- Email: [email protected]
Reporting in randomized trials published in International Journal of Cardiology in 2011 compared to the recommendations made in CONSORT 2010
208
Letters to the Editor
Reporting in randomized trials published in International Journal of Cardiology in 2011 compared to the recommendations made in CONSORT 2010 Hong-Lin Chen a, Kun Liu b,⁎ a b
Nantong University, Qi Xiu Road 19# Nantong City, Jiangsu Province, 226001, PR China Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Xi Si Road 20# Nantong City, Jiangsu Province, 226001, PR China
a r t i c l e
i n f o
Article history: Received 21 March 2012 Received in revised form 8 May 2012 Accepted 8 June 2012 Available online 25 June 2012 Keywords: Reporting quality Randomized controlled trials CONSORT statement
Since its modest beginning in 1981, the International Journal of Cardiology (IJC) has progressed to become one of the most-recognized journals in the field of cardiology. The 2010 impact factor in the Science Citation Index (SCI) is 6.802, which has risen 6-fold in the last decade. The journal aims to present all aspects of cardiovascular medicine of relevance to the clinician from genes to populations. Randomized controlled trials (RCTs) are the standard method for the evaluation of treatments and technologies in clinical medicine. It has published many RCTs in the IJC. Inadequate trial design and inadequate reporting for RCTs are associated with biased estimates of effect, and incomplete descriptions of important methodological details in RCT publications make it difficult to assess the quality of the design, conduct, and analysis of the trial and limit readers' ability to interpret the results. The Consolidated Standards of Reporting Trials (CONSORT) statement provides a standardized framework to help authors prepare reports of their trial findings in a complete and transparent manner. The aim of this study was to assess quality of reporting of trial methodology and outcomes in RCTs published in IJC based on the CONSORT Statement, and find where improvements were required for this journal. We identified studies that were classified by PubMed as randomized clinical trials and were published between January 2011 and December 2009. The specific search terms were as follows: “Journal of Cardiology” [Jour] AND Randomized Controlled Trial [ptyp] AND (“2011/1/1” [Date — Publication]: “2011/12/31” [Date — Publication]). Articles were included in the analysis if they met the following criteria: (1) the article was original article of full-length publication, not editorials, letters to the editor, reviews, case reports. or notifications of meetings and courses.; (2) the study design was a RCT, not a cohort or case -control study. The eligible trials were analyzed for the presence or absence of 9 major items relevant to methodology quality criteria from the most recent CONSORT 2010 statement. [1] These items represent the elements of study design and reporting that are most useful for the assessment of bias and validity. Quality criteria, listed with the corresponding item number from the 2010 CONSORT checklist, were as follows. (1) 7a How sample size was determined; (2) 8a method used to generate the random allocation sequence; (3) 8b type of randomization; details of any restriction (such as blocking and block size); (4) 9 allocation concealment; mechanism used to implement the random allocation sequence (such as sequentially numbered containers), describing any steps taken to conceal the sequence until interventions were assigned; (5) 10 who generated the random allocation sequence, who enrolled participants, and who assigned participants to interven⁎ Corresponding author. E-mail address: [email protected] (K. Liu).
