[Show abstract][Hide abstract] ABSTRACT: Background:
Meta-analyses of continuous outcomes typically provide enough information for decision-makers to evaluate the extent to which chance can explain apparent differences between interventions. The interpretation of the magnitude of these differences - from trivial to large - can, however, be challenging. We investigated clinicians' understanding and perceptions of usefulness of 6 statistical formats for presenting continuous outcomes from meta-analyses (standardized mean difference, minimal important difference units, mean difference in natural units, ratio of means, relative risk and risk difference).
We invited 610 staff and trainees in internal medicine and family medicine programs in 8 countries to participate. Paperbased, self-administered questionnaires presented summary estimates of hypothetical interventions versus placebo for chronic pain. The estimates showed either a small or a large effect for each of the 6 statistical formats for presenting continuous outcomes. Questions addressed participants' understanding of the magnitude of treatment effects and their perception of the usefulness of the presentation format. We randomly assigned participants 1 of 4 versions of the questionnaire, each with a different effect size (large or small) and presentation order for the 6 formats (1 to 6, or 6 to 1).
Overall, 531 (87.0%) of the clinicians responded. Respondents best understood risk difference, followed by relative risk and ratio of means. Similarly, they perceived the dichotomous presentation of continuous outcomes (relative risk and risk difference) to be most useful. Presenting results as a standardized mean difference, the longest standing and most widely used approach, was poorly understood and perceived as least useful.
None of the presentation formats were well understood or perceived as extremely useful. Clinicians best understood the dichotomous presentations of continuous outcomes and perceived them to be the most useful. Further initiatives to help clinicians better grasp the magnitude of the treatment effect are needed.
Canadian Medical Association Journal 10/2015; DOI:10.1503/cmaj.150430 · 5.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: We assessed the effectiveness of dual antiplatelet therapy (DAPT) post elective or urgent (i.e., post acute coronary syndrome [ACS]) coronary artery bypass graft surgery (CABG). Methods: We systematically searched MEDLINE, EMBASE, and the Cochrane Registry from inception to August 2015. Randomized controlled trials (RCTs) in adults undergoing CABG comparing either dual vs. single antiplatelet therapy or higher- vs. lower-intensity DAPT were identified. Results: Nine RCTs (n∈=∈4,887) with up to 1y follow-up were included. Five RCTs enrolled patients post-elective CABG (n∈=∈986). Two multi-centre RCTs enrolled ACS patients who subsequently underwent CABG (n∈=∈2,155). These 7 RCTs compared clopidogrel plus aspirin to aspirin alone. Two other multi-centre RCTs reported on ACS patients who subsequently underwent CABG comparing higher intensity DAPT with either ticagrelor (n∈=∈1,261) or prasugrel (n∈=∈485) plus aspirin to clopidogrel plus aspirin. Post-operative anti-platelet therapy was started when chest tube bleeding was no longer significant, typically within 24-48 h. There were no differences in all-cause mortality in clopidogrel plus aspirin vs. aspirin RCTs; conversely, all-cause mortality was significantly lower in ticagrelor and prasugrel vs. clopidogrel RCTs (risk ratio[RR] 0.49, 95 % confidence interval[CI] 0.33-0.71, p∈=∈0.0002; 2 RCTs, n∈=∈1695; I 2 ∈=∈0 %; interaction p∈<∈0.01 compared to clopidogrel plus aspirin vs aspirin RCTs). There were no differences in myocardial infarctions, strokes, or composite outcomes. Overall, major bleeding was not significantly increased (RR 1.31, 95 % CI 0.81-2.10, p∈=∈0.27; 7 RCTs, n∈=∈4500). There was heterogeneity (I 2 ∈ =∈42 %) due almost entirely to higher bleeding reported for the prasugrel RCT which included mainly CABG-related major bleeding (RR 3.15, 95 % CI 1.45-6.87, p∈=∈0.004; 1 RCT, n∈=∈437).
BMC Surgery 10/2015; 15(1). DOI:10.1186/s12893-015-0096-z · 1.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Colchicine has unique anti-inflammatory properties that may be beneficial in various cardiovascular conditions. This systematic review and meta-analysis of randomized controlled trials (RCTs) examines this issue.
We searched MEDLINE, EMBASE, and the Cochrane Database from inception to June 2014 for RCTs using colchicine in adult patients with cardiac diseases. Results were pooled using random effects.
