Publications by authors named "Farid Foroutan"

64 Publications

Clinical Trials in COVID-19 Management & Prevention: A Meta-epidemiological Study examining.

J Clin Epidemiol 2021 Jul 15. Epub 2021 Jul 15.

Department of Health Research Methods, Evidence and Impact, McMaster University, 1280 Main St. West, Hamilton, Ontario, L8S 4L8, Canada; Department of Medicine, McMaster University, 1280 Main St. West, Hamilton, Ontario, L8S 4L8, Canada.

Objective: To describe the characteristics of Covid-19 randomized clinical trials (RCTs) and examine the association between trial characteristics and the likelihood of finding a significant effect.

Study Design: We conducted a systematic review to identify RCTs (up to October 21, 2020) evaluating drugs or blood products to treat or prevent Covid-19. We extracted trial characteristics (number of centres, funding sources, and sample size) and assessed risk of bias (RoB) using the Cochrane RoB 2.0 tool. We performed logistic regressions to evaluate the association between RoB due to randomization, single vs. multicentre, funding source, and sample size, and finding a statistically significant effect.

Results: We included 91 RCTs (n=46,802); 40 (44%) were single-centre, 23 (25.3%) enrolled <50 patients, 28 (30.8%) received industry funding, and 75 (82.4%) had high or probably high RoB. Thirty-eight trials (41.8%) reported a statistically significant effect. RoB due to randomization and being a single-centre trial were associated with increased odds of finding a statistically significant effect.

Conclusions: There is high variability in RoB among Covid-19 trials. Researchers, funders, and knowledge-users should be cognizant of the impact of RoB due to randomization and single-centre trial status in designing, evaluating, and interpreting the results of RCTs.

Registration: CRD42020192095.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jclinepi.2021.07.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280397PMC
July 2021

Prognostic value of natriuretic peptides in heart failure: systematic review and meta-analysis.

Heart Fail Rev 2021 Jul 5. Epub 2021 Jul 5.

Ted Rogers Center for Heart Research, University Health Network, Toronto, ON, Canada.

Risk models, informing optimal long-term medical management, seldom use natriuretic peptides (NP) in ascertaining the absolute risk of outcomes for HF patients. Individual studies evaluating the prognostic value of NPs in HF patients have reported varying effects, arriving at best estimates requires a systematic review. We systematically summarized the best evidence regarding the prognostic value of brain natriuretic peptide (BNP) and NT-proBNP in predicting mortality and hospitalizations in ambulatory heart failure (HF) patients. We searched bibliographic databases from 2005 to 2018 and included studies evaluating the association of BNP or NT-proBNP with mortality or hospitalization using multivariable Cox proportional hazard models. We pooled hazard ratios using random-effect models, explored heterogeneity using pre-specified subgroup analyses, and evaluated the certainty of evidence using the Grading of Recommendations and Development Evaluation framework. We identified 67 eligible studies reporting on 76,178 ambulatory HF patients with a median BNP of 407 pg/mL (261-574 pg/mL). Moderate to high-quality evidence showed that a 100-pg/mL increase in BNP was associated with a 14% increased hazard of mortality (HR 1.14, 95% CI 1.06-1.22); a 1-log-unit increase was associated with a 51% increased hazard of mortality (HR 1.51, 95% CI 1.41-1.61) and 48% increased hazard of mortality or hospitalization (HR 1.48, 95% CI 1.29-1.69). With moderate to high certainty, we observed a 14% independent relative increase in mortality, translating to a clinically meaningful increase in absolute risk even for low-risk patients. The observed associations may help in developing more accurate risk models that incorporate NPs and accurately prognosticate HF patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10741-021-10136-3DOI Listing
July 2021

Prognostic association of frailty with post-arrest outcomes following cardiac arrest: A systematic review and meta-analysis.

Resuscitation 2021 Jun 21. Epub 2021 Jun 21.

Ted Rogers Centre for Heart Research, University Health Network, 661 University Ave, Toronto, Ontario M5G 1X8, Canada. Electronic address:

Objective: To synthesize the current evidence examining the association between frailty and a series of post-arrest outcomes following the provision of cardiopulmonary resuscitation (CPR).

Data Sources: We searched MEDLINE, PubMed (exclusive of MEDLINE), EMBASE, CINAHL, and Web of Science from inception to August 2020 for observational studies that examined an association between frailty and post-arrest health outcomes, including in-hospital and post-discharge mortality. We conducted citation tracking for all eligible studies.

Study Selection: Our search yielded 20,480 citations after removing duplicate records. We screened titles, abstracts and full-texts independently and in duplicate.

Data Extraction: The prognosis research strategy group (PROGRESS) and the critical appraisal and data extraction for systematic review of prediction modelling studies (CHARMS) guidelines were followed. Study and outcome-specific risk of bias were assessed using the Quality in Prognosis Studies (QUIPS) instrument. We rated the certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) recommendations for prognostic factor research.

Data Synthesis: Four studies were included in this review and three were eligible for statistical pooling. Our sample comprised 1,134 persons who experienced in-hospital cardiac arrest (IHCA). The mean age of the sample was 71 years. The study results were pooled according to the specific frailty instrument. Three studies used the Clinical Frailty Scale (CFS) and adjusted age (our minimum confounder); the presence of frailty was associated with an approximate three-fold increase in the odds of dying in-hospital after IHCA (aOR = 2.93; 95% CI = 2.43-3.53, high certainty). Frailty was also associated with decreased incidence of ROSC (return of spontaneous circulation) and discharge home following IHCA. One study with high risk of bias used the Hospital Frailty Risk Score and reported a 43% decrease in the odds of discharge home for patients with frailty following IHCA.

Conclusion: High certainty evidence was found for an association between frailty and in-hospital mortality following IHCA. Frailty is a robust prognostic factor that contributes valuable information and can inform shared-decision making and policies surrounding advance care directives. Registration: PROSPERO Registration # CRD42020212922.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.resuscitation.2021.06.009DOI Listing
June 2021

Predictors of Mortality in Patients Treated with Veno-Arterial ECMO for Cardiogenic Shock Complicating Acute Myocardial Infarction: a Systematic Review and Meta-Analysis.

J Cardiovasc Transl Res 2021 Jun 3. Epub 2021 Jun 3.

Division of Cardiology, Peter Munk Cardiac Center, University of Toronto, Toronto, ON, Canada.

Background: Mortality for patients on veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for cardiogenic shock (CS) complicating acute myocardial infarction (AMI) remains high. This meta-analysis aims to identify factors that predict higher risk of mortality after VA-ECMO for AMI.

Methods: We meta-analyzed mortality after VA-ECMO for CS complicating AMI and the effect of factors from systematically selected studies published after 2009.

Results: 72 studies (10,276 patients) were included with a pooled mortality estimate of 58 %. With high confidence in estimates, failure to achieve TIMI III flow and left main culprit were identified as factors associated with higher mortality. With low-moderate confidence, older age, high BMI, renal dysfunction, increasing lactate, prothrombin activity < 50%, VA-ECMO implantation after revascularization, and non-shockable ventricular arrythmias were identified as factors associated with mortality.

Conclusion: These results provide clinicians with a framework for selecting patients for VA-ECMO for CS complicating AMI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12265-021-10140-wDOI Listing
June 2021

SGLT-2 inhibitors or GLP-1 receptor agonists for adults with type 2 diabetes: a clinical practice guideline.

BMJ 2021 05 11;373:n1091. Epub 2021 May 11.

Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada

Clinical Question: What are the benefits and harms of sodium-glucose cotransporter 2 (SGLT-2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists when added to usual care (lifestyle interventions and/or other diabetes drugs) in adults with type 2 diabetes at different risk for cardiovascular and kidney outcomes?

