Cost-effectiveness of bilateral vs. single internal thoracic artery grafts at 10 years.

AIMS: Using bilateral internal thoracic arteries (BITAs) for coronary artery bypass grafting (CABG) has been suggested to improve survival compared to CABG using single internal thoracic arteries (SITAs) for patients with advanced coronary artery disease. We used data from the Arterial Revascularization Trial (ART) to assess long-term cost-effectiveness of BITA grafting compared to SITA grafting from an English health system perspective. METHODS AND RESULTS: Resource use, healthcare costs, and quality-adjusted life years (QALYs) were assessed across 10 years of follow-up from an intention-to-treat perspective. Missing data were addressed using multiple imputation. Incremental cost-effectiveness ratios were calculated with uncertainty characterized using non-parametric bootstrapping. Results were extrapolated beyond 10 years using Gompertz functions for survival and linear models for total cost and utility. Total mean costs at 10 years of follow-up were £17 594 in the BITA arm and £16 462 in the SITA arm [mean difference £1133 95% confidence interval (CI) £239 to £2026, P = 0.015]. Total mean QALYs at 10 years were 6.54 in the BITA arm and 6.57 in the SITA arm (adjusted mean difference -0.01 95% CI -0.2 to 0.1, P = 0.883). At 10 years, BITA grafting had a 33% probability of being cost-effective compared to SITA, assuming a cost-effectiveness threshold of £20 000. Lifetime extrapolation increased the probability of BITA being cost-effective to 51%. CONCLUSIONS: BITA grafting has significantly higher costs but similar quality-adjusted survival at 10 years compared to SITA grafting. Extrapolation suggests this could change over lifetime.

Bilateral versus Single Internal-Thoracic-Artery Grafts at 10 Years.

BACKGROUND: Multiple arterial grafts may result in longer survival than single arterial grafts after coronary-artery bypass grafting (CABG) surgery. We evaluated the use of bilateral internal-thoracic-artery grafts for CABG. METHODS: We randomly assigned patients scheduled for CABG to undergo bilateral or single internal-thoracic-artery grafting. Additional arterial or vein grafts were used as indicated. The primary outcome was death from any cause at 10 years. The composite of death from any cause, myocardial infarction, or stroke was a secondary outcome. RESULTS: A total of 1548 patients were randomly assigned to undergo bilateral internal-thoracic-artery grafting (the bilateral-graft group) and 1554 to undergo single internal-thoracic-artery grafting (the single-graft group). In the bilateral-graft group, 13.9% of the patients received only a single internal-thoracic-artery graft, and in the single-graft group, 21.8% of the patients also received a radial-artery graft. Vital status was not known for 2.3% of the patients at 10 years. In the intention-to-treat analysis at 10 years, there were 315 deaths (20.3% of the patients) in the bilateral-graft group and 329 deaths (21.2%) in the single-graft group (hazard ratio, 0.96; 95% confidence interval [CI], 0.82 to 1.12; P=0.62). Regarding the composite outcome of death, myocardial infarction, or stroke, there were 385 patients (24.9%) with an event in the bilateral-graft group and 425 patients (27.3%) with an event in the single-graft group (hazard ratio, 0.90; 95% CI, 0.79 to 1.03). CONCLUSIONS: Among patients who were scheduled for CABG and had been randomly assigned to undergo bilateral or single internal-thoracic-artery grafting, there was no significant between-group difference in the rate of death from any cause at 10 years in the intention-to-treat analysis. Further studies are needed to determine whether multiple arterial grafts provide better outcomes than a single internal-thoracic-artery graft. (Funded by the British Heath Foundation and others; Current Controlled Trials number, ISRCTN46552265 .).

Overinterpretation and misreporting of prognostic factor studies in oncology: a systematic review.

BACKGROUND: Cancer prognostic biomarkers have shown disappointing clinical applicability. The objective of this study was to classify and estimate how study results are overinterpreted and misreported in prognostic factor studies in oncology. METHODS: This systematic review focused on 17 oncology journals with an impact factor above 7. PubMed was searched for primary clinical studies published in 2015, evaluating prognostic factors. We developed a classification system, focusing on three domains: misleading reporting (selective, incomplete reporting, misreporting), misleading interpretation (unreliable statistical analysis, spin) and misleading extrapolation of the results (claiming irrelevant clinical applicability, ignoring uncertainty). RESULTS: Our search identified 10,844 articles. The 98 studies included investigated a median of two prognostic factors (Q1-Q3, 1-7). The prognostic factors' effects were selectively and incompletely reported in 35/98 and 24/98 full texts, respectively. Twenty-nine articles used linguistic spin in the form of strong statements. Linguistic spin rejecting non-significant results was found in 34 full-text results and 15 abstract results sections. One in five articles had discussion and/or abstract conclusions that were inconsistent with the study findings. Sixteen reports had discrepancies between their full-text and abstract conclusions. CONCLUSIONS: Our study provides evidence of frequent overinterpretation of findings of prognostic factor assessment in high-impact medical oncology journals.

Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK): An Abridged Explanation and Elaboration.

The Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK) were developed to address widespread deficiencies in the reporting of such studies. The REMARK checklist consists of 20 items to report for published tumor marker prognostic studies. A detailed paper was published explaining the rationale behind checklist items, providing positive examples and giving empirical evidence of the quality of reporting. REMARK provides a comprehensive overview to educate on good reporting and provide a valuable reference for the many issues to consider when designing, conducting, and analyzing tumor marker studies and prognostic studies in medicine in general. Despite support for REMARK from major cancer journals, prognostic factor research studies remain poorly reported. To encourage dissemination and uptake of REMARK, we have produced this considerably abridged version of the detailed explanatory manuscript, which may also serve as a brief guide to key issues for investigators planning tumor marker prognostic studies. To summarize the current situation, more recent papers investigating the quality of reporting and related reporting guidelines are cited, but otherwise the literature is not updated. Another important impetus for this paper is that it serves as a basis for literal translations into other languages. Translations will help to bring key information to a larger audience world-wide. Many more details can be found in the original paper.

Safety of Perioperative Aprotinin Administration During Isolated Coronary Artery Bypass Graft Surgery: Insights From the ART (Arterial Revascularization Trial).

BACKGROUND: There is still uncertainty about the safety of aprotinin for coronary artery bypass graft surgery. The ART (Arterial Revascularization Trial) was designed to compare survival after bilateral versus single internal thoracic artery grafting. Many of the ART patients (≈30%) received perioperative aprotinin. We investigated the association between perioperative aprotinin administration and short-term (in-hospital) and long-term outcomes by performing a post hoc analysis of the ART. METHODS AND RESULTS: Among patients enrolled in the ART (n=3102) from 2004 to 2007, we excluded those who did not undergo surgery (n=18) and those with no information about use of perioperative aprotinin (n=9). Finally, 836 of 3076 patients (27%) received aprotinin. Propensity matching was used to select 536 pairs for final comparison. Aprotinin was also associated with an increased risk of hospital mortality (9 [1.7%] versus 1 [0.2%]; odds ratio, 9.12; 95% confidence interval [CI], 1.15-72.2; P=0.03), intra-aortic balloon pump insertion (37 [6.9%] versus 17 [3.2%]; odds ratio, 2.26; 95% CI, 1.26-4.07; P=0.006), and acute kidney injury (102 [19.0%] versus 76 [14.2%]; odds ratio, 1.42; 95% CI, 1.03-1.97; P=0.03). Aprotinin was not associated with a lower incidence of transfusion (37 [6.9%] versus 28 [5.2%]; odds ratio, 1.34; 95% CI, 0.81-2.23; P=0.25) and reexploration (26 [4.9%] versus 19 [3.5%]; hazard ratio, 1.39; 95% CI, 0.76-2.53; P=0.28). At 5 years, all-cause mortality was significantly increased in the aprotinin group (56 [10.6%] versus 38 [7.3%]; hazard ratio, 1.51; 95% CI, 1.0-2.28; P=0.045). CONCLUSIONS: In the present post hoc ART analysis, aprotinin was associated with a significantly increased risk of early and late mortality. CLINICAL TRIAL REGISTRATION: URL: http://www.isrctn.com. Unique identifier: ISRCTN46552265.

Incidence and clinical implications of intraoperative bilateral internal thoracic artery graft conversion: Insights from the Arterial Revascularization Trial.

