Abstract Objective To compare methodological characteristics of randomized controlled trials (RCTs) published in higher vs. lower impact Core Clinical Journals. Study Design and Setting We searched ...MEDLINE for RCTs published in 2007 in Core Clinical Journals. We randomly sampled 1,140 study reports in a 1:1 ratio in higher (five general medicine journals with the highest total citations in 2007) and lower impact journals. Results Four hundred sixty-nine RCTs proved eligible: 219 in higher and 250 in lower impact journals. RCTs in higher vs. lower impact journals had larger sample sizes (median, 285 vs. 39), were more likely to receive industry funding (53% vs. 28%), declare concealment of allocation (66% vs. 36%), declare blinding of health care providers (53% vs. 41%) and outcome adjudicators (72% vs. 54%), report a patient-important primary outcome (69% vs. 50%), report subgroup analyses (64% vs. 26%), prespecify subgroup hypotheses (42% vs. 20%), and report a test for interaction (54% vs. 27%); P < 0.05 for all differences. Conclusion RCTs published in higher impact journals were more likely to report methodological safeguards against bias and patient-important outcomes than those published in lower impact journals. However, sufficient limitations remain such that publication in a higher impact journal does not ensure low risk of bias.
In previous analyses, myocardial injury after noncardiac surgery, major bleeding, and sepsis were independently associated with most deaths in the 30 days after noncardiac surgery, but most of these ...deaths occurred during the index hospitalization for surgery. The authors set out to describe outcomes after discharge from hospital up to 1 yr after inpatient noncardiac surgery and associations between predischarge complications and postdischarge death up to 1 yr after surgery.
This study was an analysis of patients discharged after inpatient noncardiac surgery in a large international prospective cohort study across 28 centers from 2007 to 2013 of patients aged 45 yr or older followed to 1 yr after surgery. The study estimated (1) the cumulative postdischarge incidence of death and other outcomes up to a year after surgery and (2) the adjusted time-varying associations between postdischarge death and predischarge complications including myocardial injury after noncardiac surgery, major bleeding, sepsis, infection without sepsis, stroke, congestive heart failure, clinically important atrial fibrillation or flutter, amputation, venous thromboembolism, and acute kidney injury managed with dialysis.
Among 38,898 patients discharged after surgery, the cumulative 1-yr incidence was 5.8% (95% CI, 5.5 to 6.0%) for all-cause death and 24.7% (95% CI, 24.2 to 25.1%) for all-cause hospital readmission. Predischarge complications were associated with 33.7% (95% CI, 27.2 to 40.2%) of deaths up to 30 days after discharge and 15.0% (95% CI, 12.0 to 17.9%) up to 1 yr. Most of the association with death was due to myocardial injury after noncardiac surgery (15.6% 95% CI, 9.3 to 21.9% of deaths within 30 days, 6.4% 95% CI, 4.1 to 8.7% within 1 yr), major bleeding (15.0% 95% CI, 8.3 to 21.7% within 30 days, 4.7% 95% CI, 2.2 to 7.2% within 1 yr), and sepsis (5.4% 95% CI, 2.2 to 8.6% within 30 days, 2.1% 95% CI, 1.0 to 3.1% within 1 yr).
One in 18 patients 45 yr old or older discharged after inpatient noncardiac surgery died within 1 yr, and one quarter were readmitted to the hospital. The risk of death associated with predischarge perioperative complications persists for weeks to months after discharge.
Ventilator-induced lung injury (VILI) can occur as a result of mechanical ventilation to two lungs. Thoracic surgery often requires one-lung ventilation (OLV). The potential for VILI is likely higher ...in OLV. The impact of OLV on development of post-operative pulmonary complications is not well understood. We aimed to perform a scoping review to determine reliable biomarkers of VILI after OLV.
A scoping review was performed using Cochrane Collaboration methodology. We searched Medline, EMBASE and SCOPUS. Gray literature was searched. Studies of adult human or animal models without pre-existing lung damage exposed to OLV, with biomarker responses analyzed were included.
After screening 5,613 eligible papers, 89 papers were chosen for full text review, with 29 meeting inclusion. Approximately half (52%, n=15) of studies were conducted in humans in an intra-operative setting. Bronchoalveolar lavage (BAL) & serum analyses with enzyme-linked immunosorbent assay (ELISA)-based assays were most commonly used. The majority of analytes were investigated by a single study. Of the analytes that were investigated by two or more studies (n=31), only 16 were concordant in their findings. Across all sample types and studies 84% (n=66) of the 79 inflammatory markers and 75% (n=6) of the 8 anti-inflammatory markers tested were found to increase. Half (48%) of all studies showed an increase in TNF-α or IL-6.