Current Practice: Clinical decisions about treatment of type 2 diabetes have been led by glycaemic control for decades. SGLT-2 inhibitors and GLP-1 receptor agonists are traditionally used in people with elevated glucose level after metformin treatment. This has changed through trials demonstrating atherosclerotic cardiovascular disease (CVD) and chronic kidney disease (CKD) benefits independent of medications' glucose-lowering potential.

Recommendations: The guideline panel issued risk-stratified recommendations concerning the use of SGLT-2 inhibitors or GLP-1 receptor agonists in adults with type 2 diabetes• Three or fewer cardiovascular risk factors without established CVD or CKD: Weak recommendation against starting SGLT-2 inhibitors or GLP-1 receptor agonists.• More than three cardiovascular risk factors without established CVD or CKD: Weak recommendation for starting SGLT-2 inhibitors and weak against starting GLP-1 receptor agonists.• Established CVD or CKD: Weak recommendation for starting SGLT-2 inhibitors and GLP-1 receptor agonists.• Established CVD and CKD: Strong recommendation for starting SGLT-2 inhibitors and weak recommendation for starting GLP-1 receptor agonists.• For those committed to further reducing their risk for CVD and CKD outcomes: Weak recommendation for starting SGLT-2 inhibitors rather than GLP-1 receptor agonists.

How This Guideline Was Created: An international panel including patients, clinicians, and methodologists created these recommendations following standards for trustworthy guidelines and using the GRADE approach. The panel applied an individual patient perspective.

The Evidence: A linked systematic review and network meta-analysis (764 randomised trials included 421 346 participants) of benefits and harms found that SGLT-2 inhibitors and GLP-1 receptor agonists generally reduce overall death, and incidence of myocardial infarctions, and end-stage kidney disease or kidney failure (moderate to high certainty evidence). These medications exert different effects on stroke, hospitalisations for heart failure, and key adverse events in different subgroups. Absolute effects of benefit varied widely based on patients' individual risk (for example, from five fewer deaths in the lowest risk to 48 fewer deaths in the highest risk, for 1000 patients treated over five years). A prognosis review identified 14 eligible risk prediction models, one of which (RECODe) informed most baseline risk estimates in evidence summaries to underpin the risk-stratified recommendations. Concerning patients' values and preferences, the recommendations were supported by evidence from a systematic review of published literature, a patient focus group study, a practical issues summary, and a guideline panel survey.

Understanding The Recommendation: We stratified the recommendations by the levels of risk for CVD and CKD and systematically considered the balance of benefits, harms, other considerations, and practical issues for each risk group. The strong recommendation for SGLT-2 inhibitors in patients with CVD and CKD reflects what the panel considered to be a clear benefit. For all other adults with type 2 diabetes, the weak recommendations reflect what the panel considered to be a finer balance between benefits, harms, and burdens of treatment options. Clinicians using the guideline can identify their patient's individual risk for cardiovascular and kidney outcomes using credible risk calculators such as RECODe. Interactive evidence summaries and decision aids may support well informed treatment choices, including shared decision making.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmj.n1091DOI Listing
May 2021

Incidence and impact of primary graft dysfunction in adult heart transplant recipients: A systematic review and meta-analysis.

J Heart Lung Transplant 2021 Jul 20;40(7):642-651. Epub 2021 Mar 20.

Peter Munk Cardiac Center, Toronto General Hospital-University Health Network, Ontario, Canada; Department of Health Research Methods, Evidence, and Impact, McMaster University, Ontario, Canada. Electronic address:

Purpose: Primary graft dysfunction (PGD) is a leading cause of early mortality after heart transplant (HTx). To identify PGD incidence and impact on mortality, and to elucidate risk factors for PGD, we systematically reviewed studies using the ISHLT 2014 Consensus Report definition and reporting the incidence of PGD in adult HTx recipients.

Methods: We conducted a systematic search in January 2020 including studies reporting the incidence of PGD in adult HTx recipients. We used a random effects model to pool the incidence of PGD among HTx recipients and, for each PGD severity, the mortality rate among those who developed PGD. For prognostic factors evaluated in ≥2 studies, we used random effects meta-analyses to pool the adjusted odds ratios for development of PGD. The GRADE framework informed our certainty in the evidence.

Results: Of 148 publications identified, 36 observational studies proved eligible. With moderate certainty, we observed pooled incidences of 3.5%, 6.6%, 7.7%, and 1.6% and 1-year mortality rates of 15%, 21%, 41%, and 35% for mild, moderate, severe and isolated right ventricular-PGD, respectively. Donor factors (female sex, and undersized), recipient factors (creatinine, and pre-HTx use of amiodarone, and temporary or durable mechanical support), and prolonged ischemic time proved associated with PGD post-HTx.

Conclusion: Our review suggests that the incidence of PGD may be low but its risk of mortality high, increasing with PGD severity. Prognostic factors, including undersized donor, recipient use of amiodarone pre-HTx and recipient creatinine may guide future studies in exploring donor and/or recipient selection and risk mitigation strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.healun.2021.03.015DOI Listing
July 2021

Antemortem Heparin in Organ Donation after Circulatory Death Determination (DCDD): A Systematic Review of the Literature.

Transplantation 2021 Apr 21. Epub 2021 Apr 21.

Division of Critical Care, Department of Medicine, Western University, London, Canada Department of Internal Medicine, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates. Ted Rogers Centre for Heart Research, Peter Munk Cardiac Center, Toronto, Canada Division of Critical Care, Department of Medicine, McMaster University Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Canada Division of Cardiology, Department of Medicine, McMaster University Population Health Research Institute, Hamilton, Canada Department of Anesthesiology, Université de Sherbrooke, Quebec, Canada Department of Epidemiology and Biostatistics, Western University, London, Canada Department of Surgery and Microbiology and Immunology, Schulich School of Medicine & Dentistry, Western University, London, Canada Multi-Organ Transplant Program, Department of Surgery, Toronto General Hospital, Toronto, Canada Department of Medicine, McMaster University, Hamilton, Canada.

Donation after circulatory death determination (DCDD) frequently involves antemortem heparin administration to mitigate peri-arrest microvascular thrombosis. We systematically reviewed the literature to: (1) describe heparin administration practices, and (2) explore the effects on transplant outcomes. We searched MEDLINE and EMBASE for studies reporting DCDD heparin practices including use, dosage, and timing (Objective 1). To explore associations between antemortem heparin and transplant outcomes (Objective 2), we (i) summarized within-study comparisons and (ii) used meta-regression analyses to examine associations between proportions of donors that received heparin and transplant outcomes. We assessed risk of bias using the Newcastle Ottawa Scale and applied the GRADE methodology to determine certainty in the evidence. For Objective 1, among 55 eligible studies, 48 reported heparin administration to at least some donors (range: 15.8% to 100%) at variable doses (up to 1000 units/kg) and times relative to withdrawal of life sustaining therapy. For Objective 2, seven studies that directly compared liver transplants with and without antemortem heparin reported lower rates of primary nonfunction, hepatic artery thrombosis, graft failure at 5 years, or recipient mortality (low certainty of evidence). In contrast, meta-regression analysis of 32 liver transplant studies detected no associations between the proportion of donors that received heparin and rates of early allograft dysfunction, primary nonfunction, hepatic artery thrombosis, biliary ischemia, graft failure, re-transplantation, or patient survival (very low certainty of evidence). In conclusion, antemortem heparin practices vary substantially with an uncertain effect on transplant outcomes. Given the controversies surrounding antemortem heparin, clinical trials may be warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TP.0000000000003793DOI Listing
April 2021

Predictive models for cardiovascular and kidney outcomes in patients with type 2 diabetes: systematic review and meta-analyses.

Heart 2021 Apr 8. Epub 2021 Apr 8.

Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada

Objective: To inform a clinical practice guideline (BMJ Rapid Recommendations) considering sodium glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists for treatment of adults with type 2 diabetes, we summarised the available evidence regarding the performance of validated risk models on cardiovascular and kidney outcomes in these patients.

