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2.  Progression of coronary atherosclerosis in African-American patients 
Background
African-Americans with coronary artery disease (CAD) demonstrate worse clinical outcomes than Caucasians. While this is partly due to a lack of accessibility to established therapies, the mechanisms underlying this difference remain to be elucidated. We aimed to characterize the progression of coronary atherosclerosis in African-Americans with CAD.
Methods
3,479 patients with CAD underwent serial intravascular ultrasound (IVUS) imaging to evaluate atheroma progression in 7 clinical trials of anti-atherosclerotic therapies. Risk factor control and atheroma progression were compared between African-Americans (n=170) and Caucasians (n=3,309).
Results
African-Americans were more likely to be female (51.8% vs. 28.1%, P<0.001), have a higher body mass index (32.8±6.0 vs. 31.3±5.8 kg/m2, P=0.002) and greater history of hypertension (85.9% vs. 78.8%, P=0.02), diabetes (41.8% vs. 30.6%, P=0.002) and stroke (12.9% vs. 3.0%, P<0.001). Despite a high use of anti-atherosclerotic medications (93% statin, 89% aspirin, 79% β-blocker, 52% ACE inhibitor), African-Americans demonstrated higher levels of LDL-C (2.4±0.7 vs. 2.2±0.7 mmol/L, P=0.006), CRP (2.9 vs. 2.0 mg/dL, P<0.001) and systolic blood pressure (133±15 vs. 129±13 mmHg, P<0.001) at follow-up. There was no significant difference in atheroma volume at baseline (189.0±82.2 vs. 191.6±83.3 mm3, P=0.82) between two groups. Serial evaluation demonstrated a greater increase in atheroma volume in African-Americans (0.51±2.1 vs. –3.1±1.7 mm3, P=0.01). This difference persisted with propensity matching accounting for differences in risk factor control (0.1±2.1 vs. –3.7±1.7 mm3, P=0.02).
Conclusions
African-Americans with CAD achieve less optimal risk factor control and greater atheroma progression. These findings support the need for more intensive risk factor modification in African-Americans.
doi:10.3978/j.issn.2223-3652.2013.08.05
PMCID: PMC3839202  PMID: 24282765
African-American; coronary atherosclerosis; intravascular ultrasound (IVUS)
3.  ADAPT: The Wrong Way to Stop a Clinical Trial 
PLoS Clinical Trials  2006;1(7):e35.
doi:10.1371/journal.pctr.0010035
PMCID: PMC1851725  PMID: 17111045
4.  Bariatric Surgery versus Intensive Medical Therapy in Obese Patients with Diabetes 
The New England Journal of Medicine  2012;366(17):1567-1576.
BACKGROUND
Observational studies have shown improvement in patients with type 2 diabetes mellitus after bariatric surgery.
METHODS
In this randomized, nonblinded, single-center trial, we evaluated the efficacy of intensive medical therapy alone versus medical therapy plus Roux-en-Y gastric bypass or sleeve gastrectomy in 150 obese patients with uncontrolled type 2 diabetes. The mean (±SD) age of the patients was 49 ± 8 years, and 66% were women. The average glycated hemoglobin level was 9.2 ± 1.5%. The primary end point was the proportion of patients with a glycated hemoglobin level of 6.0% or less 12 months after treatment.
RESULTS
Of the 150 patients, 93% completed 12 months of follow-up. The proportion of patients with the primary end point was 12% (5 of 41 patients) in the medical-therapy group versus 42% (21 of 50 patients) in the gastric-bypass group (P = 0.002) and 37% (18 of 49 patients) in the sleeve-gastrectomy group (P = 0.008). Glycemic control improved in all three groups, with a mean glycated hemoglobin level of 7.5 ± 1.8% in the medical-therapy group, 6.4 ± 0.9% in the gastric-bypass group (P<0.001), and 6.6 ± 1.0% in the sleeve-gastrectomy group (P = 0.003). Weight loss was greater in the gastric-bypass group and sleeve-gastrectomy group (−29.4 ± 9.0 kg and −25.1 ± 8.5 kg, respectively) than in the medical-therapy group (−5.4 ± 8.0 kg) (P<0.001 for both comparisons). The use of drugs to lower glucose, lipid, and blood-pressure levels decreased significantly after both surgical procedures but increased in patients receiving medical therapy only. The index for homeostasis model assessment of insulin resistance (HOMA-IR) improved significantly after bariatric surgery. Four patients underwent reoperation. There were no deaths or life-threatening complications.
CONCLUSIONS
In obese patients with uncontrolled type 2 diabetes, 12 months of medical therapy plus bariatric surgery achieved glycemic control in significantly more patients than medical therapy alone. Further study will be necessary to assess the durability of these results. (Funded by Ethicon Endo-Surgery and others; ClinicalTrials.gov number, NCT00432809.)
doi:10.1056/NEJMoa1200225
PMCID: PMC3372918  PMID: 22449319
5.  Risk Prediction with Serial Myeloperoxidase Monitoring in Patients with Acute Chest Pain 
Clinical Chemistry  2011;57(12):1762-1770.