tions; (6) 11a if done, who was blinded after assignment to interventions (for example, participants, care providers, those assessing outcomes) and how (7) 15 A table showing baseline demographic and clinical characteristics for each group; (8) 16 for each group, number of participants (denominator) included in each analysis and whether the analysis was by original assigned groups (intention-to-treat analysis); (9) 18 results of any other analyses performed, including subgroup analyses and adjusted analyses, distinguishing pre-specified from exploratory. The CONSORT 2010 statement is list in the appendix. We assigned a ‘Yes’ or ‘No’ answer to each item according to whether the author had reported it or not. Two independent reviewers evaluated the included reports. Any differences in evaluation between the reviewers were discussed and resolved. Frequencies were reported as percentages. Fig. 1 shows the process of selecting study articles. A total of 40 potentially eligible citations were identified from the initial search, of which 12 citations were excluded because those were not full-length original articles, but letters to the editor. Among the remaining 28 articles [2–29], 4 were excluded because they were cohort studies [6,7,9,12], and 4 additional non randomized controlled trials [5,10,19,24] were also excluded. Consequently, a total of 20 reports [2–4,8,11,13–18,20–23,25–29] remained for analysis. Table 1 shows the detail of methodological quality evaluation according to CONSORT 2010 statement. The number of “Yes” varied between one and eight with a maximum possible total of nine. A total of 6 trials (30%) reported half or more items, but only one trial (5%) reported more than 80%. Meanwhile, there were nine trials (45%) reporting badly, only reporting 30% or less methodological items. The approach to estimation of sample size was reported in 9 (45%) articles [2–4,11,13,16,22,25,29]. Randomization methods were reported in four trials (20%) [22,25–27], with all generated by computers. Type of randomization was reported in three trials (15%) [25–27], all using blocking. The mechanism used to implement random allocation sequence was reported in two trials (10%), all using sequentially numbered sealed envelopes with a pre assigned random treatment [25,26]. Who enrolled participants, and who assigned participants were reported in 8 articles (40%) [2–4,11,13,25–27]. Of all the articles, seven articles [2,4,14,25–27,29] (35%) reported that all participants, including patients, care providers and result surveyors, were blinded. All 20 articles [2–4,8,11,13–18,20–23,25–29] reported baseline demographic
Fig. 1. Flow diagram showing included and excluded studies.
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Table 1 Quality evaluation of major items especially relevant to methodology according to CONSORT 2010 statement. Items 7a 8a 8b 9 10 11a 15 16 18 Number of Yes
References 2
3
4
8
11
13
14
15
16
17
18
20
21
22
23
25
26
27
28
29
Y N N N Y Y Y Y N 5 (56%)
Y N N N Y N Y N Y 4 (44%)
Y N N N Y Y Y Y Y 6 (68%)
N N N N N N Y N N 1 (11%)
Y N N N Y N Y Y Y 5 (56%)
Y N N N Y N Y N Y 4 (44%)
N N N N N Y Y N Y 3 (33%)
N N N N N N Y N N 1 (11%)
Y N N N N N Y N N 2 (22%)
N N N N N N Y N N 1 (11%)
N N N N N N Y N N 1 (11%)
N N N N N N Y N N 1 (11%)
N N N N N N Y N N 1 (11%)
Y Y N N N N Y Y N 3 (33%)
N N N N N N Y N N 1 (11%)
Y Y Y Y Y Y Y Y N 8 (89%)
N Y Y Y Y Y Y Y N 7 (78%)
N Y Y N Y Y Y Y Y 7 (78%)
N N N N N N Y N N 1 (11%)
Y N N N N Y Y Y N 4 (44%)
Number of yes 9 (45%) 4 (20%) 3 (15%) 2 (10%) 8 (40%) 7 (35%) 20 (100%) 8 (40%) 6 (30%) N/A
Y: Yes, the study mentioned the item and reported the details. N: No, the study did not mention the item.