Methods: We systematically searched bibliographic databases in January 2020 to identify observational studies evaluating risk models for all-cause and cardiovascular mortality, heart failure (HF) hospitalisations, end-stage kidney disease (ESKD), myocardial infarction (MI) and ischaemic stroke in ambulatory adults with type 2 diabetes. Using a random effects model, we pooled discrimination measures for each model and outcome, separately, and descriptively summarised calibration plots, when available. We used the Prediction Model Risk of Bias Assessment Tool to assess risk of bias of each included study and the Grading of Recommendations, Assessment, Development, and Evaluation approach to evaluate our certainty in the evidence.

Results: Of 22 589 publications identified, 15 observational studies reporting on seven risk models proved eligible. Among the seven models with >1 validation cohort, the Risk Equations for Complications of Type 2 Diabetes (RECODe) had the best calibration in primary studies and the highest pooled discrimination measures for the following outcomes: all-cause mortality (C-statistics 0.75, 95% CI 0.70 to 0.80; high certainty), cardiovascular mortality (0.79, 95% CI 0.75 to 0.84; low certainty), ESKD (0.73, 95% CI 0.52 to 0.94; low certainty), MI (0.72, 95% CI 0.69 to 0.74; moderate certainty) and stroke (0.71, 95% CI 0.68 to 0.74; moderate certainty). This model does not, however, predict risk of HF hospitalisations.

Conclusion: Of available risk models, RECODe proved to have satisfactory calibration in primary validation studies and acceptable discrimination superior to other models, though with high risk of bias in most primary studies.

Trial Registration Number: CRD42020168351.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/heartjnl-2021-319243DOI Listing
April 2021

Association between routine measures of graft function and mortality in heart transplant recipients.

Heart 2021 Mar 11. Epub 2021 Mar 11.

Cardiology, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.

Objective: To date, long-term graft dysfunction, an important cause of death after heart transplantation, has been defined as a left ventricular ejection fraction (LVEF) of ≤40% or right atrial pressure (RAP) of ≥15 mm Hg. Empirical associations between measures of cardiac function and mortality post-transplant remain, however, unestablished.

Methods: We conducted a retrospective two-centre cohort study of consecutive adults who underwent heart transplant between 2002 and 2017. We evaluated the association between LVEF and RAP and mortality, including rejection and cardiac allograft vasculopathy as additional time-dependent covariates using Cox proportional hazard models. We applied restricted cubic splines to both LVEF and RAP.

Results: Of 590 eligible heart transplant recipients, of whom 72% were male with a mean age of 49 years, 410 received their transplant at Toronto General Hospital and 180 at Rigshospitalet. We observed a 5% absolute risk increase for 1-year mortality, from 11% to 16%, when the LVEF dropped to 53% (HR 1.71 for LVEF of 53% compared with 60%, 95% CI 1.36 to 2.14) or when the RAP increased to 12 mm Hg (HR 1.49 for RAP of 12 mm Hg compared with 5 mm Hg, 95% CI 1.04 to 2.13).

Conclusion: In this study, we observed that small changes in graft function at any time post-transplant are associated with an increased mortality. Our results suggest that the current definition of graft dysfunction may underestimate patient risk of adverse outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/heartjnl-2020-318721DOI Listing
March 2021

Prognostic value of blood pressure in ambulatory heart failure: a meta-analysis and systematic review. Ambulatory blood pressure predicts heart failure prognosis.

Heart Fail Rev 2021 Mar 8. Epub 2021 Mar 8.

Ted Rogers Centre for Heart Research, University Health Network, Toronto, ON, Canada.

Previous primary studies have explored the association between blood pressure (BP) and mortality in ambulatory heart failure (HF) patients reporting varying and contrasting associations. The aim is to determine the pooled BP prognostic value and explore potential reasons for between-study inconsistency. We searched Medline, Cochrane, EMBASE and CINAHL from January 2005 to October 2018 for studies with ≥ 50 events (mortality and/or hospitalization) and included BP in a multivariable model in ambulatory HF patients. We pooled hazard ratios (random effects model) for systolic BP (SBP) or diastolic BP (DBP) effect on mortality and/or hospitalization risk. We used a priori defined sub-group analyses to explore heterogeneity and GRADE approach to assess the certainty of the evidence. Seventy-one eligible articles (239,467 screened) at low to moderate risk of bias included 235,752 participants. Higher SBP was associated with reduced all-cause mortality (HR 0.93, 95%CI 0.91-0.95, I = 87.13%, moderate certainty), all-cause hospitalization events (HR 0.91, 95%CI 0.88-0.93, I = 44.4%, high certainty) and their composite endpoint (HR 0.93 per 10 mmHg, 95%CI 0.91-0.94, I = 86.3%, high certainty). DBP did not demonstrate a statistically significant effect for all outcomes. The association strength was significantly weaker in studies following patients with either LVEF > 40%, higher average SBP (> 130 mmHg), increasing age and diabetes. All other a priori subgroup hypotheses did not explain between study differences. Higher ambulatory SBP is associated with reduced risk of all-cause mortality and hospitalization. Patients with lower BP and reduced LVEF are in a high-risk group of developing adverse events with moderate certainty of evidence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10741-021-10086-wDOI Listing
March 2021

Machine Learning Compared With Conventional Statistical Models for Predicting Myocardial Infarction Readmission and Mortality: A Systematic Review.

Can J Cardiol 2021 Mar 5. Epub 2021 Mar 5.

Ted Rogers Centre for Heart Research, Toronto, Ontario, Canada; Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada; Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada; Institute for Health Policy, Management and Evaluation, Toronto, Ontario, Canada; Toronto General Hospital Research Institute, Toronto, Ontario, Canada; University of Toronto, Toronto, Ontario, Canada. Electronic address:

Background: Machine learning (ML) methods are increasingly used in addition to conventional statistical modelling (CSM) for predicting readmission and mortality in patients with myocardial infarction (MI). However, the two approaches have not been systematically compared across studies of prognosis in patients with MI.

Methods: Following PRISMA guidelines, we systematically reviewed the literature via Medline, EPub, Cochrane Central, Embase, Inspec, ACM Digital Library, and Web of Science. Eligible studies included primary research articles published from January 2000 to March 2020, comparing ML and CSM for prognostication after MI.

Results: Of 7,348 articles, 112 underwent full-text review, with the final set composed of 24 articles representing 374,365 patients. ML methods included artificial neural networks (n = 12 studies), random forests (n = 11), decision trees (n = 8), support vector machines (n = 8), and Bayesian techniques (n = 7). CSM included logistic regression (n = 19 studies), existing CSM-derived risk scores (n = 12), and Cox regression (n = 2). Thirteen of 19 studies examining mortality reported higher C-indexes with the use of ML compared with CSM. One study examined readmissions at 2 different time points, with C-indexes that were higher for ML than CSM. Across all studies, a total of 29 comparisons were performed, but the majority (n = 26, 90%) found small (< 0.05) absolute differences in the C-index between ML and CSM. With the use of a modified CHARMS checklist, sources of bias were identifiable in the majority of studies, and only 2 were externally validated.

Conclusion: Although ML algorithms tended to have higher C-indexes than CSM for predicting death or readmission after MI, these studies exhibited threats to internal validity and were often unvalidated. Further comparisons are needed, with adherence to clinical quality standards for prognosis research. (Trial registration: PROSPERO CRD42019134896).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cjca.2021.02.020DOI Listing
March 2021

Mortality in patients with cardiogenic shock supported with VA ECMO: A systematic review and meta-analysis evaluating the impact of etiology on 29,289 patients.

J Heart Lung Transplant 2021 Apr 19;40(4):260-268. Epub 2021 Jan 19.

Ted Rogers Center of Excellence, Peter Munk Cardiac Centre, Toronto, Ontario, Canada.