15 RCTs (n = 3431 patients, median treatment 3 and follow-up 15 months) were included. All but 2 used colchicine 1 mg/day. In 5 trials, n = 1301) at risk for cardiovascular disease (coronary artery disease, acute coronary syndrome or stroke, post-angioplasty [2 RCTs], or congestive heart failure), colchicine reduced composite cardiovascular outcomes by ~60 % (risk ratio [RR] 0.44, 95 % confidence interval [CI] 0.28-0.69, p = 0.0004; I 2 = 0 %) and showed a trend towards lower all-cause mortality (RR 0.50, 95 % CI 0.23-1.08, p = 0.08; I 2 = 0 %). In pericarditis or post-cardiotomy, colchicine decreased recurrent pericarditis or post-pericardiotomy syndrome (RR 0.50, 95 % CI 0.41-0.60, p < 0.0001; I 2 = 0 %; 8 RCTs, n = 1635), and post-pericardiotomy or ablation induced atrial fibrillation (RR 0.65, 95 % CI 0.51-0.82, p = 0.0003; I 2 = 31 %; 4 RCTs, n = 1118). The most common adverse event was diarrhea. Treatment discontinuation overall and due to adverse events (RR 4.34, 95 % CI 1.70-11.07, p = 0.002; I 2 = 29 %; 7 RCTs, 83/790 [10.5 %] vs. 11/697 [1.6 %]) was higher in colchicine-assigned patients.
Current RCT data suggests that colchicine may reduce the composite rate of cardiovascular adverse outcomes in a range of patients with established cardiovascular disease. Furthermore, colchicine reduces rates of recurrent pericarditis, post-pericardiotomy syndrome, and peri-procedural atrial fibrillation following cardiac surgery. Further RCTs evaluating the potential of colchicine for secondary prevention of cardiovascular events would be of interest.
[Show abstract][Hide abstract] ABSTRACT: Sustained low efficiency dialysis (SLED) is increasingly used as a renal replacement modality in critically ill patients with acute kidney injury (AKI) and hemodynamic instability. SLED may reduce the hemodynamic perturbations of intermittent hemodialysis, while obviating the resource demands of CRRT. Although SLED is being increasingly used, few studies have evaluated its impact on clinical outcomes.
We conducted a cohort study comparing SLED (target 8 h/session, blood flow 200 mL/min, predominantly without anticoagulation) to CRRT in four ICUs at an academic medical centre. The primary outcome was mortality 30 days after RRT initiation, adjusted for demographics, comorbidity, baseline kidney function, and Sequential Organ Failure Assessment score. Secondary outcomes were persistent RRT dependence at 30 days and early clinical deterioration, defined as a rise in SOFA score or death 48 h after starting RRT.
We identified 158 patients who initiated treatment with CRRT and 74 with SLED. Mortality at 30 days was 54 % and 61 % among SLED- and CRRT-treated patients, respectively [adjusted odds ratio (OR) 1.07, 95 % CI 0.56-2.03, as compared with CRRT]. Among SLED recipients, the risk of RRT dependence at 30 days (adjusted OR 1.36, 95 % CI 0.51-3.57) and early clinical deterioration (adjusted OR 0.73, 95 % CI 0.40-1.34) were not different as compared to patients who initiated CRRT.
Notwithstanding the limitations of this small non-randomized study, we found similar clinical outcomes for patients treated with SLED and CRRT. While we await the completion of a trial that will definitively assess the non-inferiority of SLED as compared to CRRT, SLED appears to be an acceptable alternative form of renal support in hemodynamically unstable patients with AKI.
[Show abstract][Hide abstract] ABSTRACT: In patients with severe acute kidney injury (AKI) but no urgent indication for renal replacement therapy (RRT), the optimal time to initiate RRT remains controversial. While starting RRT preemptively may have benefits, this may expose patients to unnecessary RRT. To study this, we conducted a 12-center open-label pilot trial of critically ill adults with volume replete severe AKI. Patients were randomized to accelerated (12 h or less from eligibility) or standard RRT initiation. Outcomes were adherence to protocol-defined time windows for RRT initiation (primary), proportion of eligible patients enrolled, follow-up to 90 days, and safety in 101 fully eligible patients (57 with sepsis) with a mean age of 63 years. Median serum creatinine and urine output at enrollment were 268 micromoles/l and 356 ml per 24 h, respectively. In the accelerated arm, all patients commenced RRT and 45/48 did so within 12 h from eligibility (median 7.4 h). In the standard arm, 33 patients started RRT at a median of 31.6 h from eligibility, of which 19 did not receive RRT (6 died and 13 recovered kidney function). Clinical outcomes were available for all patients at 90 days following enrollment, with mortality 38% in the accelerated and 37% in the standard arm. Two surviving patients, both randomized to standard RRT initiation, were still RRT dependent at day 90. No safety signal was evident in either arm. Our findings can inform the design of a large-scale effectiveness randomized control trial.Kidney International advance online publication, 8 July 2015; doi:10.1038/ki.2015.184.