and clinical characteristics for each group. Intention-to-treat analysis was adopted in eight articles [2,4,11,22,25–27,29] (40%). Subgroup analyses and adjusted analyses were reported in six trials [3,4,11,13,14,27] (30%), all using linear or generalized linear model. Our study provides a comprehensive assessment of the design and reporting characteristics of PubMed indexed randomized controlled trials published in IJC in 2011 based on the CONSORT Statement 2010. The CONSORT Statement was developed by an international group of clinicians, statisticians, and biomedical editors in an attempt to remedy persistent deficiencies in reporting of trial methodology [1]. Since it was first published in 1996 and revised in 2001 and 2010, the CONSORT statement has been increasingly adopted by journals, including British Medical Journal (BMJ), the Journal of the American Medical Association (JAMA), The Lancet, and the New England Journal of Medicine (NEJM), and it was recommended to reviewers and authors. The aim of sample size calculation is mainly to determinate the number of participants needed to detect a clinically relevant treatment effect. Investigators should get a large enough number of subjects in the trials to have a high power of detecting clinical significant difference between interventions. Our results suggest that only 45% conducted sample size estimation. Methods of randomization, including how to generate the random sequence, what type of randomization, how to perform allocation concealment, who assigned random sequence, are essential for internal validity so as to avoid selection bias, performance bias, detection bias and attrition bias. But in our study, only 10%–40% articles correctly reported methods of randomization. Especially for allocation concealment, only 2 articles (10%) reported correctly. It maybe related that allocation concealment mechanism (Item 9) was first added in the CONSORT Statement 2010. Blinding is an important strategy to minimize measurement bias, particularly when assessing subjective outcomes. The methods of blinding provided information about blinding of either participants or investigators after assignment to interventions which including single-blind and double-blind. In our study, only 35% articles were found correctly reported methods of blinding. The blinding method was not fully applied because some cardiology outcomes were objective, such as 6-min walking test and the exercise time on MVO2 test [2]. Correctly reported results will also avoid bias. Major items were baseline demographic characteristics, intention-to-treat analysis, subgroup or adjusted analyses. It should be equally for baseline demographic and clinical characteristics of each group, so as to exclude the impact of mixed factors. In our study, twenty articles (100%) reported baseline characteristics of each group. Intention-totreat analysis is also important for results analysis. Intention to treat analyses is done to avoid the effects of crossover and drop-out, which may break the randomization to the treatment groups in a study. Our
study found 40% articles did the intention to treat analyses. Subgroup or adjusted analyses are the statistical methods used when the baseline of each group was not equally for reducing confounding bias. In our study, only 30% articles used subgroup or adjusted analyses. We also searched Science Citation Index Expanded (SCIEXPANDED) database, and found the top cited article [25] in IJC in 2011 has 11 cited times. The article has 89% “Yes” for our methodological quality assessment. Another top ten article [14] has 33% “Yes” for the methodological quality assessment. The results suggest that improved reporting may make conclusions more credible which may increase the number of times a study is subsequently cited. In conclusion, the present study shows that the reporting of these trials does not fully follow the recommendations of CONSORT 2010. As the International Journal of Cardiology is one of the mostrecognized journals in the field of cardiology, we recommend the journal endorse the CONSORT statement, which would help researchers to improve the reporting of future randomized controlled trials. We also encourage authors to follow the CONSORT criteria when reporting the results of randomized controlled trials. Appendix A. Supplementary data Supplementary data to this article can be found online at http:// dx.doi.org/10.1016/j.ijcard.2012.06.045.
References [1] Schulz KF, Altman DG, Moher D, et al. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMJ 2010;23(340): c332. [2] Volterrani M, Cice G, Caminiti G, et al. Effect of Carvedilol, Ivabradine or their combination on exercise capacity in patients with Heart Failure (the CARVIVA HF trial). Int J Cardiol 2011;151(2):218–24. [3] Ceconi C, Freedman SB, Tardif JC, et al. Effect of heart rate reduction by ivabradine on left ventricular remodeling in the echocardiographic substudy of BEAUTIFUL. Int J Cardiol 2011;146(3):408–14. [4] Herz M, Gaspari F, Perico N, et al. Effects of high dose aleglitazar on renal function in patients with type 2 diabetes. Int J Cardiol 2011;151(2):136–42. [5] Davlouros PA, Nikokiris G, Karantalis V, et al. Neointimal coverage and stent strut apposition six months after implantation of a paclitaxel eluting stent in acute coronary syndromes: an optical coherence tomography study. Int J Cardiol 2011;151(2):155–9. [6] Andrey JL, Gomez-Soto FM, Romero SP, et al. Mortality of newly diagnosed heart failure treated with amiodarone: a propensity-matched study. Int J Cardiol 2011;151(2):175–81. [7] Al-Fiadh AH, Andrianopoulos N, Farouque O, et al. Contemporary outcomes in women undergoing percutaneous coronary intervention for acute coronary syndromes. Int J Cardiol 2011;151(2):195–9. [8] Zhang DZ, Zhu XY, Meng J, et al. Acute hemodynamic responses to adenosine and iloprost in patients with congenital heart defects and severe pulmonary arterial hypertension. Int J Cardiol 2011;147(3):433–7.
