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Immune thrombocytopenia (ITP) is a diagnosis of exclusion that can resemble other thrombocytopenic disorders.To develop a clinical prediction model (CPM) for the diagnosis of ITP to aid hematogists in investigating patients presenting with undifferentiated thrombocytopenia.We designed a CPM for ITP diagnosis at the time of the initial hematology consultation using penalized logistic regression based on data from patients with thrombocytopenia enrolled in the McMaster ITP registry (n = 523) called the Predict-ITP Tool. The case definition for ITP was a platelet count less than 100 × 10The final model included the following variables: (1) platelet count variability (based on three or more platelet count values), (2) lowest platelet count value, (3) maximum mean platelet volume, and (4) history of major bleeding (defined by the ITP bleeding scale). The optimism-corrected c-statistic was 0.83, the calibration slope was 0.88, and calibration-in-the-large for all performance measures was0.001 with standard error0.001, indicating good discrimination and excellent calibration.The Predict-ITP Tool can estimate the likelihood of ITP for a given patient with thrombocytopenia at the time of the initial hematology consultation. The tool had high predictive accuracy for the diagnosis of ITP.

To evaluate reporting of minimal important difference (MID) estimates using anchor-based methods for patient-reported outcome measures (PROMs), and the association with reporting deficiencies on their credibility.Systematic survey of primary studies empirically estimating MIDs. We searched Medline, EMBASE, PsycINFO, and the Patient-Reported Outcome and Quality of Life Instruments Database until October 2018. We evaluated study reporting, focusing on participants' demographics, intervention(s), characteristics of PROMs and anchors, and MID estimation method(s). We assessed the impact of reporting issues on credibility of MID estimates.In 585 studies reporting on 5,324 MID estimates for 526 distinct PROMs, authors frequently failed to adequately report key characteristics of PROMs and MIDs, including minimum and maximum values of PROM scale, measure of variability accompanying the MID estimate and number of participants included in the MID calculation. Across MID estimates (n = 5,324), the most serious reporting issues impacting credibility included infrequent reporting of the correlation between the anchor and PROM (66%), inadequate details to judge precision of MID point estimate (13%), and insufficient information about the threshold used to ascertain MIDs (16%).Serious issues of incomplete reporting in the MID literature threaten the optimal use of MID estimates to inform the magnitude of effects of interventions on PROMs.

Study Design Systematic Review Objectives To conduct a meta-analysis on the survivorship of commonly performed cervical spine procedures to develop survival function curves for (i) second surgery at any cervical level, and (ii) adjacent level surgery. Methods A systematic review of was conducted following PRISMA guidelines. Articles with cohorts of greater than 20 patients followed for a minimum of 36 months and with available survival data were included. Procedures included were anterior cervical discectomy and fusion (ACDF), cervical disc arthroplasty (ADR), laminoplasty (LAMP), and posterior laminectomy and fusion (PDIF). Reconstructed individual patient data were pooled across studies using parametric Bayesian survival meta-regression. Results Of 1829 initial titles, 16 citations were included for analysis. 73 811 patients were included in the second surgery analysis and 2858 patients in the adjacent level surgery analysis. We fit a Log normal accelerated failure time model to the second surgery data and a Gompertz proportional hazards model to the adjacent level surgery data. Relative to ACDF, the risk of second surgery was higher with ADR and PDIF with acceleration factors 1.73 (95% CrI: 1.04, 2.80) and 1.35 (95% CrI: 1.25, 1.46) respectively. Relative to ACDF, the risk of second surgery was lower with LAMP with deceleration factor .06 (95% CrI: .05, .07). ADR decreased the risk of adjacent level surgery with hazard ratio .43 (95% CrI: .33, .55). Conclusions In cases of clinical equipoise between fusion procedures, our analysis suggests superior survivorship with anterior procedures. For all procedures, laminoplasty demonstrated superior survivorship.

Anticoagulation requires urgent reversal in cases of life-threatening bleeding or invasive procedures.Network meta-analysis for comparing the safety and efficacy of warfarin reversal strategies including plasma and prothrombin complex concentrates (PCCs).Seven studies including 594 subjects using reversal agents plasma, 3-factor-PCC (Uman Complex and Konyne), and 4-factor-PCC (Beriplex/KCentra, Octaplex, and Cofact) met inclusion criteria. Compared with plasma, patients receiving Cofact probably have a higher rate of international normalized ratio (INR) correction (risk difference [RD] 499 more per 1000 patients, 95% confidence interval [CI], 176-761, low certainty[LC]); higher reversal of bleeding (323 more per 1000 patients, 11-344 more, LC); and fewer transfusion requirements (0.96 fewer units, 1.65-0.27 fewer, LC). Patients receiving Beriplex/KCentra probably have a higher rate of INR correction (476 more per 1000 patients, 332-609 more, LC); higher reversal of bleeding (127 more per 1000 patients, 43 fewer to 236 more); and similar transfusion requirements (0.01 fewer units, 0.31 fewer to 0.28 more, high/moderate certainty). Patients receiving Octaplex probably have a higher rate of INR correction (RD 579 more per 1000 patients, 189-825 more, LC).PCCs probably provide an advantage in INR reversal compared to plasma. There was no added risk of adverse events with PCCs.