BACKGROUND: The Arterial Revascularization Trial has been designed to answer the question whether the use of bilateral internal thoracic arteries can improve 10-year outcomes when compared with single internal thoracic arteries. In the Arterial Revascularization Trial, a significant proportion of patients initially allocated to bilateral internal thoracic arteries received other conduit strategies. We sought to investigate the incidence and clinical implication of bilateral internal thoracic artery graft conversion in the Arterial Revascularization Trial. METHODS: Among patients enrolled in the Arterial Revascularization Trial (n = 3102), we excluded those allocated to single internal thoracic arteries (n = 1554), those who did not undergo surgery (n = 16), and those who underwent operation but withdrew after randomization (n = 7). Propensity score matching was used to compare converted versus nonconverted bilateral internal thoracic artery groups. RESULTS: A total of 1525 patients were operated with the intention to receive bilateral internal thoracic artery grafting. Of those, 233 (15.3%) were converted to other conduit selection strategies. Incidence of conversion largely varied across 131 participating surgeons (from 0% to 100%). The most common reason for bilateral internal thoracic artery graft conversion was the evidence of at least 1 internal thoracic artery that was not suitable, which was reported in 77 cases. Patients with intraoperative bilateral internal thoracic artery graft conversion received a lower number of grafts (2.95 ± 0.84 vs 3.21 ± 0.74; P < .001). However, the hospital mortality rate was comparable to that of those who did not require bilateral internal thoracic artery graft conversion (0% vs 1.6%; P = .1), as well as the incidence of major complications. At 5 years, we found a nonsignificant excess of deaths (11.9% vs 8.4%; P = .1) and major adverse events (17.1% 13.2%; P = .1) mainly driven by an excess of revascularization in patients requiring conversion. CONCLUSIONS: The incidence of intraoperative bilateral internal thoracic artery graft conversion is not infrequent. Bilateral internal thoracic artery graft conversion is not associated with increased operative morbidity, but its effect on late outcomes remains uncertain.

Reporting guidelines for oncology research: helping to maximise the impact of your research.

Many reports of health research omit important information needed to assess their methodological robustness and clinical relevance. Without clear and complete reporting, it is not possible to identify flaws or biases, reproduce successful interventions, or use the findings in systematic reviews or meta-analyses. The EQUATOR Network (http://www.equator-network.org/) promotes responsible reporting and the use of reporting guidelines to improve the accuracy, completeness, and transparency of health research. EQUATOR supports researchers by providing online resources and training. EQUATOR Oncology, a project funded by Cancer Research UK, aims to support cancer researchers reporting their research through the provision of online resources. In this article, our objective is to highlight reporting issues related to oncology research publications and to introduce reporting guidelines that are designed to aid high-quality reporting. We describe generic reporting guidelines for the main study types, and explain how these guidelines should and should not be used. We also describe 37 oncology-specific reporting guidelines, covering different clinical areas (e.g., haematology or urology) and sections of the report (e.g., methods or study characteristics); most of these are little-used. We also provide some background information on EQUATOR Oncology, which focuses on addressing the reporting needs of the oncology research community.

Germline BRCA mutation and outcome in young-onset breast cancer (POSH): a prospective cohort study.

BACKGROUND: Retrospective studies provide conflicting interpretations of the effect of inherited genetic factors on the prognosis of patients with breast cancer. The primary aim of this study was to determine the effect of a germline BRCA1 or BRCA2 mutation on breast cancer outcomes in patients with young-onset breast cancer. METHODS: We did a prospective cohort study of female patients recruited from 127 hospitals in the UK aged 40 years or younger at first diagnosis (by histological confirmation) of invasive breast cancer. Patients with a previous invasive malignancy (except non-melanomatous skin cancer) were excluded. Patients were identified within 12 months of initial diagnosis. BRCA1 and BRCA2 mutations were identified using blood DNA collected at recruitment. Clinicopathological data, and data regarding treatment and long-term outcomes, including date and site of disease recurrence, were collected from routine medical records at 6 months, 12 months, and then annually until death or loss to follow-up. The primary outcome was overall survival for all BRCA1 or BRCA2 mutation carriers (BRCA-positive) versus all non-carriers (BRCA-negative) at 2 years, 5 years, and 10 years after diagnosis. A prespecified subgroup analysis of overall survival was done in patients with triple-negative breast cancer. Recruitment was completed in 2008, and long-term follow-up is continuing. FINDINGS: Between Jan 24, 2000, and Jan 24, 2008, we recruited 2733 women. Genotyping detected a pathogenic BRCA mutation in 338 (12%) patients (201 with BRCA1, 137 with BRCA2). After a median follow-up of 8·2 years (IQR 6·0-9·9), 651 (96%) of 678 deaths were due to breast cancer. There was no significant difference in overall survival between BRCA-positive and BRCA-negative patients in multivariable analyses at any timepoint (at 2 years: 97·0% [95% CI 94·5-98·4] vs 96·6% [95·8-97·3]; at 5 years: 83·8% [79·3-87·5] vs 85·0% [83·5-86·4]; at 10 years: 73·4% [67·4-78·5] vs 70·1% [67·7-72·3]; hazard ratio [HR] 0·96 [95% CI 0·76-1·22]; p=0·76). Of 558 patients with triple-negative breast cancer, BRCA mutation carriers had better overall survival than non-carriers at 2 years (95% [95% CI 89-97] vs 91% [88-94]; HR 0·59 [95% CI 0·35-0·99]; p=0·047) but not 5 years (81% [73-87] vs 74% [70-78]; HR 1·13 [0·70-1·84]; p=0·62) or 10 years (72% [62-80] vs 69% [63-74]; HR 2·12 [0·82-5·49]; p= 0·12). INTERPRETATION: Patients with young-onset breast cancer who carry a BRCA mutation have similar survival as non-carriers. However, BRCA mutation carriers with triple-negative breast cancer might have a survival advantage during the first few years after diagnosis compared with non-carriers. Decisions about timing of additional surgery aimed at reducing future second primary-cancer risks should take into account patient prognosis associated with the first malignancy and patient preferences. FUNDING: Cancer Research UK, the UK National Cancer Research Network, the Wessex Cancer Trust, Breast Cancer Now, and the PPP Healthcare Medical Trust Grant.