Background: Venoarterial extracorporeal membrane oxygenation (VA ECMO) is associated with variable outcomes. In this meta-analysis, we evaluated the mortality after VA ECMO across multiple etiologies of cardiogenic shock (CS).

Methods: In June 2019, we performed a systematic search selecting observational studies with ≥10 adult patients reporting on short-term mortality (30-day or mortality at discharge) after initiation of VA ECMO by CS etiology published after 2009. We performed meta-analyses using random effect models and used metaregression to evaluate mortality across CS etiology.

Results: We included 306 studies (29,289 patients): 25 studies on after heart transplantation (HTx) (771 patients), 13 on myocarditis (906 patients), 33 on decompensated heart failure (HF) (3,567 patients), 64 on after cardiotomy shock (8,231 patients), 10 on pulmonary embolism (PE) (221 patients), 80 on acute myocardial infarction (AMI) (7,774 patients), and 113 on after cardiac arrest [CA] (7,814 patients). With moderate certainty on effect estimates, we observed significantly different mortality estimates for various etiologies (p < 0.001), which is not explained by differences in age and sex across studies: 35% (95% CI: 29-42) for after HTx, 40% (95% CI: 33-46) for myocarditis, 53% (95% CI: 46-59) for HF, 52% (95% CI: 38-66) for PE, 59% (95% CI: 56-63) for cardiotomy, 60% (95% CI: 57-64) for AMI, 64% (95% CI: 59-69) for post‒in-hospital CA, and 76% (95% CI: 69-82) for post-out‒of-hospital CA. Univariable metaregression showed that variation in mortality estimates within etiology group was partially explained by population age, proportion of females, left ventricle venting, and CA.

Conclusions: Using an overall estimate of mortality for patients with CS requiring VA ECMO is inadequate given the differential outcomes by etiology. To further refine patient selection and management to improve outcomes, additional studies evaluating patient characteristics impacting outcomes by specific CS etiology are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.healun.2021.01.009DOI Listing
April 2021

Minimal important difference estimates for patient-reported outcomes: A systematic survey.

J Clin Epidemiol 2021 May 13;133:61-71. Epub 2020 Dec 13.

Department of Health Research Methods, Evidence and Impact, McMaster University, 1280 Main St East, Hamilton, Ontario L8S 4L8, Canada; Department of Medicine, McMaster University, 1280 Main St East, Hamilton, Ontario L8S 4L8, Canada.

Objectives: The objective of the study was to develop an inventory summarizing all anchor-based minimal important difference (MID) estimates for patient-reported outcome measures (PROMs) available in the medical literature.

Study Design And Setting: We searched MEDLINE, EMBASE, CINAHL, PsycINFO, and the Patient-Reported Outcome and Quality of Life Instruments Database internal library (January 1989-October 2018). We included primary studies empirically calculating an anchor-based MID estimate for any PROM in adults and adolescents. Pairs of reviewers independently screened and selected studies, extracted data, and evaluated the credibility of the MIDs.

Results: We identified 585 eligible studies, the majority conducted in Europe (n = 211) and North America (n = 179), reporting 5,324 MID estimates for 526 distinct PROMs. Investigators conducted their studies in the context of patients receiving surgical (n = 105, 18%), pharmacological (n = 85, 15%), rehabilitation (n = 65, 11%), or a combination of interventions (n = 194, 33%). Of all MID estimates, 59% (n = 3,131) used a global rating of change anchor. Major credibility limitations included weak correlation (n = 1,246, 23%) or no information regarding the correlation (n = 3,498, 66%) between the PROM and anchor and imprecision in the MID estimate (n = 2,513, 47%).

Conclusion: A large number of MIDs for assisting in the interpretation of PROMs exist. The MID inventory will facilitate the use of MID estimates to inform the interpretation of the magnitude of treatment effects in clinical research and guideline development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jclinepi.2020.11.024DOI Listing
May 2021

Prognostic factors for severity and mortality in patients infected with COVID-19: A systematic review.

PLoS One 2020 17;15(11):e0241955. Epub 2020 Nov 17.

Fundación Epistemonikos, Santiago, Chile.

Background And Purpose: The objective of our systematic review is to identify prognostic factors that may be used in decision-making related to the care of patients infected with COVID-19.

Data Sources: We conducted highly sensitive searches in PubMed/MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL) and Embase. The searches covered the period from the inception date of each database until April 28, 2020. No study design, publication status or language restriction were applied.

Study Selection And Data Extraction: We included studies that assessed patients with confirmed or suspected SARS-CoV-2 infectious disease and examined one or more prognostic factors for mortality or disease severity. Reviewers working in pairs independently screened studies for eligibility, extracted data and assessed the risk of bias. We performed meta-analyses and used GRADE to assess the certainty of the evidence for each prognostic factor and outcome.

Results: We included 207 studies and found high or moderate certainty that the following 49 variables provide valuable prognostic information on mortality and/or severe disease in patients with COVID-19 infectious disease: Demographic factors (age, male sex, smoking), patient history factors (comorbidities, cerebrovascular disease, chronic obstructive pulmonary disease, chronic kidney disease, cardiovascular disease, cardiac arrhythmia, arterial hypertension, diabetes, dementia, cancer and dyslipidemia), physical examination factors (respiratory failure, low blood pressure, hypoxemia, tachycardia, dyspnea, anorexia, tachypnea, haemoptysis, abdominal pain, fatigue, fever and myalgia or arthralgia), laboratory factors (high blood procalcitonin, myocardial injury markers, high blood White Blood Cell count (WBC), high blood lactate, low blood platelet count, plasma creatinine increase, high blood D-dimer, high blood lactate dehydrogenase (LDH), high blood C-reactive protein (CRP), decrease in lymphocyte count, high blood aspartate aminotransferase (AST), decrease in blood albumin, high blood interleukin-6 (IL-6), high blood neutrophil count, high blood B-type natriuretic peptide (BNP), high blood urea nitrogen (BUN), high blood creatine kinase (CK), high blood bilirubin and high erythrocyte sedimentation rate (ESR)), radiological factors (consolidative infiltrate and pleural effusion) and high SOFA score (sequential organ failure assessment score).

Conclusion: Identified prognostic factors can help clinicians and policy makers in tailoring management strategies for patients with COVID-19 infectious disease while researchers can utilise our findings to develop multivariable prognostic models that could eventually facilitate decision-making and improve patient important outcomes.

Systematic Review Registration: Prospero registration number: CRD42020178802. Protocol available at: https://www.medrxiv.org/content/10.1101/2020.04.08.20056598v1.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241955PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671522PMC
December 2020

Exercise rehabilitation in cardiac resynchronization: systematic review and a meta-analysis.

Heart Fail Rev 2021 May 17;26(3):507-519. Epub 2020 Nov 17.

Division of Cardiology, Peter Munk Cardiac Centre, Toronto General Hospital, University Health Network, Toronto, Canada.

The benefit of exercise training in cardiac resynchronization therapy (CRT) recipients is not well established. We conducted a systematic review and meta-analysis to determine the effect of exercise training on clinical outcomes in CRT recipients.A comprehensive search until 2019 was conducted of MEDLINE, Epub, Embase, CINAHL and Cochrane databases as well as a bibliographic hand search to identify additional studies. We included all studies that compared aerobic exercise interventions in adults treated with CRT devices with adults treated with usual CRT care. These studies evaluated patient clinical characteristics, exercise testing measures, hemodynamic measures, echocardiography parameters, biomarkers and adverse events. Independent reviewers evaluated study eligibility, abstracted data and assessed risk of bias in duplicate. We used random-effect meta-analysis methods to estimate mean differences and odds ratios. Grades of Recommendation, Assessment, Development and Evaluation system were used to quantify absolute effects and quality of evidence. I was used to evaluate heterogeneity.We identified seven studies, six randomized control trials and one observational study, totaling 332 CRT patients in the exercise intervention and 534 patients receiving usual care. Peak VO was 2.4 ml/kg/min higher in the exercise group in comparison with the control group (pooled mean difference 2.26, 95% CI 1.38-3.13, I = 53%, high quality). AT-VO improved with exercise rehabilitation, and heterogeneity was considered low (pooled mean difference 3.96, 95% CI 2.68-5.24, I = 0.0%, moderate quality).Peak VO and AT-VO are increased with aerobic exercise in CRT recipients, demonstrating a significant improvement in functional capacity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10741-020-10049-7DOI Listing
May 2021

Preoperative prognostic factors associated with postoperative delirium in older people undergoing surgery: protocol for a systematic review and individual patient data meta-analysis.