Prognostic factors in lung transplantation are those variables that are associated with transplant outcomes. Knowledge of donor and recipient prognostic variables can aid in the optimal allocation of donor lungs to transplant recipients and can also inform post-operative discussions with patients about prognosis. Current research findings related to prognostic factors in lung transplantation are inconsistent and the relative importance of various factors is unclear. This review aims to provide the best possible estimates of the association between putative prognostic variables and 1-year all-cause mortality in adult lung transplant recipients.We searched 5 bibliographic databases for studies assessing the associations between putative predictors (related to lung donors, recipients, or the transplant procedure) and 1-year recipient mortality. We pooled data across studies when justified and utilized GRADE methodology to assess the certainty in the evidence.From 72 eligible studies (2002-2020), there were 34 recipient variables, 4 donor variables, 10 procedural variables, and 7 post-transplant complication variables that were amenable to a meta-analysis. With a high degree of certainty in the evidence only post-transplant need for extra-corporeal membrane oxygenation (ECMO) (HR 1.91, 95% CI 1.79-2.04) predicted 1-year mortality. No donor variables appeared to predict transplant outcome with high or even moderate certainty.Across the range of contemporary donors and recipients that clinicians accept for lung transplantation, this review, with high certainty, found 1 prognostic factor that predicted 1-year mortality, and 37 additional factors with a moderate degree of certainty. The lack of prognostic significance for some widely accepted factors (e.g., donor smoking, age) likely relates to existing limits in the range of these variables at the time of donor and recipient selection.

Network meta-analysis (NMA) is an increasingly popular statistical method of synthesising evidence to assess the comparative benefits and harms of multiple treatments in a single analysis. Several automated software packages facilitate conducting NMA using either of two alternative approaches, Bayesian or frequentist frameworks. Researchers must choose a framework for conducting NMA (Bayesian or frequentist) and select appropriate model(s), and those conducting NMA need to understand the assumptions and limitations of different approaches. Bayesian models are more frequently used and can be more flexible but require checking additional assumptions and greater statistical expertise that are often ignored. The present paper describes the important theoretical aspects of Bayesian and frequentist models for NMA and the applications and considerations of contrast-synthesis and arm-synthesis NMAs. In addition, we present evidence from a limited number of simulation and empirical studies that compared different frequentist and Bayesian models and provide an overview of available automated software packages to perform NMA. We will conclude that when analysts choose appropriate models, there are seldom important differences in the results of Bayesian and frequentist approaches and that network meta-analysts should therefore focus on model features rather than the statistical framework.

Background : Invasive fungal infection (IFI) remains a common complication after lung transplantation, causing significant morbidity and mortality. We have attempted to quantify systematically risk factors of IFI in lung transplant recipients. Methods : Studies were retrieved from Ovid MEDLINE, Ovid Embase, Cochrane database of systematic reviews and Cochrane central register of controlled trials. All case-control and cohort studies evaluating the risk factors of IFI in adult lung transplant recipients were screened. Two researchers reviewed and assessed all studies independently. We pooled the estimated effect of each factor associated with IFI by using a random effect model. Results : Eight studies were included in the systematic review and five studies were eligible for the meta-analysis. Rates of IFI range from 8-33% in lung transplant recipients. Independent risk factors for invasive aspergillosis (IA) in lung transplantation include previous fungal colonization (OR 2.44; 95% CI 0.08-0.47), cytomegalovirus infection (OR 1.96; 95% CI 1.08-3.56) and single lung transplantation (OR 1.77; 95% CI 1.08-2.91). Pre-emptive antifungal therapy (OR 0.20; 95% CI 0.09-0.48) is a protective factor for IA in lung transplant (OR 0.2; 95% CI 0.08-0.47). Conclusion : Cytomegalovirus infection, previous fungal colonization and single lung transplantation independently increase the risk of IA in lung transplant recipients. Pre-emptive antifungal therapy is a protective factor for IA in the lung transplant population.