Off-pump versus on-pump coronary artery bypass grafting: Insights from the Arterial Revascularization Trial.

BACKGROUND: The long-term effects of off-pump coronary artery bypass continue to be controversial because some studies have reported increased adverse event rates with off-pump coronary artery bypass when compared with on-pump coronary artery bypass. The Arterial Revascularization Trial compared survival after bilateral versus single internal thoracic artery grafting. The choice of off-pump coronary artery bypass versus on-pump coronary artery bypass was based on the surgeon's discretion. We performed a post hoc analysis of the Arterial Revascularization Trial to compare 5-year outcomes with 2 strategies. METHODS: Among 3102 patients enrolled in the Arterial Revascularization Trial, we selected 1260 patients who underwent off-pump coronary artery bypass versus 1700 patients who underwent on-pump coronary artery bypass with cardioplegic arrest for the present comparison. Primary outcomes were 5-year mortality and incidence of major cardiac and cerebrovascular events, including cardiovascular death, myocardial infarction, cerebrovascular accident, and revascularization after index procedure. Propensity score matching selected 1260 pairs for final comparison. Stratified Cox models were used for treatment effect estimate. RESULTS: Hospital mortality was comparable between off-pump coronary artery bypass and on-pump coronary artery bypass groups (12 [1.0%] vs 15 [1.2%]; P = .7). Conversion rate to on-pump during off-pump coronary artery bypass was 29 of 1260 (2.3%). When compared with off-pump coronary artery bypass not converted, off-pump coronary artery bypass converted to on-pump presented a remarkably higher hospital mortality (10.3% vs 0.7%; P < .001). At 5 years, the mortality rate was 110 (8.9%) versus 102 (8.3%) in the off-pump coronary artery bypass and on-pump coronary artery bypass groups, respectively, with no significant difference (hazard ratio, 1.14; 95% confidence interval, 0.86-1.52; P = .35). Incidence of major cardiac and cerebrovascular events was 175 (14.3) versus 169 (13.8) in the off-pump coronary artery bypass and on-pump coronary artery bypass groups, respectively, with no significant difference (hazard ratio, 1.05; 95% confidence interval, 0.84-1.31; P = .65). CONCLUSIONS: The present post hoc Arterial Revascularization Trial analysis supports the hypothesis that both off-pump coronary artery bypass and on-pump coronary artery bypass are equally effective and safe.

Support for reporting guidelines in surgical journals needs improvement: A systematic review.

INTRODUCTION: Evidence-based medicine works best if the evidence is reported well. Past studies have shown reporting quality to be lacking in the field of surgery. Reporting guidelines are an important tool for authors to optimize the reporting of their research. The objective of this study was to analyse the frequency and strength of recommendation for such reporting guidelines within surgical journals. METHODS: A systematic review of the 198 journals within the Journal Citation Report 2014 (surgery category) published by Thomson Reuters was undertaken. The online guide for authors for each journal was screened by two independent groups and results compared. Data regarding the presence and strength of recommendation to use reporting guidelines was extracted. RESULTS: 193 journals were included (as five appeared twice having changed their name). These had a median impact factor of 1.526 (range 0.047-8.327), with a median of 145 articles published per journal (range 29-659), with 34,036 articles published in total over the two-year window 2012-2013. The majority (62%) of surgical journals made no mention of reporting guidelines within their guidelines for authors. Of the 73 (38%) that did mention them, only 14% (10/73) required the use of all relevant reporting guidelines. The most frequently mentioned reporting guideline was CONSORT (46 journals). CONCLUSIONS: The mention of reporting guidelines within the guide for authors of surgical journals needs improvement. Authors, reviewers and editors should work to ensure that research is reported in line with the relevant reporting guidelines. Journals should consider hard-wiring adherence to them.