Kidney International 07/2015; 88(4). DOI:10.1038/ki.2015.184 · 8.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Extracorporeal carbon dioxide removal (ECCO2R) has been proposed for hypercapnic respiratory failure in chronic obstructive pulmonary disease (COPD) exacerbations, to avoid intubation or reduce length of invasive ventilation. Balance of risks, efficacy, and benefits of ECCO2R in patients with COPD is unclear.
We systematically searched MEDLINE and EMBASE to identify all publications reporting use of ECCO2R in COPD. We looked at physiological and clinical efficacy. A favorable outcome was defined as prevention of intubation or successful extubation. Major and minor complications were compiled.
We identified 3123 citations. Ten studies (87 patients), primarily case series, met inclusion criteria. ECCO2R prevented intubation in 65/70 (93 %) patients and assisted in the successful extubation of 9/17 (53 %) mechanically ventilated subjects. One case-control study matching to noninvasively ventilated controls reported lower intubation rates and hospital mortality with ECCO2R that trended toward significance. Physiological data comparing pre- to post-ECCO2R changes suggest improvements for pH (0.07-0.15 higher), PaCO2 (25 mmHg lower), and respiratory rate (7 breaths/min lower), but not PaO2/FiO2. Studies reported 11 major (eight bleeds requiring blood transfusion of 2 units, and three line-related complications, including one death related to retroperitoneal bleeding) and 30 minor complications (13 bleeds, five related to anticoagulation, and nine clotting-related device malfunctions resulting in two emergent intubations).
The technique is still experimental and no randomized trial is available. Recognizing selection bias associated with case series, there still appears to be potential for benefit of ECCO2R in patients with COPD exacerbations. However, it is associated with frequent and potentially severe complications. Higher-quality studies are required to better elucidate this risk-benefit balance.
Intensive Care Medicine 06/2015; 41(10). DOI:10.1007/s00134-015-3921-z · 7.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mechanical ventilation is a cornerstone in the management of acute respiratory failure (ARF). Both volume targeted and pressure targeted ventilations are used, the latter modes being increasingly used. We provide a narrative review of the physiological principles of these two types of breath delivery and performed a literature search and analyzed published comparisons between modes.
We performed a systematic review and meta-analysis to determine whether pressure control-continuous mandatory ventilation (PC-CMV) or inverse ratio PC-CMV (PC-IRV) has demonstrated advantages over volume control-continuous mandatory ventilation (VC-CMV). The Cochrane tool for risk of bias was used for methodological quality. We also introduced physiological criteria as quality indicators for selecting the studies. Outcomes included compliance, gas exchange, hemodynamics, work of breathing, and clinical outcomes. Analyses were completed with RevMan5 using random effects models.
34 studies met inclusion criteria, many being at high risk of bias. Comparisons of PC-CMV/PC-IRV and VC-CMV did not show any difference for compliance or gas exchange, even when looking at PC-IRV. Calculating the oxygenation index suggested a poorer effect for PC-IRV. There was no difference between modes in terms of hemodynamics, work of breathing, or clinical outcomes.
The two modes have different working principles but clinical available data do not suggest any difference in the outcomes. We included all identified trials, enhancing generalizability and attempted to include only sufficient quality physiological studies. However, included trials were small and varied considerably in quality. These data should help to open the choice of ventilation of patients with ARF.
[Show abstract][Hide abstract] ABSTRACT: To identify risk factors for failure of anticoagulant thromboprophylaxis in critically ill patients in the ICU.
Multivariable regression analysis of thrombosis predictors from a randomized thromboprophylaxis trial.
Sixty-seven medical-surgical ICUs in six countries.
Three thousand seven hundred forty-six medical-surgical critically ill patients.
All patients received anticoagulant thromboprophylaxis with low-molecular-weight heparin or unfractionated heparin at standard doses.