The benefit associated with the incorporation of vincristine-corticosteroid pulses into maintenance therapy for pediatric acute lymphoblastic leukemia (ALL) is unclear, particularly in the context of modern intensive therapy. This systematic review and meta-analysis examined the impact of reducing frequency of vincristine-steroid pulses during maintenance for newly diagnosed pediatric patients with B-cell ALL. Two authors reviewed all eligible studies identified through a comprehensive search, extracted data from the 25 included publications (12 513 patients), and assessed risk of bias. We created historical and contemporary subgroups; the latter included trials providing a version of Protocol III from early Berlin-Frankfurt-Munster trials and eliminating routine prophylactic cranial radiation. Meta-analysis of event-free survival data suggested no benefit between more frequent or less frequent pulses in contemporary trials (HR 0.96, 95%CI 0.85-1.09) which differs significantly from historical trials (HR 0.79, 95%CI 0.68-0.91, p=0.04). We found no significant impact of reduced pulse frequency on overall survival or relapse risk. There was however an increased odds of Grade 3+ non-hepatic toxicity in the high pulse frequency group (OR 1.31, 95%CI 1.12-1.52). This systematic review suggests that the previous benefit conferred by frequent pulses of vincristine-steroids in maintenance therapy for pediatric B-cell ALL in historical trials no longer applies in contemporary trials but is associated with toxicity. These results will help guide development of the next phase of clinical trials in the field of pediatric ALL and question the continued use of pulses in maintenance for patients not on clinical trials, particularly those experiencing toxicity.

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 centers, 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-center, 23 (25.3%) enrolled

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

Fulminant myocarditis (FM) may lead to cardiogenic shock requiring veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Results of effectiveness studies of VA-ECMO have been contradictory. We evaluated the aggregate short-term mortality after VA-ECMO and predictive factors in patients with FM. We systematically searched in electronic databases (February 2022) to identify studies evaluating short-term mortality (defined as mortality at 30 days or in-hospital) after VA-ECMO support for FM. We included studies with 5 or more patients published after 2009. We assessed the quality of the evidence using the QUIPS and GRADE tools. Mortality was pooled using random effect models. We performed meta-regression to explore heterogeneity based on a priori defined factors. We included 54 observational studies encompassing 2388 FM patients supported with VA-ECMO. Median age was 41 years (25th to 75th percentile 37-47), and 50% were female. The pooled short-term mortality was 35% (95% CI 29-40%, I

DescriptionCoronavirus disease 2019 convalescent plasma (CCP) has emerged as a potential treatment of COVID-19. However, meta-analysis data and recommendations are limited. The Association for the Advancement of Blood and Biotherapies (AABB) developed clinical practice guidelines for the appropriate use of CCP.MethodsThese guidelines are based on 2 living systematic reviews of randomized controlled trials (RCTs) evaluating CCP from 1 January 2019 to 26 January 2022. There were 33 RCTs assessing 21916 participants. The results were summarized using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method. An expert panel reviewed the data using the GRADE framework to formulate recommendations.Recommendation 1 (outpatient)The AABB suggests CCP transfusion in addition to the usual standard of care for outpatients with COVID-19 who are at high risk for disease progression (weak recommendation, moderate-certainty evidence).Recommendation 2 (inpatient)The AABB recommends against CCP transfusion for unselected hospitalized persons with moderate or severe disease (strong recommendation, high-certainty evidence). This recommendation does not apply to immunosuppressed patients or those who lack antibodies against SARS-CoV-2.Recommendation 3 (inpatient)The AABB suggests CCP transfusion in addition to the usual standard of care for hospitalized patients with COVID-19 who do not have SARS-CoV-2 antibodies detected at admission (weak recommendation, low-certainty evidence).Recommendation 4 (inpatient)The AABB suggests CCP transfusion in addition to the usual standard of care for hospitalized patients with COVID-19 and preexisting immunosuppression (weak recommendation, low-certainty evidence).Recommendation 5 (prophylaxis)The AABB suggests against prophylactic CCP transfusion for uninfected persons with close contact exposure to a person with COVID-19 (weak recommendation, low-certainty evidence).Good clinical practice statementCCP is most effective when transfused with high neutralizing titers to infected patients early after symptom onset.

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.

Purpose Primary graft dysfunction (PGD) is a life-threatening complication and a leading cause of early mortality post heart transplant (HTx). Recent studies evaluating the incidence and prognosis of PGD have benefited from the ISHLT 2014 Consensus Report which clearly defines this condition. Our objective was to systematically review all studies that reported the incidence of PGD in adult HTX recipients since 2014 to more accurately identify its incidence and impact on mortality. Methods We conducted a systematic search of the literature in Medline in October 2019. We included studies that reported the incidence of PGD in adult HTx recipients, based on the 2014 ISHLT Consensus Report. Two independent reviewers screened citations and performed data abstraction. We used a random effects meta-analysis to pool the incidence among HTx recipients, as well as the rate of mortality among those who developed PGD. We applied the GRADE instrument for incidence and mortality separately to determine our certainty in the pooled estimates. Results Of 127 publications screened, we included 36 observational studies. HTx recipient age ranged from 24-69 years and 24% were female. Donor age ranged from 23-50 years, sex mismatch occurred in 21% and ischemic time ranged from 86-273 minutes. We observed similar incidence for each severity of PGD but increasing risk of 1-year mortality (Table 1). Estimates of 30-day mortality were only available for severe PGD: 39% (95% CI 32% - 46%, 9 studies, high certainty). Conclusion Based on the 2014 ISHLT criteria, the published pooled incidence of PGD is low, and its prognosis is poor. The extensive heterogeneity in incidence and mortality suggests inconsistencies in the recognition and/or management of PGD. This represents an opportunity for improved risk stratification, prevention and management strategies.