Associations Between Adding a Radial Artery Graft to Single and Bilateral Internal Thoracic Artery Grafts and Outcomes: Insights From the Arterial Revascularization Trial.

BACKGROUND: Whether the use of the radial artery (RA) can improve clinical outcomes in coronary artery bypass graft surgery remains unclear. The ART (Arterial Revascularization Trial) was designed to compare survival after bilateral internal thoracic artery (BITA) over single left internal thoracic artery (SITA). In the ART, a large proportion of patients (≈20%) also received an RA graft instead of a saphenous vein graft (SVG). We aimed to investigate the associations between using the RA instead of an SVG to supplement SITA or BITA grafts and outcomes by performing a post hoc analysis of the ART. METHODS: Patients enrolled in the ART (n=3102) were classified on the basis of conduits actually received (as treated). The analysis included 2737 patients who received an RA graft (RA group; n=632) or SVG only (SVG group; n=2105) in addition to SITA or BITA grafts. The primary end point was the composite of myocardial infarction, cardiovascular death, and repeat revascularization at 5 years. Propensity score matching and stratified Cox regression were used to compare the 2 strategies. RESULTS: Myocardial infarction, cardiovascular death, and repeat revascularization cumulative incidence was 2.3% (95% confidence interval [CI], 1.1-3.4), 3.5% (95% CI, 2.1-5.0), and 4.4% (95% CI, 2.8-6.0) in the RA group and 3.4% (95% CI, 2.0-4.8), 4.0% (95% CI, 2.5-5.6), and 7.6% (95% CI, 5.5-9.7) in the SVG group, respectively. The composite end point was significantly lower in the RA group (8.8%; 95% CI, 6.5-11.0) compared with the SVG group (13.6%; 95% CI, 10.8-16.3; P=0.005). This association was present when an RA graft was used to supplement both SITA and BITA grafts (interaction P=0.62). CONCLUSIONS: This post hoc ART analysis showed that an additional RA was associated with lower risk for midterm major adverse cardiac events when used to supplement SITA or BITA grafts. CLINICAL TRIAL REGISTRATION: URL: https://www.situ.ox.ac.uk/surgical-trials/art. Unique identifier: ISRCTN46552265.

CONSORT Statement for Randomized Trials of Nonpharmacologic Treatments: A 2017 Update and a CONSORT Extension for Nonpharmacologic Trial Abstracts.

Incomplete and inadequate reporting is an avoidable waste that reduces the usefulness of research. The CONSORT (Consolidated Standards of Reporting Trials) Statement is an evidence-based reporting guideline that aims to improve research transparency and reduce waste. In 2008, the CONSORT Group developed an extension to the original statement that addressed methodological issues specific to trials of nonpharmacologic treatments (NPTs), such as surgery, rehabilitation, or psychotherapy. This article describes an update of that extension and presents an extension for reporting abstracts of NPT trials. To develop these materials, the authors reviewed pertinent literature published up to July 2016; surveyed authors of NPT trials; and conducted a consensus meeting with editors, trialists, and methodologists. Changes to the CONSORT Statement extension for NPT trials include wording modifications to improve readers' understanding and the addition of 3 new items. These items address whether and how adherence of participants to interventions is assessed or enhanced, description of attempts to limit bias if blinding is not possible, and specification of the delay between randomization and initiation of the intervention. The CONSORT extension for abstracts of NPT trials includes 2 new items that were not specified in the original CONSORT Statement for abstracts. The first addresses reporting of eligibility criteria for centers where the intervention is performed and for care providers. The second addresses reporting of important changes to the intervention versus what was planned. Both the updated CONSORT extension for NPT trials and the CONSORT extension for NPT trial abstracts should help authors, editors, and peer reviewers improve the transparency of NPT trial reports.

Did the reporting of prognostic studies of tumour markers improve since the introduction of REMARK guideline? A comparison of reporting in published articles.

