient enrollment. Enrollment rates appear inadequate, but little is known about how frequently patients accept or decline offers of enrollment. The objective of this study was to assess trends and predictors of patient acceptance of offers to enroll in clinical trials for cardiovascular disease. METHODS AND RESULTS: We utilized an established database containing all randomized, controlled trials (n=1224) in cardiovascular disease published between 2001 and 2012 in the 8 highest-impact general medical and cardiology journals. Studies were eligible if the number of patients approached and number of patients declining enrollment could be ascertained from published materials. All studies were screened for eligibility. Each eligible study was reviewed by 3 co-authors. All discrepancies were resolved by the group. The main outcome was acceptance rate, defined as the number of patients enrolled divided by the number patients who were eligible and approached. Only 21.7% (n=266) of studies provided information sufficient to assess patient enrollment and refusals. The median acceptance rate across trials was 83.2%. Significant predictors of higher enrollment included: enrollment in the acute setting (P=0.031); geographical region (P<0.001 for group); and trial sponsorship (P=0.006 for group). CONCLUSIONS: Rates of reporting data sufficient to calculate acceptance rates are low. This compromises the ability to identify drivers of low enrollment and assess trial generalizability. However, the high rates of acceptance observed suggest that factors other than patients' decisions may be the primary drivers of declining rates of trial enrollment.

Article

Plasma stromal cell-derived factor 1 alpha/CXCL12 level predicts long-term adverse cardiovascular outcomes in patients with coronary artery disease

by Nima Ghasemzadeh; Abdul Wahab Hritani; Christine De Staercke; Danny Eapen; Emir Veledar; Hatem Al Kassem; Mohamed Khayata; Abarmard Zafari; Laurence Sperling; Craig Hooper; Laura Vaccarino; Kreton Mavromatis; Arshed Quyyumi

2015

Subjects
  • Health Sciences, Epidemiology
  • Health Sciences, Medicine and Surgery
  • Health Sciences, General
  • File Download
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Objective: Stromal derived factor-1α/CXCL12 is a chemoattractant responsible for homing of progenitor cells to ischemic tissues. We aimed to investigate the association of plasma CXCL12 with long-term cardiovascular outcomes in patients with coronary artery disease (CAD). Methods: 785 patients aged: 63±12 undergoing coronary angiography were independently enrolled into discovery (N=186) and replication (N=599) cohorts. Baseline levels of plasma CXCL12 were measured using Quantikine CXCL12 ELISA assay (R&D systems). Patients were followed for cardiovascular death and/or myocardial infarction (MI) for a mean of 2.6yrs. Cox proportional hazard was used to determine independent predictors of cardiovascular death/MI. Results: The incidence of cardiovascular death/MI was 13% (N=99). High CXCL12 level based on best discriminatory threshold derived from the ROC analysis predicted risk of cardiovascular death/MI (HR=4.81, p=1×10-6) independent of traditional risk factors in the pooled cohort. Addition of CXCL12 to a baseline model was associated with a significant improvement in c-statistic (AUC: 0.67-0.73, p=0.03). Addition of CXCL12 was associated with correct risk reclassification of 40% of events and 10.5% of non-events. Similarly for the outcome of cardiovascular death, the addition of the CXCL12 to the baseline model was associated with correct reclassification of 20.7% of events and 9% of non-events. These results were replicated in two independent cohorts. Conclusion: Plasma CXCL12 level is a strong independent predictor of adverse cardiovascular outcomes in patients with CAD and improves risk reclassification.

Article

Autoantibodies as biomarkers for the prediction of neuropsychiatric events in systemic lupus erythematosus

by J G Hanly; M B Urowitz; L Su; S-C Bae; C Gordon; A Clarke; S Bernatsky; A Vasudevan; D Isenberg; A Rahman; D J Wallace; P R Fortin; D Gladman; J Romero-Diaz; J Sanchez-Guerrero; M A Dooley; I Bruce; K Steinsson; M Khamashta; S Manzi; R Ramsey-Goldman; G Sturfelt; O Nived; R van Vollenhoven; M Ramos-Casals; C Aranow; M Mackay; K Kalunian; G S Alarcón; B J Fessler; G Ruiz-Irastorza; M Petri; Sung Lim; D Kamen; C Peschken; V Farewell; K Thompson; C Theriault; J T Merrill