Independent predictors for venous thromboembolism, proximal leg deep vein thrombosis, and pulmonary embolism developing during critical illness were assessed. A total of 289 patients (7.7%) developed venous thromboembolism. Predictors of thromboprophylaxis failure as measured by development of venous thromboembolism included a personal or family history of venous thromboembolism (hazard ratio, 1.64; 95% CI, 1.03-2.59; p = 0.04) and body mass index (hazard ratio, 1.18 per 10-point increase; 95% CI, 1.04-1.35; p = 0.01). Increasing body mass index was also a predictor for developing proximal leg deep vein thrombosis (hazard ratio, 1.25; 95% CI, 1.06-1.46; p = 0.007), which occurred in 182 patients (4.9%). Pulmonary embolism occurred in 47 patients (1.3%) and was associated with body mass index (hazard ratio, 1.37; 95% CI, 1.02-1.83; p = 0.035) and vasopressor use (hazard ratio, 1.84; 95% CI, 1.01-3.35; p = 0.046). Low-molecular-weight heparin (in comparison to unfractionated heparin) thromboprophylaxis lowered pulmonary embolism risk (hazard ratio, 0.51; 95% CI, 0.27-0.95; p = 0.034) while statin use in the preceding week lowered the risk of proximal leg deep vein thrombosis (hazard ratio, 0.46; 95% CI, 0.27-0.77; p = 0.004).
Failure of standard thromboprophylaxis using low-molecular-weight heparin or unfractionated heparin is more likely in ICU patients with elevated body mass index, those with a personal or family history of venous thromboembolism, and those receiving vasopressors. Alternate management or incremental risk reduction strategies may be needed in such patients.
Critical Care Medicine 12/2014; 43(2). DOI:10.1097/CCM.0000000000000713 · 6.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Enrollment of individual patients into more than one study has been poorly evaluated. The objective of this study was to describe the characteristics of patients, researchers and centers involved in coenrollment, studies precluding coenrollment, and the prevalence, patterns, predictors, and outcomes of coenrollment in a randomized clinical trial.
Critical Care Medicine 11/2014; 43(2). DOI:10.1097/CCM.0000000000000692 · 6.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background We assessed the effectiveness of dual antiplatelet therapy (DAPT) post elective or urgent (i.e., post acute coronary syndrome [ACS]) coronary artery bypass graft surgery (CABG). Methods We systematically searched MEDLINE, EMBASE, and the Cochrane Registry from inception to August 2015. Randomized controlled trials (RCTs) in adults undergoing CABG comparing either dual vs. single antiplatelet therapy or higher- vs. lower-intensity DAPT were identified. Results Nine RCTs (n = 4,887) with up to 1y follow-up were included. Five RCTs enrolled patients post-elective CABG (n = 986). Two multi-centre RCTs enrolled ACS patients who subsequently underwent CABG (n = 2,155). These 7 RCTs compared clopidogrel plus aspirin to aspirin alone. Two other multi-centre RCTs reported on ACS patients who subsequently underwent CABG comparing higher intensity DAPT with either ticagrelor (n = 1,261) or prasugrel (n = 485) plus aspirin to clopidogrel plus aspirin. Post-operative anti-platelet therapy was started when chest tube bleeding was no longer significant, typically within 24–48 h. There were no differences in all-cause mortality in clopidogrel plus aspirin vs. aspirin RCTs; conversely, all-cause mortality was significantly lower in ticagrelor and prasugrel vs. clopidogrel RCTs (risk ratio[RR] 0.49, 95 % confidence interval[CI] 0.33–0.71, p = 0.0002; 2 RCTs, n = 1695; I 2 = 0 %; interaction p < 0.01 compared to clopidogrel plus aspirin vs aspirin RCTs). There were no differences in myocardial infarctions, strokes, or composite outcomes. Overall, major bleeding was not significantly increased (RR 1.31, 95 % CI 0.81–2.10, p = 0.27; 7 RCTs, n = 4500). There was heterogeneity (I 2 = 42 %) due almost entirely to higher bleeding reported for the prasugrel RCT which included mainly CABG-related major bleeding (RR 3.15, 95 % CI 1.45–6.87, p = 0.004; 1 RCT, n = 437). Conclusions Most RCT data for DAPT post CABG is derived from subgroups of ACS patients in DAPT RCTs requiring CABG who resume DAPT post-operatively. Limited RCT data with heterogeneous trial designs suggest that higher intensity (prasugrel or ticagrelor) but not lower intensity (clopidogrel) DAPT is associated with an approximate 50 % lower mortality in ACS patients who underwent CABG based on post-randomization subsets from single RCTs. Large prospective RCTs evaluating the use of DAPT post-CABG are warranted to provide more definitive guidance for clinicians.