Although biomarkers are perceived as highly relevant for future clinical practice, few biomarkers reach clinical utility for several reasons. Among them, poor reporting of studies is one of the major problems. To aid improvement, reporting guidelines like REMARK for tumour marker prognostic (TMP) studies were introduced several years ago. The aims of this project were to assess whether reporting quality of TMP-studies improved in comparison to a previously conducted study assessing reporting quality of TMP-studies (PRE-study) and to assess whether articles citing REMARK (citing group) are better reported, in comparison to articles not citing REMARK (not-citing group). For the POST-study, recent articles citing and not citing REMARK (53 each) were identified in selected journals through systematic literature search and evaluated in same way as in the PRE-study. Ten of the 20 items of the REMARK checklist were evaluated and used to define an overall score of reporting quality. The observed overall scores were 53.4% (range: 10%-90%) for the PRE-study, 57.7% (range: 20%-100%) for the not-citing group and 58.1% (range: 30%-100%) for the citing group of the POST-study. While there is no difference between the two groups of the POST-study, the POST-study shows a slight but not relevant improvement in reporting relative to the PRE-study. Not all the articles of the citing group, cited REMARK appropriately. Irrespective of whether REMARK was cited, the overall score was slightly higher for articles published in journals requesting adherence to REMARK than for those published in journals not requesting it: 59.9% versus 51.9%, respectively. Several years after the introduction of REMARK, many key items of TMP-studies are still very poorly reported. A combined effort is needed from authors, editors, reviewers and methodologists to improve the current situation. Good reporting is not just nice to have but is essential for any research to be useful.

One-year costs of bilateral or single internal mammary grafts in the Arterial Revascularisation Trial.

OBJECTIVE: Coronary artery bypass grafting (CABG) using bilateral internal mammary arteries (BIMA) may improve survival over CABG using single internal mammary arteries (SIMA), but may be surgically more complex (and therefore costly) and associated with impaired sternal wound healing. We report, for the first time, a detailed comparison of healthcare resource use and costs over 12 months, as part of the Arterial Revascularisation (ART) Trial. METHODS: 3102 patients in 28 hospitals in seven countries were randomised to CABG surgery using BIMA (n=1548) or SIMA (n=1554). Detailed resource use data were collected covering surgery, the initial hospital episode, and for 12 months post randomisation. Using UK unit costs, total costs were calculated and compared between trial arms and for subgroups. RESULTS: Patients randomised to BIMA spent 20 min longer in theatre (95% CI 15 to 25, p<0.001) and also required more treatment for sternal wound problems. Mean (SD) total costs per patient at 12 months were £13 839 (£10 534) for BIMA and £12 717 (£9719) for SIMA (mean cost difference £1122, 95% CI £407 to £1838, p=0.002). No tests for interaction between subgroups and treatment allocation were significant. CONCLUSIONS: At 12 months from randomisation, mean costs were approximately 9% higher in BIMA than SIMA patients, primarily due to longer time in theatre and in-hospital stay, and slightly higher costs related to sternal wound problems during follow-up. Follow-up to the primary trial endpoint of 10 years will reveal whether longer-term differences emerge in graft patency or in overall survival. TRIAL REGISTRATION NUMBER: Controlled-trials.com (ISRCTN46552265).

Impact of dual antiplatelet therapy after coronary artery bypass surgery on 1-year outcomes in the Arterial Revascularization Trial.

OBJECTIVES: There is still little evidence to boldport routine dual antiplatelet therapy (DAPT) with P2Y12 antagonists following coronary artery bypass grafting (CABG). The Arterial Revascularization Trial (ART) was designed to compare 10-year survival after bilateral versus single internal thoracic artery grafting. We aimed to get insights into the effect of DAPT (with clopidogrel) following CABG on 1-year outcomes by performing a post hoc ART analysis. METHODS: Among patients enrolled in the ART (n = 3102), 609 (21%) and 2308 (79%) were discharged on DAPT or aspirin alone, respectively. The primary end-point was the incidence of major adverse cerebrovascular and cardiac events (MACCE) at 1 year including cardiac death, myocardial infarction, cerebrovascular accident and reintervention; safety end-point was bleeding requiring hospitalization. Propensity score (PS) matching was used to create comparable groups. RESULTS: Among 609 PS-matched pairs, MACCE occurred in 34 (5.6%) and 34 (5.6%) in the DAPT and aspirin alone groups, respectively, with no significant difference between the 2 groups [hazard ratio (HR) 0.97, 95% confidence interval (CI) 0.59-1.59; P = 0.90]. Only 188 (31%) subjects completed 1 year of DAPT, and in this subgroup, MACCE rate was 5.8% (HR 1.11, 95% CI 0.53-2.30; P = 0.78). In the overall sample, bleeding rate was higher in DAPT group (2.3% vs 1.1%; P = 0.02), although this difference was no longer significant after matching (2.3% vs 1.8%; P = 0.54). CONCLUSIONS: Based on these findings, when compared with aspirin alone, DAPT with clopidogrel prescribed at discharge was not associated with a significant reduction of adverse cardiac and cerebrovascular events at 1 year following CABG.

Randomized Trial of Bilateral versus Single Internal-Thoracic-Artery Grafts.