2011

Subjects
  • Health Sciences, General
  • Health Sciences, Epidemiology
  • Health Sciences, Medicine and Surgery
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Objective: Neuropsychiatric events occur unpredictably in systemic lupus erythematosus (SLE) and most biomarker associations remain to be prospectively validated. This study examined a disease inception cohort of 1047 SLE patients to determine which autoantibodies at enrolment predicted subsequent neuropsychiatric events. Methods: Patients with a recent SLE diagnosis were assessed prospectively for up to 10 years for neuropsychiatric events using the American College of Rheumatology case definitions. Decision rules of graded stringency determined whether neuropsychiatric events were attributable to SLE. Associations between the first neuropsychiatric event and baseline autoantibodies (lupus anticoagulant (LA), anticardiolipin, anti- β2 glycoprotein-I, anti-ribosomal P and anti-NR2 glutamate receptor) were tested by Cox proportional hazards regression. Results: Disease duration at enrolment was 5.4±4.2 months, follow-up was 3.6±2.6 years. Patients were 89.1% female with mean (±SD) age 35.2±13.7 years. 495/1047 (47.3%) developed one or more neuropsychiatric event (total 917 events). Neuropsychiatric events attributed to SLE were 15.4% (model A) and 28.2% (model B). At enrolment 21.9% of patients had LA, 13.4% anticardiolipin, 15.1% anti-β2 glycoprotein-I, 9.2% anti-ribosomal P and 13.7% anti-NR2 antibodies. LA at baseline was associated with subsequent intracranial thrombosis (total n=22) attributed to SLE (model B) (HR 2.54, 95% CI 1.08 to 5.94). Anti-ribosomal P antibody was associated with subsequent psychosis (total n=14) attributed to SLE (model B) (HR 3.92, 95% CI 1.23 to 12.5, p=0.02). Other autoantibodies did not predict neuropsychiatric events. Conclusion: In a prospective study of 1047 recently diagnosed SLE patients, LA and anti-ribosomal P antibodies are associated with an increased future risk of intracranial thrombosis and lupus psychosis, respectively.

Article

Novel Biomarker of Oxidative Stress Is Associated With Risk of Death in Patients With Coronary Artery Disease

by Riyaz S. Patel; Nima Ghasemzadeh; Danny Eapen; Salman Sher; Shawn Arshad; Yi-An Ko; Emir Veledar; Habib Samady; Abarmard Zafari; Laurence Sperling; Laura Vaccarino; Dean Jones; Arshed Quyyumi

2016

Subjects
  • Health Sciences, Medicine and Surgery
  • Health Sciences, Epidemiology
  • Health Sciences, General
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BACKGROUND—: Free radical scavengers have failed to improve patient outcomes promoting the concept that clinically important oxidative stress (OS) may be mediated by alternative mechanisms. We sought to examine the association of emerging aminothiol markers of non-free radical mediated oxidative stress with clinical outcomes. METHODS AND RESULTS—: Plasma levels of reduced (cysteine and glutathione) and oxidized (cystine and glutathione disulphide) aminothiols were quantified by high performance liquid chromatography in 1411 patients undergoing coronary angiography (mean age 63 years, male 66%). All patients were followed for a mean of 4.7±2.1 years for the primary outcome of all-cause death (n=247). Levels of cystine (oxidized) and glutathione (reduced) were associated with risk of death (p<0.001 both) before and after adjustment for covariates. High cystine and low glutathione levels (=+1 SD & <-1 SD respectively) were associated with higher mortality (adjusted HR 1.63 (95% CI 1.19-2.21; HR 2.19 (95% CI 1.50-3.19), respectively) compared to those outside these thresholds. Furthermore, the ratio of cystine/glutathione was also significantly associated with mortality (adjusted HR 1.92 (95% CI 1.39-2.64) and was independent of and additive to hs-CRP level. Similar associations were found for other outcomes of cardiovascular death and combined death and myocardial infarction. CONCLUSIONS—: A high burden of OS, quantified by the plasma aminothiols, cystine, glutathione and their ratio is associated with mortality in patients with CAD, a finding that is independent of and additive to the inflammatory burden. Importantly, this data supports the emerging role of non-free radical biology in driving clinically important oxidative stress.