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[9] Manhenke C, Orn S, Squire I, et al. The prognostic value of circulating markers of collagen turnover after acute myocardial infarction. Int J Cardiol 2011;150(3):277–82. [10] Ather S, Peterson LE, Divakaran VG, et al. Digoxin treatment in heart failure unveiling risk by cluster analysis of DIG data. Int J Cardiol 2011;150(3):264–9. [11] Yun KH, Oh SK, Rhee SJ, et al. 12-month follow-up results of high dose rosuvastatin loading before percutaneous coronary intervention in patients with acute coronary syndrome. Int J Cardiol 2011;146(1):68–72. [12] Ekblom K, Marklund SL, Jansson JH, et al. Iron stores and HFE genotypes are not related to increased risk of first-time myocardial infarction: a prospective nested case-referent study. Int J Cardiol 2011;150(2):169–72. [13] Tenenbaum A, Shemesh J, Koren-Morag N, et al. Long-term changes in serum cholesterol level does not influence the progression of coronary calcification. Int J Cardiol 2011;150(2):130–4. [14] Erbs S, Beck EB, Linke A, et al. High-dose rosuvastatin in chronic heart failure promotes vasculogenesis, corrects endothelial function, and improves cardiac remodeling—results from a randomized, double-blind, and placebo-controlled study. Int J Cardiol 2011;146(1):56–63. [15] Rössig L, Genth-Zotz S, Rau M, et al. Argatroban for elective percutaneous coronary intervention: the ARG-E04 multi-center study. Int J Cardiol 2011;148(2):214–9. [16] Suh JW, Chung WY, Kim YS, et al. The effect of intravenous administration of erythropoietin on the infarct size in primary percutaneous coronary intervention. Int J Cardiol 2011;149(2):216–20. [17] Williams AD, Anderson MJ, Selig S, et al. Differential response to resistance training in CHF according to ACE genotype. Int J Cardiol 2011;149(3):330–4. [18] Ashton E, Windebank E, Skiba M, et al. Why did high-dose rosuvastatin not improve cardiac remodeling in chronic heart failure? Mechanistic insights from the UNIVERSE study. Int J Cardiol 2011;146(3):404–7. [19] Porto I, Dato I, Di Vito L, et al. Differential levels of circulating progenitor cells in acute coronary syndrome patients with a first event versus patients with recurring events. Int J Cardiol 2011;149(1):50–4.
[20] Njike VY, Faridi Z, Shuval K, et al. Effects of sugar-sweetened and sugar-free cocoa on endothelial function in overweight adults. Int J Cardiol 2011;149(1):83–8. [21] Tousoulis D, Koniari K, Antoniades C, et al. Combined effects of atorvastatin and metformin on glucose-induced variations of inflammatory process in patients with diabetes mellitus. Int J Cardiol 2011;149(1):46–9. [22] Schoenenberger AW, Radovanovic D, Stauffer JC, et al. Acute coronary syndromes in young patients: presentation, treatment and outcome. Int J Cardiol 2011;148(3):300–4. [23] Caminiti G, Volterrani M, Marazzi G, et al. Hydrotherapy added to endurance training versus endurance training alone in elderly patients with chronic heart failure: a randomized pilot study. Int J Cardiol 2011;148(2):199–203. [24] Ahmed MI, Lainscak M, Mujib M, et al. Gender-related dissociation in outcomes in chronic heart failure: reduced mortality but similar hospitalization in women. Int J Cardiol 2011;148(1):36–42. [25] Ferrario M, Arbustini E, Massa M, et al. High-dose erythropoietin in patients with acute myocardial infarction: a pilot, randomised, placebo-controlled study. Int J Cardiol 2011;147(1):124–31. [26] Kim HS, Lee JH, Lee SW, et al. Long-term safety and efficacy of sirolimus- vs. paclitaxel-eluting stent implantation for acute ST-elevation myocardial infarction: 3-year follow-up of the PROSIT trial. Int J Cardiol 2011;147(2):253–7. [27] Kofoed KF, Kelbæk H, Thuesen L, et al. Left ventricular contractile function after distal protection in primary percutaneous coronary intervention: results from the drug elution and distal protection in ST-elevation myocardial infarction trial. Int J Cardiol 2011;146(3):395–8. [28] Koh KK, Quon MJ, Han SH, et al. Additive beneficial effects of atorvastatin combined with amlodipine in patients with mild-to-moderate hypertension. Int J Cardiol 2011;146(3):319–25. [29] Robinson HJ, Samani NJ, Singh SJ. Can low risk cardiac patients be ‘fast tracked’ to phase IV community exercise schemes for cardiac rehabilitation? A randomised controlled trial. Int J Cardiol 2011;146(2):159–63.