Syst Rev 2020 11 14;9(1):261. Epub 2020 Nov 14.

PIPRA AG, Josefstrasse 219, 8005, Zürich, Switzerland.

Background: Early identification of patients at risk for postoperative delirium is essential because adequate well-timed interventions could reduce the occurrence of delirium and the related detrimental outcomes.

Methods: We will conduct a systematic review and individual patient data (IPD) meta-analysis of prognostic studies evaluating the predictive value of risk factors associated with an increased risk of postoperative delirium in elderly patients undergoing elective surgery. We will identify eligible studies through systematic search of MEDLINE, EMBASE, and CINAHL from their inception to May 2020. Eligible studies will enroll older adults (≥ 50 years) undergoing elective surgery and assess pre-operative prognostic risk factors for delirium and incidence of delirium measured by a trained individual using a validated delirium assessment tool. Pairs of reviewers will, independently and in duplicate, screen titles and abstracts of identified citations, review the full texts of potentially eligible studies. We will contact chief investigators of eligible studies requesting to share the IPD to a secured repository. We will use one-stage approach for IPD meta-analysis and will assess certainty of evidence using the GRADE approach.

Discussion: Since we are using existing anonymized data, ethical approval is not required for this study. Our results can be used to guide clinical decisions about the most efficient way to prevent postoperative delirium in elderly patients.

Systematic Review Registration: CRD42020171366 .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13643-020-01518-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666505PMC
November 2020

Resting Heart Rate as an Important Predictor of Mortality and Morbidity in Ambulatory Patients With Heart Failure: A Systematic Review and Meta-Analysis.

J Card Fail 2021 Mar 7;27(3):349-363. Epub 2020 Nov 7.

Ted Rogers Centre for Heart Research, University Health Network, Toronto, Ontario, Canada. Electronic address:

Background: Resting heart rate is a risk factor of adverse heart failure outcomes; however, studies have shown controversial results. This meta-analysis evaluates the association of resting heart rate with mortality and hospitalization and identifies factors influencing its effect.

Methods And Results: We systematically searched electronic databases in February 2019 for studies published in 2005 or before that evaluated the resting heart rate as a primary predictor or covariate of multivariable models of mortality and/or hospitalization in adult ambulatory patients with heart failure. Random effects inverse variance meta-analyses were performed to calculate pooled hazard ratios. The Grading of Recommendations, Assessment, Development and Evaluation approach was used to assess evidence quality. Sixty-two studies on 163,445 patients proved eligible. Median population heart rate was 74 bpm (interquartile range 72-76 bpm). A 10-bpm increase was significantly associated with increased risk of all-cause mortality (hazard ratio 1.10, 95% confidence interval 1.08-1.13, high quality). Overall, subgroup analyses related to patient characteristics showed no changes to the effect estimate; however, there was a strongly positive interaction with age showing increasing risk of all-cause mortality per 10 bpm increase in heart rate.

Conclusions: High-quality evidence demonstrates increasing resting heart rate is a significant predictor of all-cause mortality in ambulatory patients with heart failure on optimal medical therapy, with consistent effect across most patient factors and an increased risk trending with older age.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cardfail.2020.11.003DOI Listing
March 2021

Redo sternotomy versus left ventricular assist device explant as risk factors for early mortality following heart transplantation.

Interact Cardiovasc Thorac Surg 2020 11;31(5):603-610

Division of Cardiovascular Surgery, Peter Munk Cardiac Centre, Toronto General Hospital, University Health Network, University of Toronto, Toronto, ON, Canada.

Objectives: There is an increasing proportion of patients with a previous sternotomy (PS) or durable left ventricular assist device (LVAD) undergoing heart transplantation (HT). We hypothesized that patients with LVAD support at the time of HT have a lower risk than patients with PS and may have a comparable risk to patients with a virgin chest (VC).

Methods: This is a single-centre retrospective cohort study of all adults who underwent primary single-organ HT between 2002 and 2017. Multivariable Cox regression analyses were performed to compare 30-day and 1-year mortality between transplanted patients with a VC (VC-HT), a PS (PS-HT) or an LVAD explant (LVAD-HT).

Results: Three hundred seventy-nine patients were analysed (VC-HT: 196, PS-HT: 94, LVAD-HT: 89). A larger proportion of patients in the LVAD-HT group were males (83%), had blood group O (52%), non-ischaemic aetiology (70%) and sensitization (67%). The PS-HT group had a higher frequency of patients with congenital heart disease (30%) and PSs compared to LVAD-HT patients (P < 0.001). PS-HT and LVAD-HT patients required a longer bypass time (P < 0.001) and showed a greater estimated blood loss (P < 0.001). Postoperatively, LVAD-HT required haemodialysis more frequently than the VC-HT group (P = 0.031). Multivariable analyses found that PS-HT patients had increased 30-day mortality compared to VC-HT [hazard ratio (HR) 2.63, 95% confidence interval (CI) 1.15-6.01; P = 0.022] while LVAD-HT did not (HR 2.17, 95% CI 0.96-4.93; P = 0.064). At 1-year, neither PS-HT nor LVAD-HT groups were significantly associated with increased mortality compared to VC-HT.

Conclusions: Transplants in recipients with PS-HT demonstrated increased early mortality compared to VC-HT patients. Although LVAD explant is often technically challenging, this population demonstrated similar mortality compared to those VC-HT patients. The chronic and perioperative support provided by the LVAD may play a favourable role in early patient outcomes compared to other redo sternotomy patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/icvts/ivaa180DOI Listing
November 2020

Predicting the Risk of Right Ventricular Failure in Patients Undergoing Left Ventricular Assist Device Implantation: A Systematic Review.

Circ Heart Fail 2020 10 28;13(10):e006994. Epub 2020 Sep 28.

Heart Failure and Transplant Program, Peter Munk Cardiac Centre (M.M., J.K.K.V.-N., F.F., F.B., A.C.A.), University Health Network, Toronto, Canada.

Background: Right ventricular failure (RVF) is a cause of major morbidity and mortality after left ventricular assist device (LVAD) implantation. It is, therefore, integral to identify patients who may benefit from biventricular support early post-LVAD implantation. Our objective was to explore the performance of risk prediction models for RVF in adult patients undergoing LVAD implantation.

Methods: A systematic search was performed on Medline, Embase, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews from inception until August 2019 for all relevant studies. Performance was assessed by discrimination (via C statistic) and calibration if reported. Study quality was assessed using the Prediction Model Risk of Bias Assessment Tool criteria.

Results: After reviewing 3878 citations, 25 studies were included, featuring 20 distinctly derived models. Five models were derived from large multicenter cohorts: the European Registry for Patients With Mechanical Circulatory Support, Interagency Registry for Mechanically Assisted Circulatory Support, Kormos, Pittsburgh Bayesian, and Mechanical Circulatory Support Research Network RVF models. Seventeen studies (68%) were conducted in cohorts implanted with continuous-flow LVADs exclusively. The definition of RVF as an outcome was heterogenous among models. Seven derived models (28%) were validated in at least 2 cohorts, reporting limited discrimination (C-statistic range, 0.53-0.65). Calibration was reported in only 3 studies and was variable.