BACKGROUND: The use of bilateral internal thoracic (mammary) arteries for coronary-artery bypass grafting (CABG) may improve long-term outcomes as compared with the use of a single internal-thoracic-artery plus vein grafts. METHODS: We randomly assigned patients scheduled for CABG to undergo single or bilateral internal-thoracic-artery grafting in 28 cardiac surgical centers in seven countries. The primary outcome was death from any cause at 10 years. The composite of death from any cause, myocardial infarction, or stroke was a secondary outcome. Interim analyses were prespecified at 5 years of follow-up. RESULTS: A total of 3102 patients were enrolled; 1554 were randomly assigned to undergo single internal-thoracic-artery grafting (the single-graft group) and 1548 to undergo bilateral internal-thoracic-artery grafting (the bilateral-graft group). At 5 years of follow-up, the rate of death was 8.7% in the bilateral-graft group and 8.4% in the single-graft group (hazard ratio, 1.04; 95% confidence interval [CI], 0.81 to 1.32; P=0.77), and the rate of the composite of death from any cause, myocardial infarction, or stroke was 12.2% and 12.7%, respectively (hazard ratio, 0.96; 95% CI, 0.79 to 1.17; P=0.69). The rate of sternal wound complication was 3.5% in the bilateral-graft group versus 1.9% in the single-graft group (P=0.005), and the rate of sternal reconstruction was 1.9% versus 0.6% (P=0.002). CONCLUSIONS: Among patients undergoing CABG, there was no significant difference between those receiving single internal-thoracic-artery grafts and those receiving bilateral internal-thoracic-artery grafts with regard to mortality or the rates of cardiovascular events at 5 years of follow-up. There were more sternal wound complications with bilateral internal-thoracic-artery grafting than with single internal-thoracic-artery grafting. Ten-year follow-up is ongoing. (Funded by the British Heart Foundation and others; ART Current Controlled Trials number, ISRCTN46552265 .).

Pedicled and skeletonized single and bilateral internal thoracic artery grafts and the incidence of sternal wound complications: Insights from the Arterial Revascularization Trial.

OBJECTIVES: The question of whether skeletonized internal thoracic artery harvesting reduces the incidence of sternal wound complications in comparison with the pedicled technique, in the context of single or bilateral internal thoracic arteries, remains controversial. We studied the impact of the internal thoracic artery harvesting strategy on sternal wound complication in the Arterial Revascularization Trial. METHODS: Patients enrolled in the Arterial Revascularization Trial (n = 3102) were randomized to coronary artery bypass grafting with single or bilateral internal thoracic arteries. Sternal wound complication rates were examined according to the harvesting technique that was documented in 2056 patients. The internal thoracic artery harvesting technique, based on the surgeon's preference, resulted in 4 groups: pedicled single internal thoracic artery (n = 607), pedicled bilateral internal thoracic artery (n = 459), skeletonized single internal thoracic artery (n = 512), and skeletonized bilateral internal thoracic artery (n = 478). Propensity scores weighting was used to estimate the impact of the harvesting technique on sternal wound complications. RESULTS: A total of 219 of 2056 patients (10.6%) experienced a sternal wound complication within 1 year from the index operation. Of those, only 25 patients (1.2%) required sternal wound reconstruction. Pedicled bilateral internal thoracic artery (odds ratio [OR], 1.80; 95% confidence interval [CI], 1.23-2.63) but not skeletonized bilateral internal thoracic artery (OR, 1.00; 95% CI, 0.65-1.53) or skeletonized single internal thoracic artery (OR, 0.89; 95% CI, 0.57-1.38) was associated with a significantly increased risk of any sternal wound complications compared with pedicled single internal thoracic artery. CONCLUSIONS: The present Arterial Revascularization Trial substudy suggests that, with a skeletonization technique, the risk of sternal wound complication with bilateral internal thoracic artery grafting is similar to that after standard pedicled single internal thoracic artery harvesting, whereas skeletonized single internal thoracic artery harvesting did not add any further benefit when compared with pedicled single internal thoracic artery harvesting.

Declaración SPIRIT 2013: definición de los elementos estándares del protocolo de un ensayo clínico / SPIRIT 2013 Statement: defining standard protocol items for clinical trials

