Review and Analysis of Publication Trends over Three Decades in Three High Impact Medicine Journals.

CONTEXT: Over the past three decades, industry sponsored research expanded in the United States. Financial incentives can lead to potential conflicts of interest (COI) resulting in underreporting of negative study results. OBJECTIVE: We hypothesized that over the three decades, there would be an increase in: a) reporting of conflict of interest and source of funding; b) percentage of randomized control trials c) number of patients per study and d) industry funding. DATA SOURCES AND STUDY SELECTION: Original articles published in three calendar years (1988, 1998, and 2008) in The Lancet, New England Journal of Medicine and Journal of American Medical Association were collected. DATA EXTRACTION: Studies were reviewed and investigational design categorized as prospective and retrospective clinical trials. Prospective trials were categorized into randomized or non-randomized and single-center or multi-center trials. Retrospective trials were categorized as registries, meta-analyses and other studies, mostly comprising of case reports or series. Study outcomes were categorized as positive or negative depending on whether the pre-specified hypothesis was met. Financial disclosures were researched for financial relationships and profit status, and accordingly categorized as government, non-profit or industry sponsored. Studies were assessed for reporting COI. RESULTS: 1,671 original articles were included in this analysis. Total number of published studies decreased by 17% from 1988 to 2008. Over 20 year period, the proportion of prospective randomized trials increased from 22 to 46% (p < 0.0001); whereas the proportion of prospective non-randomized trials decreased from 59% to 27% (p < 0.001). There was an increase in the percentage of prospective randomized multi-center trials from 11% to 41% (p < 0.001). Conversely, there was a reduction in non-randomized single-center trials from 47% to 10% (p < 0.001). Proportion of government funded studies remained constant, whereas industry funded studies more than doubled (17% to 40%; p < 0.0001). The number of studies with negative results more than doubled (10% to 22%; p<0.0001). While lack of funding disclosure decreased from 35% to 7%, COI reporting increased from 2% to 84% (p < 0.0001). CONCLUSION: Improved reporting of COI, clarity in financial sponsorship, increased publication of negative results in the setting of larger and better designed clinical trials represents a positive step forward in the scientific publications, despite the higher percentage of industry funded studies.

Risks and complications of coronary angiography: a comprehensive review.

Coronary angiography and heart catheterization are invaluable tests for the detection and quantification of coronary artery disease, identification of valvular and other structural abnormalities, and measurement of hemodynamic parameters. The risks and complications associated with these procedures relate to the patient's concomitant conditions and to the skill and judgment of the operator. In this review, we examine in detail the major complications associated with invasive cardiac procedures and provide the reader with a comprehensive bibliography for advanced reading.

Enhancing the diagnostic performance of troponins in the acute care setting.

BACKGROUND: Current guidelines define cardiac troponin I (TnI) as an indicator of necrosis when the concentration exceeds the 99% upper limit of a healthy reference population, a reference value near the assay's lowest detectable level. We assessed the utility of a modified TnI cutoff point derived from a population at low risk for coronary artery disease (CAD) and evaluated its utility in determining acute myocardial infarction (MI). METHODS: A modified TnI cutoff point was derived by the receiver operating characteristic (ROC) curve from 737 consecutive patients who underwent serial TnI measurements for exclusion of MI. Creatinine kinase isoenzyme MB (CK-MB) evolutionary change was used to define MI. The new derived cutoff point was validated using another subset of 320 patients who were evaluated for MI. RESULTS: ROC-derived TnI cutoff point (A) was 0.65 µg/L, and its performance was compared to the recommended cutoff point ([B] 0.15 µg/L). Cutoff point A had greater specificity (94.5% vs. 86.9%, p < 0.001) but slightly lower sensitivity (96.5% vs. 100%, p < 0.01). Cutoff point A provided significantly greater positive predictive value (PPV) for MI (74.1% vs. 55.5%, p < 0.0001) and fewer false-positive errors, while preserving comparable negative predictive value (NPV) (98.9% vs. 100%). CONCLUSION: A higher cutoff point derived from a reference population of patients at low risk for CAD may improve the TnI performance assay. The PPV for diagnosis of MI was significantly higher and false-positive values were fewer without affecting the NPV. The more reliable diagnosis of MI may have resulted, which, in turn, may have significant clinical and economic implications.