BACKGROUND
Although myeloperoxidase (MPO) monitoring is predictive for cardiovascular outcomes in suspected acute coronary syndromes, the value of serial testing is unknown.
METHODS
We investigated the relationship between serial MPO concentrations in 490 individuals with acute chest pain and incident major adverse cardiac events (MACE) during 6 months of follow-up. We measured MPO with the CardioMPO assay, and cardiac troponin I (cTnI), with the Abbott Architect assay.
RESULTS
Plasma MPO concentrations during the first 16 h were higher in individuals who experienced MACE. Higher MPO quartiles predicted a greater likelihood of 6-month MACE at baseline [OR (95% CI), 2.4 (1.4 – 4.1), P = 0.001 for highest vs lowest quartile] and all subsequent time points, with strongest predictive ability found in 16-h postbaseline samples [9.9 (4.7–20.9), P < 0.001 for highest vs lowest quartile]. MPO was predictive for MACE among individuals whose cTnI remained within reference intervals (<0.028 μg/L). The lowest rate of missed cases was found when MPO was <640 pmol/L at baseline and all other time points. Serial MPO monitoring predicted MACE risk better than baseline MPO measurements alone (c statistic 0.813 vs 0.602; P = 0.002), including in individuals whose cTnI remained within reference intervals (c statistic 0.903; P = 0.009). Combined serial cTnI and MPO testing improved accuracy for predicting 6-month MACE, reduced the number of missed MACE events from cTnI testing alone, and improved risk classification in 26.1% of patients.
CONCLUSIONS
MPO concentrations are predictive of outcome up to 16 h after presentation with chest pain and predict events missed by cTnI testing, supporting a potential role in rapid patient triage.
doi:10.1373/clinchem.2011.166827
PMCID: PMC3335294  PMID: 21940659
6.  Trial Publication after Registration in ClinicalTrials.Gov: A Cross-Sectional Analysis 
PLoS Medicine  2009;6(9):e1000144.
Joseph Ross and colleagues examine publication rates of clinical trials and find low rates of publication even following registration in Clinicaltrials.gov.
Background
ClinicalTrials.gov is a publicly accessible, Internet-based registry of clinical trials managed by the US National Library of Medicine that has the potential to address selective trial publication. Our objectives were to examine completeness of registration within ClinicalTrials.gov and to determine the extent and correlates of selective publication.
Methods and Findings
We examined reporting of registration information among a cross-section of trials that had been registered at ClinicalTrials.gov after December 31, 1999 and updated as having been completed by June 8, 2007, excluding phase I trials. We then determined publication status among a random 10% subsample by searching MEDLINE using a systematic protocol, after excluding trials completed after December 31, 2005 to allow at least 2 y for publication following completion. Among the full sample of completed trials (n = 7,515), nearly 100% reported all data elements mandated by ClinicalTrials.gov, such as intervention and sponsorship. Optional data element reporting varied, with 53% reporting trial end date, 66% reporting primary outcome, and 87% reporting trial start date. Among the 10% subsample, less than half (311 of 677, 46%) of trials were published, among which 96 (31%) provided a citation within ClinicalTrials.gov of a publication describing trial results. Trials primarily sponsored by industry (40%, 144 of 357) were less likely to be published when compared with nonindustry/nongovernment sponsored trials (56%, 110 of 198; p<0.001), but there was no significant difference when compared with government sponsored trials (47%, 57 of 122; p = 0.22). Among trials that reported an end date, 75 of 123 (61%) completed prior to 2004, 50 of 96 (52%) completed during 2004, and 62 of 149 (42%) completed during 2005 were published (p = 0.006).
Conclusions
Reporting of optional data elements varied and publication rates among completed trials registered within ClinicalTrials.gov were low. Without greater attention to reporting of all data elements, the potential for ClinicalTrials.gov to address selective publication of clinical trials will be limited.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
People assume that whenever they are ill, health care professionals will make sure they get the best available treatment. But how do clinicians know which treatment is most appropriate? In the past, clinicians used their own experience to make treatment decisions. Nowadays, they rely on evidence-based medicine—the systematic review and appraisal of the results of clinical trials, studies that investigate the efficacy and safety of medical interventions in people. However, evidence-based medicine can only be effective if all the results from clinical trials are published promptly in medical journals. Unfortunately, the results of trials in which a new drug did not perform better than existing drugs or in which it had unwanted side effects often remain unpublished or only appear in the public domain many years after the drug has been approved for clinical use by the US Food and Drug Administration (FDA) and other governmental bodies.
Why Was This Study Done?