A scoping review of the state of the evidence demonstrated that candidate biomarkers with the most evidence and greatest reliability are general markers of inflammation, such as IL-6 and TNF-α assessed using ELISA assays. Studies were limited in the number of biomarkers measured concurrently, sample size, and studies using human participants. In conclusion these identified markers can potentially serve as outcome measures for studies on OLV.
The Management of Myocardial Injury after Non-Cardiac Surgery (MANAGE) trial demonstrated that dabigatran 110 mg twice daily was more effective than placebo in preventing the primary composite ...outcome of vascular mortality, non-fatal myocardial infarction, non-hemorrhagic stroke, peripheral arterial thrombosis, amputation and symptomatic venous thromboembolism in patients with myocardial injury after non-cardiac surgery (MINS). The cost implications of dabigatran for this population are unknown but are important given the significant clinical implications.
Hospitalized events, procedures, and study and non-study medications were documented. We applied Canadian unit costs to healthcare resources consumed for all patients in the trial, and calculated the average cost per patient in Canadian dollars for the duration of the study (median follow-up of 16 months). A sensitivity analysis was performed using only Canadian patients, and subgroup analyses were also conducted.
The total study cost for the dabigatran group was $9985 per patient, compared with $10,082 for placebo, a difference of - $97 (95% confidence interval CI - $2128 to $3672). Savings arising from fewer clinical events and procedures in the dabigatran 110 mg twice-daily group were enough to offset the cost of the study drug. In Canadian patients, the difference was $250 (95% CI -$2848 to $4840). Both differences were considered cost neutral. Dabigatran 110 mg twice daily was cost saving or cost neutral in many subgroups that were considered.
Dabigatran 110 mg twice daily was cost neutral for patients in the MANAGE trial. Our cost findings support the use of dabigatran 110 mg twice daily in patients with MINS.
ClinicalTrials.gov identifier number NCT01661101.
Worldwide approximately 200 million adults undergo major surgery annually, of whom 8 million are estimated to suffer a myocardial injury after noncardiac surgery (MINS). There is currently no trial ...data informing the management of MINS. Antithrombotic agents such as direct oral anticoagulants might prevent major vascular complications in patients with MINS.
The Management of Myocardial Injury After Noncardiac Surgery (MANAGE) trial is a large international blinded randomized controlled trial of dabigatran vs placebo in patients who suffered MINS. We used a partial factorial design to also determine the effect of omeprazole vs placebo in reducing upper gastrointestinal bleeding and complications. Both study drugs were initiated in eligible patients within 35 days of suffering MINS and continued for a maximum of 2 years. The primary outcome is a composite of major vascular complications for the dabigatran trial and a composite of upper gastrointestinal complications for the omeprazole trial. We present the rationale and design of the trial and baseline characteristics of enrolled patients.
The trial randomized 1754 patients between January 2013 and July 2017. Patients' mean age was 69.9 years, 51.1% were male, 14.3% had a history of peripheral artery disease, 6.6% had a history of stroke or transient ischemic attack, 12.9% had a previous myocardial infarction, and 26.0% had diabetes. The diagnosis of MINS was on the basis of an isolated ischemic troponin elevation in 80.4% of participants.
MANAGE is the first randomized controlled trial to evaluate a potential treatment of patients who suffered MINS.
Chaque année à l’échelle mondiale, une intervention chirurgicale majeure est pratiquée chez environ 200 millions d’adultes. De ce nombre, quelque 8 millions subissent une lésion myocardique après une intervention chirurgicale non cardiaque (LMICNC). À l’heure actuelle, on ne dispose d’aucune donnée d’essais abordant la prise en charge des LMICNC. Des antithrombotiques comme les anticoagulants oraux directs pourraient prévenir les complications vasculaires majeures chez les patients présentant des LMICNC.