El protocolo de un ensayo clínico es la base para planificar, ejecutar, publicar y evaluar el ensayo. Sin embargo, los protocolos y las guías que existen para su elaboración varían enormemente en cuanto a su calidad y contenido. En este artículo se describe la elaboración sistemática y el alcance de la Declaración SPIRIT 2013 (denominada así por la sigla en inglés de Standard Protocol items: Recommendations for Interventional Trials o Elementos estándares de un protocolo: recomendaciones para los ensayos de intervención), una guía en la que se establecen los contenidos mínimos que debe tener el protocolo de un ensayo clínico. La lista de comprobación de la declaración SPIRIT, que consta de 33 elementos, se aplica a los protocolos de todos los ensayos clínicos y se centra más en el contenido que en el formato. En esta lista se recomienda hacer una descripción completa de lo que se ha planificado, aunque no se establece cómo diseñar o ejecutar un ensayo. Al brindar orientación sobre los contenidos fundamentales, las recomendaciones SPIRIT procuran facilitar la redacción de protocolos de alta calidad. El cumplimiento de las recomendaciones SPIRIT debería mejorar la transparencia y la exhaustividad de los protocolos de los ensayos en beneficio de los investigadores, los participantes, los pacientes, los patrocinadores, los financiadores, los comités de ética de la investigación o las juntas de revisión institucionales, los revisores, las revistas biomédicas, los registros de ensayos, los formuladores de políticas, los organismos reguladores y otras partes interesadas clave.

The protocol of a clinical trial serves as the foundation for study planning, conduct, reporting, and appraisal. However, trial protocols and existing protocol guidelines vary greatly in content and quality. This article describes the systematic development and scope of SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013, a guideline for the minimum content of a clinical trial protocol. The 33-item SPIRIT checklist applies to protocols for all clinical trials and focuses on content rather than format. The checklist recommends a full description of what is planned; it does not prescribe how to design or conduct a trial. By providing guidance for key content, the SPIRIT recommendations aim to facilitate the drafting of high-quality protocols. Adherence to SPIRIT would also enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, sponsors, funders, research ethics committees or institutional review boards, peer reviewers, journals, trial registries, policymakers, regulators, and other key stakeholders.

A systematic review protocol for reporting deficiencies within surgical case series.

INTRODUCTION: Case series are an important and common study type in surgical literature. There is evidence that key data are excluded from published case series, and currently no reporting guideline exists for case series. There is, therefore, the potential to change practices and improve the reporting of case series. Reporting guidelines have been shown to be efficacious in raising the bar for reporting quality. We present our protocol for the first stage of guideline development--a systematic review of previously identified deficiencies in how surgical case series are reported. METHODS AND ANALYSIS: Electronic searches will be conducted on MEDLINE, EMBASE, Cochrane Methods Register, Science Citation Index and Conference Proceedings Citation Index, from the start of indexing until 5 November 2014. The electronic search strategy was developed with an information specialist. Two independent researchers will identify articles for inclusion, specifically those that describe reporting deficiencies within surgical case series. Data will be extracted to specifically focus on the deficiencies of reporting. These will be categorised according to their type, and other identified issues will also be presented. Data will be presented with descriptive statistics to determine frequently missing types of data, and the commonest reporting issues tabulated. ETHICS AND DISSEMINATION: The authors hope to disseminate the findings as widely as possible, irrespective of results, as these will add to the wider corpora of information on this subject. The systematic review will be published in a peer-reviewed journal and will be presented at a wide range of national and international conferences. Ultimately, this will inform a Delphi process for the development of a surgical case series reporting guideline. PROTOCOL REGISTRATION: CRD42015016145.

Assessment of the Incremental Benefit of Computer-Aided Detection (CAD) for Interpretation of CT Colonography by Experienced and Inexperienced Readers.

OBJECTIVES: To quantify the incremental benefit of computer-assisted-detection (CAD) for polyps, for inexperienced readers versus experienced readers of CT colonography. METHODS: 10 inexperienced and 16 experienced radiologists interpreted 102 colonography studies unassisted and with CAD utilised in a concurrent paradigm. They indicated any polyps detected on a study sheet. Readers' interpretations were compared against a ground-truth reference standard: 46 studies were normal and 56 had at least one polyp (132 polyps in total). The primary study outcome was the difference in CAD net benefit (a combination of change in sensitivity and change in specificity with CAD, weighted towards sensitivity) for detection of patients with polyps. RESULTS: Inexperienced readers' per-patient sensitivity rose from 39.1% to 53.2% with CAD and specificity fell from 94.1% to 88.0%, both statistically significant. Experienced readers' sensitivity rose from 57.5% to 62.1% and specificity fell from 91.0% to 88.3%, both non-significant. Net benefit with CAD assistance was significant for inexperienced readers but not for experienced readers: 11.2% (95%CI 3.1% to 18.9%) versus 3.2% (95%CI -1.9% to 8.3%) respectively. CONCLUSIONS: Concurrent CAD resulted in a significant net benefit when used by inexperienced readers to identify patients with polyps by CT colonography. The net benefit was nearly four times the magnitude of that observed for experienced readers. Experienced readers did not benefit significantly from concurrent CAD.