Article

Cardiovascular events prior to or early after diagnosis of systemic lupus erythematosus in the systemic lupus international collaborating clinics cohort.

by M B Urowitz; D D Gladman; N M Anderson; J Su; J Romero-Diaz; S C Bae; P R Fortin; J Sanchez-Guerrero; A Clarke; S Bernatsky; C Gordon; J G Hanly; D J Wallace; D Isenberg; A Rahman; J Merrill; E Ginzler; G S Alarcón; B F Fessler; M Petri; I N Bruce; M Khamashta; C Aranow; M Dooley; S Manzi; R Ramsey-Goldman; G Sturfelt; O Nived; K Steinsson; A Zoma; G Ruiz-Irastorza; Sung Lim; K C Kalunian; M Ỉnanç; R van Vollenhoven; M Ramos-Casals; D L Kamen; S Jacobsen; C Peschken; A Askanase; T Stoll

2016

Subjects
  • Health Sciences, Epidemiology
  • Health Sciences, General
  • Health Sciences, Medicine and Surgery
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OBJECTIVE: To describe the frequency of myocardial infarction (MI) prior to the diagnosis of systemic lupus erythematosus (SLE) and within the first 2 years of follow-up. METHODS: The systemic lupus international collaborating clinics (SLICC) atherosclerosis inception cohort enters patients within 15 months of SLE diagnosis. MIs were reported and attributed on a specialised vascular event form. MIs were confirmed by one or more of the following: abnormal ECG, typical or atypical symptoms with ECG abnormalities and elevated enzymes (≥2 times upper limit of normal), or abnormal stress test, echocardiogram, nuclear scan or angiogram. Descriptive statistics were used. RESULTS: 31 of 1848 patients who entered the cohort had an MI. Of those, 23 patients had an MI prior to SLE diagnosis or within the first 2 years of disease. Of the 23 patients studied, 60.9% were female, 78.3% were Caucasian, 8.7% black, 8.7% Hispanic and 4.3% other. The mean age at SLE diagnosis was 52.5±15.0 years. Of the 23 MIs that occurred, 16 MIs occurred at a mean of 6.1±7.0 years prior to diagnosis and 7 occurred within the first 2 years of follow-up. Risk factors associated with early MI in univariate analysis are male sex, Caucasian, older age at diagnosis, hypertension, hypercholesterolaemia, family history of MI and smoking. In multivariate analysis only age (OR=1.06 95% CI 1.03 to 1.09), hypertension (OR=5.01, 95% CI 1.38 to 18.23), hypercholesterolaemia (OR=4.43, 95% CI 1.51 to 12.99) and smoking (OR=7.50, 95% CI 2.38 to 23.57) remained significant risk factors. CONCLUSIONS: In some patients with lupus, MI may develop even before the diagnosis of SLE or shortly thereafter, suggesting that there may be a link between autoimmune inflammation and atherosclerosis.

Article

Calcium Supplementation Increases Blood Creatinine Concentration in a Randomized Controlled Trial

by Elizabeth L. Barry; Leila A. Mott; Michal L. Melamed; Judith R. Rees; Anastasia Ivanova; Robert S. Sandler; Dennis J. Ahnen; Robert S. Bresalier; Robert W. Summers; Roberd Bostick; John A. Baron

2014

Subjects
  • Health Sciences, Epidemiology
  • Health Sciences, Medicine and Surgery
  • Health Sciences, General
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Background Calcium supplements are widely used among older adults for osteoporosis prevention and treatment. However, their effect on creatinine levels and kidney function has not been well studied. Methods We investigated the effect of calcium supplementation on blood creatinine concentration in a randomized controlled trial of colorectal adenoma chemoprevention conducted between 2004–2013 at 11 clinical centers in the United States. Healthy participants (N = 1,675) aged 45–75 with a history of colorectal adenoma were assigned to daily supplementation with calcium (1200 mg, as carbonate), vitamin D3 (1000 IU), both, or placebo for three or five years. Changes in blood creatinine and total calcium concentration were measured after one year of treatment and multiple linear regression was used to estimate effects on creatinine concentrations. Results After one year of treatment, blood creatinine was 0.013±0.006 mg/dL higher on average among participants randomized to calcium compared to placebo after adjustment for other determinants of creatinine (P = 0.03). However, the effect of calcium treatment appeared to be larger among participants who consumed the most alcohol (2–6 drinks/day) or whose estimated glomerular filtration rate (eGFR) was less than 60 ml/min/1.73 m2 at baseline. The effect of calcium treatment on creatinine was only partially mediated by a concomitant increase in blood total calcium concentration and was independent of randomized vitamin D treatment. There did not appear to be further increases in creatinine after the first year of calcium treatment. Conclusions Among healthy adults participating in a randomized clinical trial, daily supplementation with 1200 mg of elemental calcium caused a small increase in blood creatinine. If confirmed, this finding may have implications for clinical and public health recommendations for calcium supplementation.
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