The Canadian journal of cardiology 10/2014; 30(10):S160. DOI:10.1016/j.cjca.2014.07.242 · 3.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: IntroductionPatients with severe acute kidney injury (AKI) who are hospitalized at centres that do not provide renal replacement therapy (RRT) are frequently subjected to inter-hospital transfer for the provision of RRT. It is unclear whether such transfers are associated with worse patient outcomes as compared to the receipt of initial care in a centre that provides RRT. This study examined the relationship between inter-hospital transfer and 30-day mortality among critically ill patients with AKI who received RRT.Methods
We conducted a retrospective cohort study of all critically ill patients who commenced RRT for AKI at two academic hospitals in Toronto, Canada. The exposure of interest was inter-hospital transfer for the administration of RRT. We evaluated the relationship between transfer status and 30-day mortality (primary outcome) and RRT dependence at 30 days following RRT initiation (secondary outcome) respectively, using multivariate logistic regression with adjustment for patient demographics, clinical factors, biochemical indices and severity of illness.ResultsOf 370 patients who underwent RRT for AKI, 82 (22.2%) were transferred for this purpose from another hospital. Compared to non-transferred patients who started RRT, transferred patients were younger (61¿±¿15 versus 65¿±¿15 years, P¿=¿0.03) and had a higher serum creatinine concentration at RRT initiation (474¿±¿295 versus 365¿±¿169 ¿mol/L, P¿=¿0.002). Inter-hospital transfer was not associated with mortality (adjusted OR 0.61, 95% CI 0.33 to 1.12) or RRT-dependence (adjusted OR 1.64, 95% CI 0.70 to 3.81) at 30 days.Conclusions
Within the limitations of this observational study and the potential for residual confounding, inter-hospital transfer of critically ill patients with AKI was not associated with a higher risk of death or dialysis dependence 30 days after the initiation of acute RRT.
[Show abstract][Hide abstract] ABSTRACT: The process of discontinuing mechanical ventilation is known as weaning. During weaning, the work of breathing is transferred from the ventilator to the patient. Weaning is typically achieved by clinicians reducing ventilator support and/or conducting tests to determine whether a patient can breathe on his/her own. SmartCare™ is a unique system that automates this process by measuring selected respiratory variables, adapting ventilator output to meet individual patient needs and automatically conducting tests of spontaneous breathing to determine the earliest time when patients can breathe on their own. We identified 10 trials of moderate quality involving 654 participants and comparing SmartCare™ versus non-automated weaning strategies. Compared with non-automated strategies, SmartCare™ significantly decreased weaning time, time to successful removal from breathing machines and time spent in the ICU, with fewer patients receiving breathing machine support for longer than seven days and 21 days, and no increase in adverse events. SmartCare™ also showed a favourable trend toward fewer patients receiving ventilation for longer than 14 days, with no increase in adverse events. Subgroup analyses suggested more beneficial effects on weaning time in trials comparing SmartCare™ to a protocolized weaning strategy versus a non-protocolized control strategy. Sensitivity analyses, which excluded two trials with high risk of bias, supported significant reductions in weaning time with SmartCare™.
[Show abstract][Hide abstract] ABSTRACT: Restrictive red cell transfusion is recommended to minimize risk associated with exposure to allogeneic blood. However, perioperative anemia is an independent risk factor for adverse outcomes after cardiovascular surgery. The purpose of this systematic review and meta-analysis is to determine whether perioperative restrictive transfusion thresholds are associated with inferior clinical outcomes in randomized trials of cardiovascular surgery patients.
Critical Care Medicine 08/2014; 42(12). DOI:10.1097/CCM.0000000000000548 · 6.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Mechanical ventilation in the prone position is used to improve oxygenation and to mitigate the harmful effects of mechanical ventilation in patients with acute respiratory distress syndrome (ARDS). We sought to determine the effect of prone positioning on mortality among patients with ARDS receiving protective lung ventilation.
We searched electronic databases and conference proceedings to identify relevant randomized controlled trials (RCTs) published through August 2013. We included RCTs that compared prone and supine positioning during mechanical ventilation in patients with ARDS. We assessed risk of bias and obtained data on all-cause mortality (determined at hospital discharge or, if unavailable, after longest follow-up period). We used random-effects models for the pooled analyses.
We identified 11 RCTs (n=2341) that met our inclusion criteria. In the 6 trials (n=1016) that used a protective ventilation strategy with reduced tidal volumes, prone positioning significantly reduced mortality (risk ratio 0.74, 95% confidence interval 0.59-0.95; I2=29%) compared with supine positioning. The mortality benefit remained in several sensitivity analyses. The overall quality of evidence was high. The risk of bias was low in all of the trials except one, which was small. Statistical heterogeneity was low (I2<50%) for most of the clinical and physiologic outcomes.
Our analysis of high-quality evidence showed that use of the prone position during mechanical ventilation improved survival among patients with ARDS who received protective lung ventilation.
Canadian Medical Association Journal 05/2014; 186(10). DOI:10.1503/cmaj.140081 · 5.96 Impact Factor