Utility of brain natriuretic peptide as a predictor of atrial fibrillation after cardiac operations.

BACKGROUND: Atrial fibrillation (AF) occurs frequently after coronary bypass grafting and valve operations. Brain natriuretic peptide (BNP) has been shown to predict recurrence of AF in congestive heart failure. It is a potential biomarker for preoperative risk stratification for development of AF in at-risk patients. METHODS: A total of 398 consecutive patients were prospectively evaluated for new-onset AF after heart operations. Patients with a history of AF and presence of permanent pacemaker were excluded. BNP levels were measured before and immediately after the operation. RESULTS: AF occurred in 20%. AF was more likely to develop in patients who were older, who underwent valve operations, had a lower ejection fraction, and a larger left atrial size. Preoperative exposure to statins (62% vs 43%, p < 0.01) and angiotensin inhibitors (60% vs 45%, p = 0.02) was more common in patients without AF. BNP values were insignificantly higher preoperatively (361 vs 302 mg/dL, p = 0.3) and postoperatively (312 vs. 229 mg/dL, p = 0.15) in patients with AF. Multivariate logistic analysis showed that older age (odds ratio [OR], 3.1, 95% confidence interval [CI], 1.7 to 5.6), lower ejection fraction (OR, 2.0; 95% CI, 1.2 to 3.3), larger left atrial size (OR, 3.1; 95% CI, 1.9 to 4.9), and nonuse of angiotensin inhibitors (OR, 2.3; 95% CI, 1.1 to 4.8) were independently associated with AF. CONCLUSIONS: This study does not support use of BNP for prediction of AF. Age, low ejection fraction, large left atrial size, and nonuse of angiotensin blocking agents were found to be significant predictors of AF development.

Use of nesiritide in Ebstein's anomaly.

A rare case of a 77-year-old man with congestive heart failure due to a previously diagnosed condition of Ebstein's anomaly is presented. Unique to the present case is the treatment of New York Heart Association class IV congestive heart failure associated with Ebstein's anomaly with nesiritide.

Fiber size, type, and myosin heavy chain content in rhesus hindlimb muscles after 2 weeks at 2 G.

BACKGROUND: Fiber atrophy and an increase in the percentage of fast fibers have been observed in Rhesus leg muscles after spaceflight. HYPOTHESIS: Hypergravity will result in muscle fiber hypertrophy and an increase in the percentage of slow fibers. METHODS: Open muscle biopsies were obtained from Rhesus soleus, medial gastrocnemius (MG), and tibialis anterior (TA) muscles before and after 14 d of centrifugation (2 G) and in time-matched controls. Cage activity levels were measured by telemetry. RESULTS: Based on monoclonal antibody binding for myosin heavy chains (MHC), the fastest region of soleus contained a higher proportion of type I+II (27 vs. 13%) and had a tendency for a lower proportion of type I (38 vs. 61%, p = 0.10) fibers after than before centrifugation. There was a higher proportion of type I+II fibers in post- vs. pre-2 G (10 vs. 0.6%) MG biopsies. Fiber type distribution and MHC composition were unaffected in the TA. Overall, mean fiber sizes were unaffected by centrifugation. Average cage activity levels were 36% lower during than before 2 G. CONCLUSIONS: Our hypothesis was rejected. The changes in the proportion of fibers expressing type I MHC are the reverse of that expected with chronic loading of extensors and, paradoxically, are similar to changes observed with chronic unloading, such as occurs during spaceflight, in this primate model. The data are consistent with the observed decrease in total daily activity levels.