0167-5273/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2012.06.045
Vasomotor function and molecular responses following drug-eluting stent in a porcine coronary model Takamitsu Nakamura a,1, Chen Jing b,1, Yin Xinhua a, Jinsheng Li a, Jack P. Chen c, Spencer B. King III a, Nicolas Chronos a, John F. McDonald d, Dongming Hou a,⁎ a
Saint Joseph's Translational Research Institute, Saint Joseph's Hospital of Atlanta, Atlanta, GA, United States Department of Cardiology, Renmin Hospital of Wuhan University, China c The Northside Heart Institute, Atlanta, GA, United States d The School of Biology, Georgia Institute of Technology, Atlanta, GA, United States b
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Article history: Received 26 March 2012 Received in revised form 30 May 2012 Accepted 8 June 2012 Available online 21 June 2012 Keywords: Drug-eluting stent Vasomotor function Gene expression
The underlying molecular mechanisms of vascular endothelial dysfunction after drug-eluting stent (DES) implantation remain undefined so far. In our previous published studies [1], profound
⁎ Corresponding author at: Saint Joseph's Translational Research Institute, 380-B Northyards Blvd., Atlanta, GA 30313, United States. E-mail address: [email protected] (D. Hou). 1 The first 2 authors contributed equally to this work.
localized inflammatory reaction, as well as enhanced local oxidative stress were seen to contribute to vasomotor dysfunction following overlapping DES. Our recent work further investigated the effects of overlap DES on coronary vasomotor function and local gene expression in porcine coronary arteries. A total of 19 animals underwent implantation of overlapping bare metal stents (BMS; n = 12), sirolimus-eluting stent (SES; n = 12), and zotaroliumseluting stents (ZES; n = 13) as previously described [2]. Each animal was randomly assigned two pairs of identical stents, implanted into any of the three epicardial coronary arteries with a 1.1:1 stent to artery ratio, as well as overlap of one-third to one-half of the stent length. One animal from the ZES group was implanted with only one pair of stents. At 28 days, endothelium-dependent vasomotor function was assessed following infusion of incremental doses of acetylcholine (Ach 10 − 6 and 10 − 5 M, 1 ml/min for 2 min). Endothelium-independent function was assessed by nitroglycerin (NTG, 200 μg). Quantitative coronary angiography was analyzed for luminal diameter changes in response to both Ach and NTG and expressed as percent of diameter change as compared with baseline. After termination, stented arteries from two animals in each group were collected for gene expression, and the remaining were used for histological evaluation.