Conclusions: Existing RVF prediction models exhibit heterogeneous derivation and validation methodologies, varying definitions of RVF, and are mostly derived from single centers. Validation studies of these prediction models demonstrate poor-to-modest discrimination. Newer models are derived in cohorts implanted with continuous-flow LVADs exclusively and exhibit modest discrimination. Derivation of enhanced discriminatory models and their validations in multicenter cohorts is needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.006994DOI Listing
October 2020

Predictors of Prolonged Opioid Use After Initial Prescription for Acute Musculoskeletal Injuries in Adults : A Systematic Review and Meta-analysis of Observational Studies.

Ann Intern Med 2020 11 18;173(9):721-729. Epub 2020 Aug 18.

Michael G. DeGroote National Pain Centre, McMaster University, and Chronic Pain Centre of Excellence for Canadian Veterans, Hamilton, Ontario, Canada (J.W.B.).

Background: Opioids are frequently prescribed for acute musculoskeletal injuries and may result in long-term use and consequent harms.

Purpose: To explore factors associated with persistent opioid use after its prescription for acute musculoskeletal injury.

Data Sources: Searches of multiple electronic databases, without language restrictions, from inception to 6 January 2020, and reference lists of selected articles.

Study Selection: Observational studies of adults with opioid prescriptions for outpatient acute musculoskeletal injuries, in an adjusted model, that explored risk factors for prolonged use.

Data Extraction: 6 reviewers, working in pairs, independently extracted data, rated the quality of studies, and evaluated the certainty of evidence.

Data Synthesis: 14 cohorts with 13 263 393 participants were included. The overall prevalence of prolonged opioid use after musculoskeletal injury for high-risk populations (that is, patients receiving workers' compensation benefits, Veterans Affairs claimants, or patients with high rates of concurrent substance use disorder) was 27% (95% CI, 18% to 37%). The prevalence among low-risk populations was 6% (CI, 4% to 8%; for interaction < 0.001). Moderate-certainty evidence showed increased odds of persistent opioid use with older age (absolute risk increase [ARI] for every 10-year increase, 1.1% [CI, 0.7% to 1.5%]) and physical comorbidity (ARI, 0.9% [CI, 0.1% to 1.7%]). Low-certainty evidence suggested increased risk for persistent opioid use with past or current substance use disorder (ARI, 10.5% [CI, 4.2% to 19.8%]), prescriptions lasting more than 7 days (median ARI, 4.5%), and higher morphine milligram equivalents per day.

Limitation: Sparse, heterogeneous data with suboptimal adjustment for potential confounders.

Conclusion: Avoiding prescribing opioids for acute musculoskeletal injuries to patients with past or current substance use disorder, and restricting duration to 7 days or less and using lower doses when they are prescribed, are potentially important targets to reduce rates of persistent opioid use.

Primary Funding Source: National Safety Council. (PROSPERO: CRD42018104968).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7326/M19-3600DOI Listing
November 2020

Prognostic models for newly-diagnosed chronic lymphocytic leukaemia in adults: a systematic review and meta-analysis.

Cochrane Database Syst Rev 2020 07 31;7:CD012022. Epub 2020 Jul 31.

Cochrane Cancer, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.

Background: Chronic lymphocytic leukaemia (CLL) is the most common cancer of the lymphatic system in Western countries. Several clinical and biological factors for CLL have been identified. However, it remains unclear which of the available prognostic models combining those factors can be used in clinical practice to predict long-term outcome in people newly-diagnosed with CLL.

Objectives: To identify, describe and appraise all prognostic models developed to predict overall survival (OS), progression-free survival (PFS) or treatment-free survival (TFS) in newly-diagnosed (previously untreated) adults with CLL, and meta-analyse their predictive performances.

Search Methods: We searched MEDLINE (from January 1950 to June 2019 via Ovid), Embase (from 1974 to June 2019) and registries of ongoing trials (to 5 March 2020) for development and validation studies of prognostic models for untreated adults with CLL. In addition, we screened the reference lists and citation indices of included studies.

Selection Criteria: We included all prognostic models developed for CLL which predict OS, PFS, or TFS, provided they combined prognostic factors known before treatment initiation, and any studies that tested the performance of these models in individuals other than the ones included in model development (i.e. 'external model validation studies'). We included studies of adults with confirmed B-cell CLL who had not received treatment prior to the start of the study. We did not restrict the search based on study design.

Data Collection And Analysis: We developed a data extraction form to collect information based on the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS). Independent pairs of review authors screened references, extracted data and assessed risk of bias according to the Prediction model Risk Of Bias ASsessment Tool (PROBAST). For models that were externally validated at least three times, we aimed to perform a quantitative meta-analysis of their predictive performance, notably their calibration (proportion of people predicted to experience the outcome who do so) and discrimination (ability to differentiate between people with and without the event) using a random-effects model. When a model categorised individuals into risk categories, we pooled outcome frequencies per risk group (low, intermediate, high and very high). We did not apply GRADE as guidance is not yet available for reviews of prognostic models.

Main Results: From 52 eligible studies, we identified 12 externally validated models: six were developed for OS, one for PFS and five for TFS. In general, reporting of the studies was poor, especially predictive performance measures for calibration and discrimination; but also basic information, such as eligibility criteria and the recruitment period of participants was often missing. We rated almost all studies at high or unclear risk of bias according to PROBAST. Overall, the applicability of the models and their validation studies was low or unclear; the most common reasons were inappropriate handling of missing data and serious reporting deficiencies concerning eligibility criteria, recruitment period, observation time and prediction performance measures. We report the results for three models predicting OS, which had available data from more than three external validation studies: CLL International Prognostic Index (CLL-IPI) This score includes five prognostic factors: age, clinical stage, IgHV mutational status, B2-microglobulin and TP53 status. Calibration: for the low-, intermediate- and high-risk groups, the pooled five-year survival per risk group from validation studies corresponded to the frequencies observed in the model development study. In the very high-risk group, predicted survival from CLL-IPI was lower than observed from external validation studies. Discrimination: the pooled c-statistic of seven external validation studies (3307 participants, 917 events) was 0.72 (95% confidence interval (CI) 0.67 to 0.77). The 95% prediction interval (PI) of this model for the c-statistic, which describes the expected interval for the model's discriminative ability in a new external validation study, ranged from 0.59 to 0.83. Barcelona-Brno score Aimed at simplifying the CLL-IPI, this score includes three prognostic factors: IgHV mutational status, del(17p) and del(11q). Calibration: for the low- and intermediate-risk group, the pooled survival per risk group corresponded to the frequencies observed in the model development study, although the score seems to overestimate survival for the high-risk group. Discrimination: the pooled c-statistic of four external validation studies (1755 participants, 416 events) was 0.64 (95% CI 0.60 to 0.67); 95% PI 0.59 to 0.68. MDACC 2007 index score The authors presented two versions of this model including six prognostic factors to predict OS: age, B2-microglobulin, absolute lymphocyte count, gender, clinical stage and number of nodal groups. Only one validation study was available for the more comprehensive version of the model, a formula with a nomogram, while seven studies (5127 participants, 994 events) validated the simplified version of the model, the index score. Calibration: for the low- and intermediate-risk groups, the pooled survival per risk group corresponded to the frequencies observed in the model development study, although the score seems to overestimate survival for the high-risk group. Discrimination: the pooled c-statistic of the seven external validation studies for the index score was 0.65 (95% CI 0.60 to 0.70); 95% PI 0.51 to 0.77.