The extent of this “selective” publication, which can impair evidence-based clinical practice, remains unclear but is thought to be substantial. In this study, the researchers investigate the problem of selective publication by systematically examining the extent of publication of the results of trials registered in ClinicalTrials.gov, a Web-based registry of US and international clinical trials. ClinicalTrials.gov was established in 2000 by the US National Library of Medicine in response to the 1997 FDA Modernization Act. This act required preregistration of all trials of new drugs to provide the public with information about trials in which they might be able to participate. Mandatory data elements for registration in ClinicalTrials.gov initially included the trial's title, the condition studied in the trial, the trial design, and the intervention studied. In September 2007, the FDA Amendments Act expanded the mandatory requirements for registration in ClinicalTrials.gov by making it necessary, for example, to report the trial start date and to report primary and secondary outcomes (the effect of the intervention on predefined clinical measurements) in the registry within 2 years of trial completion.
What Did the Researchers Do and Find?
The researchers identified 7,515 trials that were registered within ClinicalTrials.gov after December 31, 1999 (excluding phase I, safety trials), and whose record indicated trial completion by June 8, 2007. Most of these trials reported all the mandatory data elements that were required by ClinicalTrials.gov before the FDA Amendments Act but reporting of optional data elements was less complete. For example, only two-thirds of the trials reported their primary outcome. Next, the researchers randomly selected 10% of the trials and, after excluding trials whose completion date was after December 31, 2005 (to allow at least two years for publication), determined the publication status of this subsample by systematically searching MEDLINE (an online database of articles published in selected medical and scientific journals). Fewer than half of the trials in the subsample had been published, and the citation for only a third of these publications had been entered into ClinicalTrials.gov. Only 40% of industry-sponsored trials had been published compared to 56% of nonindustry/nongovernment-sponsored trials, a difference that is unlikely to have occurred by chance. Finally, 61% of trials with a completion date before 2004 had been published, but only 42% of trials completed during 2005 had been published.
What Do These Findings Mean?
These findings indicate that, over the period studied, critical trial information was not included in the ClinicalTrials.gov registry. The FDA Amendments Act should remedy some of these shortcomings but only if the accuracy and completeness of the information in ClinicalTrials.gov is carefully monitored. These findings also reveal that registration in ClinicalTrials.gov does not guarantee that trial results will appear in a timely manner in the scientific literature. However, they do not address the reasons for selective publication (which may be, in part, because it is harder to publish negative results than positive results), and they are potentially limited by the methods used to discover whether trial results had been published. Nevertheless, these findings suggest that the FDA, trial sponsors, and the scientific community all need to make a firm commitment to minimize the selective publication of trial results to ensure that patients and clinicians have access to the information they need to make fully informed treatment decisions.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000144.
PLoS Medicine recently published two related articles on selected publication by Ida Sim and colleagues and by Lisa Bero and colleagues and an editorial discussing the FDA Amendments Act
ClinicalTrials.gov provides information about the US National Institutes of Health clinical trial registry, including background information about clinical trials, and a fact sheet detailing the requirements of the FDA Amendments Act 2007 for trial registration
The US Food and Drug Administration provides further information about drug approval in the US for consumers and health care professionals
doi:10.1371/journal.pmed.1000144
PMCID: PMC2728480  PMID: 19901971
7.  An Intravascular Ultrasound Analysis in Women Experiencing Chest Pain in the Absence of Obstructive Coronary Artery Disease 
Aims
Using intravascular ultrasound (IVUS), we sought to characterize coronary morphology in women with chest pain without major epicardial obstructive coronary artery disease (CAD). We have previously observed an unexpectedly high rate of adverse outcomes among women with chest pain and normal or insignificant obstructive CAD. Information about the presence and characteristics of coronary atherosclerosis in these women could provide insight into the mechanisms related to increased risk, as well as improved diagnosis, prevention, and treatment.
Methods
Women (n=100) with suspected ischemia without obstructive CAD (>50% stenosis) underwent IVUS of a left coronary segment with measurements by a core lab masked to clinical and angiographic findings.
Results
Angiograhic core lab analysis found 69.6% of patients had no (≤20%) and 30.4% had minimal (20–<50%) CAD. IVUS segmental images were interpretable by the core lab in 92 women, with 19 (21%) having no atherosclerosis (intimal-medial thickness <0.5 mm). In the remaining 73 women (79%), percent atheroma volume was 27±8% and mean maximum plaque thickness was 0.53±0.22 mm. Thirty-eight women with atherosclerosis (53%) had >30% of interrogated vessel involved. The average vessel involvement was 40%, and the maximum plaque thickness was 1.27 mm. The number of risk factors strongly correlated with percent atheroma volume (r=0.53, p<0.0001) and percent vessel involvement (r=0.51, p<0.0001), with the strongest independent predictor of both being age. Remodeling was assessed in 59/73 women (81%), and 73% had evidence of positive remodeling.
Conclusions
In symptomatic women without significant luminal obstructive CAD, we observed a very high prevalence of atherosclerosis with positive remodeling and preserved lumen size. These findings may help explain increased risk and emphasize need for improved diagnostic and treatment options for women with concealed CAD.
doi:10.1111/j.1540-8183.2010.00598.x
PMCID: PMC3019081  PMID: 21029178
chest pain in women; intravascular ultrasound; atherosclerosis; coronary artery disease

Results 1-7 (7)