Letters to the Editor
Reporting in randomized trials published in International Journal of Cardiology in 2011 compared to the recommendations made in CONSORT 2010 Hong-Lin Chen a, Kun Liu b,⁎ a b
Nantong University, Qi Xiu Road 19# Nantong City, Jiangsu Province, 226001, PR China Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Xi Si Road 20# Nantong City, Jiangsu Province, 226001, PR China
a r t i c l e
i n f o
Article history: Received 21 March 2012 Received in revised form 8 May 2012 Accepted 8 June 2012 Available online 25 June 2012 Keywords: Reporting quality Randomized controlled trials CONSORT statement
Since its modest beginning in 1981, the International Journal of Cardiology (IJC) has progressed to become one of the most-recognized journals in the field of cardiology. The 2010 impact factor in the Science Citation Index (SCI) is 6.802, which has risen 6-fold in the last decade. The journal aims to present all aspects of cardiovascular medicine of relevance to the clinician from genes to populations. Randomized controlled trials (RCTs) are the standard method for the evaluation of treatments and technologies in clinical medicine. It has published many RCTs in the IJC. Inadequate trial design and inadequate reporting for RCTs are associated with biased estimates of effect, and incomplete descriptions of important methodological details in RCT publications make it difficult to assess the quality of the design, conduct, and analysis of the trial and limit readers' ability to interpret the results. The Consolidated Standards of Reporting Trials (CONSORT) statement provides a standardized framework to help authors prepare reports of their trial findings in a complete and transparent manner. The aim of this study was to assess quality of reporting of trial methodology and outcomes in RCTs published in IJC based on the CONSORT Statement, and find where improvements were required for this journal. We identified studies that were classified by PubMed as randomized clinical trials and were published between January 2011 and December 2009. The specific search terms were as follows: “Journal of Cardiology” [Jour] AND Randomized Controlled Trial [ptyp] AND (“2011/1/1” [Date — Publication]: “2011/12/31” [Date — Publication]). Articles were included in the analysis if they met the following criteria: (1) the article was original article of full-length publication, not editorials, letters to the editor, reviews, case reports. or notifications of meetings and courses.; (2) the study design was a RCT, not a cohort or case -control study. The eligible trials were analyzed for the presence or absence of 9 major items relevant to methodology quality criteria from the most recent CONSORT 2010 statement. [1] These items represent the elements of study design and reporting that are most useful for the assessment of bias and validity. Quality criteria, listed with the corresponding item number from the 2010 CONSORT checklist, were as follows. (1) 7a How sample size was determined; (2) 8a method used to generate the random allocation sequence; (3) 8b type of randomization; details of any restriction (such as blocking and block size); (4) 9 allocation concealment; mechanism used to implement the random allocation sequence (such as sequentially numbered containers), describing any steps taken to conceal the sequence until interventions were assigned; (5) 10 who generated the random allocation sequence, who enrolled participants, and who assigned participants to interven⁎ Corresponding author. E-mail address: [email protected] (K. Liu).
tions; (6) 11a if done, who was blinded after assignment to interventions (for example, participants, care providers, those assessing outcomes) and how (7) 15 A table showing baseline demographic and clinical characteristics for each group; (8) 16 for each group, number of participants (denominator) included in each analysis and whether the analysis was by original assigned groups (intention-to-treat analysis); (9) 18 results of any other analyses performed, including subgroup analyses and adjusted analyses, distinguishing pre-specified from exploratory. The CONSORT 2010 statement is list in the appendix. We assigned a ‘Yes’ or ‘No’ answer to each item according to whether the author had reported it or not. Two independent reviewers evaluated the included reports. Any differences in evaluation between the reviewers were discussed and resolved. Frequencies were reported as percentages. Fig. 1 shows the process of selecting study articles. A total of 40 potentially eligible citations were identified from the initial search, of which 12 citations were excluded because those were not full-length original articles, but letters to the editor. Among the remaining 28 articles [2–29], 4 were excluded because they were cohort studies [6,7,9,12], and 4 additional non randomized controlled trials [5,10,19,24] were also excluded. Consequently, a total of 20 reports [2–4,8,11,13–18,20–23,25–29] remained for analysis. Table 1 shows the detail of methodological quality evaluation according to CONSORT 2010 statement. The number of “Yes” varied between one and eight with a maximum possible total of nine. A total of 6 trials (30%) reported half or more items, but only one trial (5%) reported more than 80%. Meanwhile, there were nine trials (45%) reporting badly, only reporting 30% or less methodological items. The approach to estimation of sample size was reported in 9 (45%) articles [2–4,11,13,16,22,25,29]. Randomization methods were reported in four trials (20%) [22,25–27], with all generated by computers. Type of randomization was reported in three trials (15%) [25–27], all using blocking. The mechanism used to implement random allocation sequence was reported in two trials (10%), all using sequentially numbered sealed envelopes with a pre assigned random treatment [25,26]. Who enrolled participants, and who assigned participants were reported in 8 articles (40%) [2–4,11,13,25–27]. Of all the articles, seven articles [2,4,14,25–27,29] (35%) reported that all participants, including patients, care providers and result surveyors, were blinded. All 20 articles [2–4,8,11,13–18,20–23,25–29] reported baseline demographic
Fig. 1. Flow diagram showing included and excluded studies.