Authors' Conclusions: Despite the large number of published studies of prognostic models for OS, PFS or TFS for newly-diagnosed, untreated adults with CLL, only a minority of these (N = 12) have been externally validated for their respective primary outcome. Three models have undergone sufficient external validation to enable meta-analysis of the model's ability to predict survival outcomes. Lack of reporting prevented us from summarising calibration as recommended. Of the three models, the CLL-IPI shows the best discrimination, despite overestimation. However, performance of the models may change for individuals with CLL who receive improved treatment options, as the models included in this review were tested mostly on retrospective cohorts receiving a traditional treatment regimen. In conclusion, this review shows a clear need to improve the conducting and reporting of both prognostic model development and external validation studies. For prognostic models to be used as tools in clinical practice, the development of the models (and their subsequent validation studies) should adapt to include the latest therapy options to accurately predict performance. Adaptations should be timely.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/14651858.CD012022.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078230PMC
July 2020

Drug treatments for covid-19: living systematic review and network meta-analysis.

BMJ 2020 07 30;370:m2980. Epub 2020 Jul 30.

Department of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main St W, Hamilton, ON L8S 4L8, Canada.

Objective: To compare the effects of treatments for coronavirus disease 2019 (covid-19).

Design: Living systematic review and network meta-analysis.

Data Sources: WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, up to 1 March 2021 and six additional Chinese databases up to 20 February 2021. Studies identified as of 12 February 2021 were included in the analysis.

Study Selection: Randomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles.

Methods: After duplicate data abstraction, a bayesian network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development, and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance.

Results: 196 trials enrolling 76 767 patients were included; 111 (56.6%) trials and 35 098 (45.72%) patients are new from the previous iteration; 113 (57.7%) trials evaluating treatments with at least 100 patients or 20 events met the threshold for inclusion in the analyses. Compared with standard care, corticosteroids probably reduce death (risk difference 20 fewer per 1000 patients, 95% credible interval 36 fewer to 3 fewer, moderate certainty), mechanical ventilation (25 fewer per 1000, 44 fewer to 1 fewer, moderate certainty), and increase the number of days free from mechanical ventilation (2.6 more, 0.3 more to 5.0 more, moderate certainty). Interleukin-6 inhibitors probably reduce mechanical ventilation (30 fewer per 1000, 46 fewer to 10 fewer, moderate certainty) and may reduce length of hospital stay (4.3 days fewer, 8.1 fewer to 0.5 fewer, low certainty), but whether or not they reduce mortality is uncertain (15 fewer per 1000, 30 fewer to 6 more, low certainty). Janus kinase inhibitors may reduce mortality (50 fewer per 1000, 84 fewer to no difference, low certainty), mechanical ventilation (46 fewer per 1000, 74 fewer to 5 fewer, low certainty), and duration of mechanical ventilation (3.8 days fewer, 7.5 fewer to 0.1 fewer, moderate certainty). The impact of remdesivir on mortality and most other outcomes is uncertain. The effects of ivermectin were rated as very low certainty for all critical outcomes, including mortality. In patients with non-severe disease, colchicine may reduce mortality (78 fewer per 1000, 110 fewer to 9 fewer, low certainty) and mechanical ventilation (57 fewer per 1000, 90 fewer to 3 more, low certainty). Azithromycin, hydroxychloroquine, lopinavir-ritonavir, and interferon-beta do not appear to reduce risk of death or have an effect on any other patient-important outcome. The certainty in effects for all other interventions was low or very low.

Conclusion: Corticosteroids and interleukin-6 inhibitors probably confer important benefits in patients with severe covid-19. Janus kinase inhibitors appear to have promising benefits, but certainty is low. Azithromycin, hydroxychloroquine, lopinavir-ritonavir, and interferon-beta do not appear to have any important benefits. Whether or not remdesivir, ivermectin, and other drugs confer any patient-important benefit remains uncertain.

Systematic Review Registration: This review was not registered. The protocol is publicly available in the supplementary material.

Readers' Note: This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This is the fourth version of the original article published on 30 July 2020 (BMJ 2020;370:m2980), and previous versions can be found as data supplements. When citing this paper please consider adding the version number and date of access for clarity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmj.m2980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7390912PMC
July 2020

Management of Acute Decompensated Heart Failure in the Cardiac Intensive Care Unit: The Importance of Co-management With a Heart Failure Specialist.

CJC Open 2020 Jul 4;2(4):229-235. Epub 2020 Mar 4.

Peter Munk Cardiac Centre, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.

Background: Heart failure (HF) is a common reason for admission to the cardiac intensive care unit. We sought to identify the role of an HF consultation service in improving the management of this patient population.

Methods: We identified all adult patients admitted to the cardiac intensive care unit (2014-2015) at the University Health Network with a diagnosis of acute decompensated HF ± cardiogenic shock (CS). Clinical characteristics and course were recorded. We calculated a propensity score-adjusted association between HF consultation and in-hospital mortality.

Results: A total of 285 unique patients were identified in our cohort. Of these, 82 (28.7%) died. A total of 150 patients (52.6%) were co-managed by an HF service, and 135 patients (47.3%) were not. Patients who were managed by an HF team were younger (52.5 vs 68.0 years, 0.0001), were more likely to be admitted with CS (61.3 vs 41.5%, 0.0009), and had higher rates of vasoactive medications during their admission (69.3% vs 52.6%, 0.005). At discharge, there were higher rates of discharge to a HF clinic (52.0% vs 27.5%, 0.0001) and prescription of guideline-directed medical therapy. In-hospital mortality was lower in those co-managed by a HF team (16.7% vs 42.2%, 0.0001). HF consultation reduced the odds of readmission by 76% (odds ratio, 0.24; 95% confidence interval, 0.13-0.47).

Conclusions: Patients managed by a HF team were more likely to be in CS at admission, to survive to discharge from hospital, and to be initiated on guideline-directed medical therapy with HF follow-up.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cjco.2020.02.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365826PMC
July 2020

Evaluating the credibility of anchor based estimates of minimal important differences for patient reported outcomes: instrument development and reliability study.

BMJ 2020 06 4;369:m1714. Epub 2020 Jun 4.

Department of Health Research Methods, Evidence and Impact, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4L8, Canada.

Objective: To develop an instrument to evaluate the credibility of anchor based minimal important differences (MIDs) for outcome measures reported by patients, and to assess the reliability of the instrument.

Design: Instrument development and reliability study.

Data Sources: Initial criteria were developed for evaluating the credibility of anchor based MIDs based on a literature review (Medline, Embase, CINAHL, and PsycInfo databases) and the experience of the authors in the methodology for estimation of MIDs. Iterative discussions by the team and pilot testing with experts and potential users facilitated the development of the final instrument.

Participants: With the newly developed instrument, pairs of masters, doctoral, or postdoctoral students with a background in health research methodology independently evaluated the credibility of a sample of MID estimates.

Main Outcome Measures: Core credibility criteria applicable to all anchor types, additional criteria for transition rating anchors, and inter-rater reliability coefficients were determined.

Results: The credibility instrument has five core criteria: the anchor is rated by the patient; the anchor is interpretable and relevant to the patient; the MID estimate is precise; the correlation between the anchor and the outcome measure reported by the patient is satisfactory; and the authors select a threshold on the anchor that reflects a small but important difference. The additional criteria for transition rating anchors are: the time elapsed between baseline and follow-up measurement for estimation of the MID is optimal; and the correlations of the transition rating with the baseline, follow-up, and change score in the patient reported outcome measures are satisfactory. Inter-rater reliability coefficients (ĸ) for the core criteria and for one item from the additional criteria ranged from 0.70 to 0.94. Reporting issues prevented the evaluation of the reliability of the three other additional criteria for the transition rating anchors.

Conclusions: Researchers, clinicians, and healthcare policy decision makers can consider using this instrument to evaluate the design, conduct, and analysis of studies estimating anchor based minimal important differences.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmj.m1714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270853PMC
June 2020

Prognostic Value of Late Gadolinium Enhancement for the Prediction of Cardiovascular Outcomes in Dilated Cardiomyopathy: An International, Multi-Institutional Study of the MINICOR Group.