Management of Myocardial InjuryAfterNoncardiac Surgery (MANAGE), un vaste essai international contrôlé, à répartition aléatoire, mené à l’insu, visait à comparer le dabigatran et un placebo chez des patients ayant subi des LMICNC. Nous avons utilisé un modèle factoriel partiel afin de déterminer également l’effet de l’oméprazole, comparativement au placebo, sur la réduction des hémorragies et des complications gastro-intestinales hautes. L’administration du dabigatran et du placebo a été instaurée chez les patients admissibles moins de 35 jours après la survenue des LMICNC; elle s’est poursuivie sur une période qui pouvait aller jusqu’à 2 ans. Le résultat principal regroupe d’une part les complications vasculaires majeures sous dabigatran et d’autre part les complications gastro-intestinales hautes sous oméprazole. Nous présentons le fondement et la méthodologie de l’essai, ainsi que les caractéristiques initiales des patients inscrits.
Dans le cadre de l’essai, 1754 patients ont été répartis aléatoirement dans les groupes de traitement entre janvier 2013 et juillet 2017. Les patients étaient âgés en moyenne de 69,9 ans; 51,1 % étaient de sexe masculin; 14,3 % avaient des antécédents de maladie artérielle périphérique, 6,6 %, des antécédents d’accident vasculaire cérébral ou d'ischémie cérébrale transitoire, et 12,9 %, des antécédents d’infarctus du myocarde; 26,0 % étaient diabétiques. Le diagnostic de LMICNC se fondait sur une élévation isolée de la concentration de troponine dans un contexte ischémique chez 80,4 % des participants.
MANAGE est le premier essai contrôlé à répartition aléatoire évaluant un traitement potentiel des LMICNC.
Background Surgical jejunostomy tubes are a routine part of elective esophagectomies in patients with carcinomas and provide a route for nutritional support in those who experience complications. We ...wished to determine how frequently oral intake is delayed and the amount of nutrition delivered via the jejunostomy tube. Methods We reviewed the charts of all adults undergoing esophagectomy for carcinoma between January 2000 and June 2008. We determined the proportion of patients unable to resume oral nutrition after 8 days and the amount of nutrition delivered in each of the 8 days. Results In all, 111 patients underwent elective esophagectomy for carcinoma, and 103 had a jejunostomy tube placed. The mean age was 67 ± 10.8 years. The median time to oral intake was 7 (interquartile range 7–11) days. Seventy-four (67%) patients resumed oral intake within 8 days. The mean nutrition delivered by jejunostomy within the first 8 days as a percentage of the target was 45.6% (95% confidence interval 41.2%–49.9%). Six (5.4%) patients experienced complications attributable solely to the jejunostomy tube; 3 (2.9%) required surgery. Forty (38.8%) patients had abdominal issues serious enough to warrant delaying the progression of feeding. Conclusion Two-thirds of patients undergoing elective esophagectomy were tolerating oral intake by the end of the eighth postoperative day, and less than half of the target nutrition was delivered over the first 8 days. We now selectively place surgical jejunostomy tubes in patients undergoing elective esophagectomies.
Patients undergoing vascular procedures are prone to developing postoperative complications affecting their short‑term mortality. Prospective reports describing the incidence of long‑term ...complications after vascular surgery are lacking.
We aimed to describe the incidence of complications 1 year after vascular surgery and to evaluate an association between myocardial injury after noncardiac surgery (MINS) and 1‑year mortality.
This is a substudy of a large prospective cohort study Vascular Events in Noncardiac Surgery Patients Cohort Evaluation (VISION). Recruitment took place in 28 centers across 14 countries from August 2007 to November 2013. We enrolled patients aged 45 years or older undergoing vascular surgery, receiving general or regional anesthesia, and hospitalized for at least 1 night postoperatively. Plasma cardiac troponin T concentration was measured before the surgery and on the first, second, and third postoperative day. The patients or their relatives were contacted 1 year after the procedure to assess the incidence of major postoperative complications.
We enrolled 2641 patients who underwent vascular surgery, 2534 (95.9%) of whom completed 1‑year follow‑up. Their mean (SD) age was 68.2 (9.8) years, and the cohort was predominantly male (77.5%). The most frequent 1‑year complications were myocardial infarction (224/2534, 8.8%), amputation (187/2534, 7.4%), and congestive heart failure (67/2534, 2.6%). The 1‑year mortality rate was 8.8% (223/2534). MINS occurred in 633 patients (24%) and was associated with an increased 1‑year mortality (hazard ratio, 2.82; 95% CI, 2.14-3.72; P <0.001).
The incidence of major postoperative complications after vascular surgery is high. The occurrence of MINS is associated with a nearly 3‑fold increase in 1‑year mortality.
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