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Table 1 Quality evaluation of major items especially relevant to methodology according to CONSORT 2010 statement. Items 7a 8a 8b 9 10 11a 15 16 18 Number of Yes
References 2
3
4
8
11
13
14
15
16
17
18
20
21
22
23
25
26
27
28
29
Y N N N Y Y Y Y N 5 (56%)
Y N N N Y N Y N Y 4 (44%)
Y N N N Y Y Y Y Y 6 (68%)
N N N N N N Y N N 1 (11%)
Y N N N Y N Y Y Y 5 (56%)
Y N N N Y N Y N Y 4 (44%)
N N N N N Y Y N Y 3 (33%)
N N N N N N Y N N 1 (11%)
Y N N N N N Y N N 2 (22%)
N N N N N N Y N N 1 (11%)
N N N N N N Y N N 1 (11%)
N N N N N N Y N N 1 (11%)
N N N N N N Y N N 1 (11%)
Y Y N N N N Y Y N 3 (33%)
N N N N N N Y N N 1 (11%)
Y Y Y Y Y Y Y Y N 8 (89%)
N Y Y Y Y Y Y Y N 7 (78%)
N Y Y N Y Y Y Y Y 7 (78%)
N N N N N N Y N N 1 (11%)
Y N N N N Y Y Y N 4 (44%)
Number of yes 9 (45%) 4 (20%) 3 (15%) 2 (10%) 8 (40%) 7 (35%) 20 (100%) 8 (40%) 6 (30%) N/A
Y: Yes, the study mentioned the item and reported the details. N: No, the study did not mention the item.
and clinical characteristics for each group. Intention-to-treat analysis was adopted in eight articles [2,4,11,22,25–27,29] (40%). Subgroup analyses and adjusted analyses were reported in six trials [3,4,11,13,14,27] (30%), all using linear or generalized linear model. Our study provides a comprehensive assessment of the design and reporting characteristics of PubMed indexed randomized controlled trials published in IJC in 2011 based on the CONSORT Statement 2010. The CONSORT Statement was developed by an international group of clinicians, statisticians, and biomedical editors in an attempt to remedy persistent deficiencies in reporting of trial methodology [1]. Since it was first published in 1996 and revised in 2001 and 2010, the CONSORT statement has been increasingly adopted by journals, including British Medical Journal (BMJ), the Journal of the American Medical Association (JAMA), The Lancet, and the New England Journal of Medicine (NEJM), and it was recommended to reviewers and authors. The aim of sample size calculation is mainly to determinate the number of participants needed to detect a clinically relevant treatment effect. Investigators should get a large enough number of subjects in the trials to have a high power of detecting clinical significant difference between interventions. Our results suggest that only 45% conducted sample size estimation. Methods of randomization, including how to generate the random sequence, what type of randomization, how to perform allocation concealment, who assigned random sequence, are essential for internal validity so as to avoid selection bias, performance bias, detection bias and attrition bias. But in our study, only 10%–40% articles correctly reported methods of randomization. Especially for allocation concealment, only 2 articles (10%) reported correctly. It maybe related that allocation concealment mechanism (Item 9) was first added in the CONSORT Statement 2010. Blinding is an important strategy to minimize measurement bias, particularly when assessing subjective outcomes. The methods of blinding provided information about blinding of either participants or investigators after assignment to interventions which including single-blind and double-blind. In our study, only 35% articles were found correctly reported methods of blinding. The blinding method was not fully applied because some cardiology outcomes were objective, such as 6-min walking test and the exercise time on MVO2 test [2]. Correctly reported results will also avoid bias. Major items were baseline demographic characteristics, intention-to-treat analysis, subgroup or adjusted analyses. It should be equally for baseline demographic and clinical characteristics of each group, so as to exclude the impact of mixed factors. In our study, twenty articles (100%) reported baseline characteristics of each group. Intention-totreat analysis is also important for results analysis. Intention to treat analyses is done to avoid the effects of crossover and drop-out, which may break the randomization to the treatment groups in a study. Our