Circ Cardiovasc Imaging 2020 04 21;13(4):e010105. Epub 2020 Apr 21.

Departments of Cardiac Sciences and Diagnostic Imaging, Libin Cardiovascular Institute of Alberta, Calgary, Canada (S.D., J.F., J.A.W.).

Background: Dilated cardiomyopathy is associated with increased risk of major cardiovascular events. Late gadolinium enhancement (LGE) cardiac magnetic resonance imaging is a unique tissue-based marker that, in single-center studies, suggests strong prognostic value. We retrospectively studied associations between LGE presence and adverse cardiovascular events in patients with dilated cardiomyopathy in a multicenter setting as part of an emerging global consortium (MINICOR [Multi-Modal International Cardiovascular Outcomes Registry]).

Methods: Consecutive patients with dilated cardiomyopathy referred for cardiac magnetic resonance (2000-2017) at 12 institutions in 4 countries were studied. Using multivariable Cox proportional hazard and semiparametric Fine and Gray models, we evaluated the association between LGE and the composite primary end point of all-cause mortality, heart transplantation, or left ventricular assist device implant and a secondary arrhythmic end point of sudden cardiac death or appropriate implantable cardioverter-defibrillator shock.

Results: We studied 1672 patients, mean age 56±14 years (29% female), left ventricular ejection fraction 33±11%, and 25% having New York Heart Association class III to IV; 650 patients (39%) had LGE. During 2.3 years (interquartile range, 1.0-4.3) follow-up, 160 patients experienced the primary end point, and 88 experienced the arrhythmic end point. In multivariable analyses, LGE was associated with 1.5-fold (hazard ratio, 1.45 [95% CI, 1.03-2.04]) risk of the primary end point and 1.8-fold (hazard ratio, 1.82 [95% CI, 1.20-3.06]) risk of the arrhythmic end point. Primary end point risk was increased in patients with multiple LGE patterns, although arrhythmic risk was higher among patients receiving primary prevention implantable cardioverter-defibrillator and widening QRS.

Conclusions: In this large multinational study of patients with dilated cardiomyopathy, the presence of LGE showed strong prognostic value for identification of high-risk patients. Randomized controlled trials evaluating LGE-based care management strategies are warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCIMAGING.119.010105DOI Listing
April 2020

Letter to the editor: Increased sensitivity to ischemic interval of donor hearts with diminished left ventricular function.

J Heart Lung Transplant 2020 Mar 29. Epub 2020 Mar 29.

Peter Munk Cardiac Centre, University Health Network, Ted Rogers Centre for Heart Research, Toronto, Ontario, Canada. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.healun.2020.03.014DOI Listing
March 2020

Late Onset Invasive Pulmonary Aspergillosis in Lung Transplant Recipients in the Setting of a Targeted Prophylaxis/Preemptive Antifungal Therapy Strategy.

Transplantation 2020 12;104(12):2575-2581

Multi-Organ Transplant Program, Division of Infectious Diseases, University Health Network, University of Toronto, Toronto, ON, Canada.

Background: Invasive pulmonary aspergillosis (IPA) is a significant cause of morbidity and mortality in lung transplant recipients (LTRs). It is unclear how a targeted prophylaxis/ preemptive antifungal therapy strategy impacts the incidence of IPA beyond the first-year posttransplant.

Methods: This is a retrospective cohort of LTRs from January 2010 to December 2014. We included all LTRs who survived beyond the first year and followed them until death or 4 years postoperatively. Incidence of probable/proven IPA and Aspergillus colonization were assessed as per International Society for Heart and Lung Transplantation (ISHLT) criteria. Patients with risk factors, positive Aspergillus cultures, or galactomannan (GM) received targeted prophylaxis/preemptive therapy within the first-year posttransplant.

Results: During the study period, 350 consecutive LTRs underwent 1078 bronchoscopies. Positive bronchoalveolar lavage for GM or Aspergillus cultures was reported for 15% (52/350) of LTRs between 2 and 4 years after transplantation. Among them, the median time to positive Aspergillus culture or GM positivity was 703 days (interquartile range, 529-754 d). The incidence rate of IPA and Aspergillus colonization was 30 of 1000 patient-y, and 63 of 1000 patient-y, respectively. The mortality rate was significantly higher in patients with IPA than without IPA (107/1000 patient-years versus 18/1000 patient-years; P < 0.0001). Rate of first-year colonization and IPA was 33% and 9%, respectively. Among the 201 patients who had a negative bronchoscopy during the first year posttransplant, only 6 (3%) developed IPA during the follow-up.

Conclusions: A targeted prophylaxis/preemptive therapy strategy within the first-year posttransplant resulted in 4% incidence of IPA at 4-years after transplantation. However, IPA was associated with higher mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TP.0000000000003187DOI Listing
December 2020

Utility of the INTERMACS profile at the time of assessment for heart transplant.

Clin Transplant 2020 03 17;34(3):e13796. Epub 2020 Feb 17.

Ted Rogers Centre for Heart Research, Multi-Organ Transplant Program, Toronto General Hospital, University Health Network, Toronto, ON, Canada.

The Interagency Registry of Mechanically Assisted Circulatory Support (INTERMACS) profiles are associated with mortality in heart failure patients undergoing ventricular assist device (VAD) implantation and heart transplantation (HTx). We assessed the prognostic value of the INTERMACS profile at the time of assessment for HTx or durable VAD implantation as bridge to candidacy (BTC). A total of 503 consecutive patients considered for HTx or VAD between 2006 and 2016 were included. The associations between INTERMACS profile and (a) waitlist mortality or delisting, (b) probability of HTx, and (c) overall mortality or delisting were evaluated using multivariable analysis. Median follow-up time was 2.9 years (IQR: 0.9-5.5) during which 184 received VAD, 347 received HTx, and 73 died (27 waitlist, 46 post-transplant). INTERMACS I-II profile was associated with higher waitlist mortality or delisting (HR: 3.83, 95% CI: 1.22-12.03), and this risk was reversed by VAD implantation (HR: 0.12, 95% CI: 0.03-0.50). INTERMACS III-IV profile was associated with a higher probability of HTx (HR: 1.82, 95% CI: 1.37-2.40). INTERMACS profile was not associated with the composite outcome of overall mortality or delisting. These results emphasize the prognostic utility of INTERMACS at time of decision for advanced therapies and its potential value in selecting patients for different interventions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ctr.13796DOI Listing
March 2020

GRADE Guidelines 28: Use of GRADE for the assessment of evidence about prognostic factors: rating certainty in identification of groups of patients with different absolute risks.

J Clin Epidemiol 2020 05 23;121:62-70. Epub 2020 Jan 23.

Department of Health Research Methods, Evidence, and Impact, McMaster University, Ontario, Canada.

Objective: The objective of this study was to provide guidance on the use of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to determine certainty in estimates of association between prognostic factors and future outcomes.

Study Design And Setting: We developed our guidance through an iterative process that involved review of published systematic reviews and meta-analyses of prognostic factors, consultation with members, feedback, presentation, and discussion at the GRADE Working Group meetings.

Results: For questions of prognosis, a body of observational evidence (potentially including patients enrolled in randomized controlled trials) begins as high certainty in the evidence. The five domains of GRADE for rating down certainty in the evidence, that is, risk of bias, imprecision, inconsistency, indirectness, and publication bias, as well as the domains for rating up, also apply to estimates of associations between prognostic factors and outcomes. One should determine if their ratings do not consider (noncontextualized) or consider (contextualized) the clinical context as this will may result in variable judgments on certainty of the evidence.

Conclusions: The same principles GRADE proposed for bodies of evidence addressing treatment and overall prognosis work well in assessing individual prognostic factors, both in noncontextualized and contextualized settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jclinepi.2019.12.023DOI Listing
May 2020
-->