study found 40% articles did the intention to treat analyses. Subgroup or adjusted analyses are the statistical methods used when the baseline of each group was not equally for reducing confounding bias. In our study, only 30% articles used subgroup or adjusted analyses. We also searched Science Citation Index Expanded (SCIEXPANDED) database, and found the top cited article [25] in IJC in 2011 has 11 cited times. The article has 89% “Yes” for our methodological quality assessment. Another top ten article [14] has 33% “Yes” for the methodological quality assessment. The results suggest that improved reporting may make conclusions more credible which may increase the number of times a study is subsequently cited. In conclusion, the present study shows that the reporting of these trials does not fully follow the recommendations of CONSORT 2010. As the International Journal of Cardiology is one of the mostrecognized journals in the field of cardiology, we recommend the journal endorse the CONSORT statement, which would help researchers to improve the reporting of future randomized controlled trials. We also encourage authors to follow the CONSORT criteria when reporting the results of randomized controlled trials. Appendix A. Supplementary data Supplementary data to this article can be found online at http:// dx.doi.org/10.1016/j.ijcard.2012.06.045.
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0167-5273/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2012.06.045
Vasomotor function and molecular responses following drug-eluting stent in a porcine coronary model Takamitsu Nakamura a,1, Chen Jing b,1, Yin Xinhua a, Jinsheng Li a, Jack P. Chen c, Spencer B. King III a, Nicolas Chronos a, John F. McDonald d, Dongming Hou a,⁎ a
Saint Joseph's Translational Research Institute, Saint Joseph's Hospital of Atlanta, Atlanta, GA, United States Department of Cardiology, Renmin Hospital of Wuhan University, China c The Northside Heart Institute, Atlanta, GA, United States d The School of Biology, Georgia Institute of Technology, Atlanta, GA, United States b
a r t i c l e
i n f o
Article history: Received 26 March 2012 Received in revised form 30 May 2012 Accepted 8 June 2012 Available online 21 June 2012 Keywords: Drug-eluting stent Vasomotor function Gene expression
The underlying molecular mechanisms of vascular endothelial dysfunction after drug-eluting stent (DES) implantation remain undefined so far. In our previous published studies [1], profound
⁎ Corresponding author at: Saint Joseph's Translational Research Institute, 380-B Northyards Blvd., Atlanta, GA 30313, United States. E-mail address: [email protected] (D. Hou). 1 The first 2 authors contributed equally to this work.
localized inflammatory reaction, as well as enhanced local oxidative stress were seen to contribute to vasomotor dysfunction following overlapping DES. Our recent work further investigated the effects of overlap DES on coronary vasomotor function and local gene expression in porcine coronary arteries. A total of 19 animals underwent implantation of overlapping bare metal stents (BMS; n = 12), sirolimus-eluting stent (SES; n = 12), and zotaroliumseluting stents (ZES; n = 13) as previously described [2]. Each animal was randomly assigned two pairs of identical stents, implanted into any of the three epicardial coronary arteries with a 1.1:1 stent to artery ratio, as well as overlap of one-third to one-half of the stent length. One animal from the ZES group was implanted with only one pair of stents. At 28 days, endothelium-dependent vasomotor function was assessed following infusion of incremental doses of acetylcholine (Ach 10 − 6 and 10 − 5 M, 1 ml/min for 2 min). Endothelium-independent function was assessed by nitroglycerin (NTG, 200 μg). Quantitative coronary angiography was analyzed for luminal diameter changes in response to both Ach and NTG and expressed as percent of diameter change as compared with baseline. After termination, stented arteries from two animals in each group were collected for gene expression, and the remaining were used for histological evaluation.