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. We meta-analyzed mortality after VA-ECMO for CS complicating AMI and the effect of factors from systematically selected studies published after 2009. 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. These results provide clinicians with a framework for selecting patients for VA-ECMO for CS complicating AMI.

Predicted heart mass (PHM) was neither derived nor evaluated in an obese population. Our objective was to evaluate size mismatch using actual body weight or ideal body weight (IBW)-adjusted PHM on mortality and risk assessment.We conducted a retrospective cohort study of adult recipients with BMI ≥30 kg/m10,817 HT recipients, age 55 (IQR 46-62) years, 23% female, BMI 31 kg/mActual PHM can be used for size matching when assessing mortality risk in obese recipients or recipients of obese donors. There is no advantage to re-calculating PHM using IBW to define candidate risk at the time of organ allocation.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a prevailing option for the management of severe early graft dysfunction. This systematic review and individual patient data (IPD) meta-analysis aims to evaluate (1) mortality, (2) rates of major complications, (3) prognostic factors, and (4) the effect of different VA-ECMO strategies on outcomes in adult heart transplant (HT) recipients supported with VA-ECMO.We conducted a systematic search and included studies of adults (≥18 years) who received VA-ECMO during their index hospitalization after HT and reported on mortality at any timepoint. We pooled data using random effects models. To identify prognostic factors, we analysed IPD using mixed effects logistic regression. We assessed the certainty in the evidence using the GRADE framework. We included 49 observational studies of 1477 patients who received VA-ECMO after HT, of which 15 studies provided IPD for 448 patients. There were no differences in mortality estimates between IPD and non-IPD studies. The short-term (30-day/in-hospital) mortality estimate was 33% (moderate certainty, 95% confidence interval [CI] 28%-39%) and 1-year mortality estimate 50% (moderate certainty, 95% CI 43%-57%). Recipient age (odds ratio 1.02, 95% CI 1.01-1.04) and prior sternotomy (OR 1.57, 95% CI 0.99-2.49) are associated with increased short-term mortality. There is low certainty evidence that early intraoperative cannulation and peripheral cannulation reduce the risk of short-term death.One-third of patients who receive VA-ECMO for early graft dysfunction do not survive 30 days or to hospital discharge, and one-half do not survive to 1 year after HT. Improving outcomes will require ongoing research focused on optimizing VA-ECMO strategies and care in the first year after HT.

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.

ObjectiveTo 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.MethodsWe 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.ResultsOf 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.ConclusionOf 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 numberCRD42020168351.

ObjectiveTo 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.MethodsWe 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.ResultsOf 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).ConclusionIn 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.

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, I2 = 87.13%, moderate certainty), all-cause hospitalization events (HR 0.91, 95%CI 0.88–0.93, I2 = 44.4%, high certainty) and their composite endpoint (HR 0.93 per 10 mmHg, 95%CI 0.91–0.94, I2 = 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.

Background Statins are competitive inhibitors of 3-hydroxy-3methylglutaryl coenzyme A reductase (HMG-CoA reductase) that catalyses HMG-CoA conversion to mevalonate, a process involved in synthesizing cholesterol in humans and ergosterol in fungi. The effect of statin use on the risk of development of invasive aspergillosis (IA) in lung transplant recipients (LTRs) is not well documented. Methods This retrospective study included LTRs from 2010 to 2017 who were followed for one-year post-transplant. Proven or probable IA was diagnosed as per ISHLT criteria. We performed a multivariable Cox proportional hazards model of the association between IA and statin use (minimum of 2 weeks duration prior to IA), adjusting for other known IA risk factors. Results We identified 785 LTRs, 44% female, mean age 53 years old, the most common underlying disease being pulmonary fibrosis (23.8%). In total, 451 LTRs (57%) received statins post-transplant, atorvastatin was the most commonly used statin (68%). The mean duration of statins post-transplant was 347 days (interquartile range [IQR]: 305 to 346). And 55 (7%) LTRs developed IA in the first-year post-transplant. Out of these 55 LTRs, 9 (16.3%) had received statin before developing IA. In multivariable analysis, statin use was independently associated with a lower risk of IA (P = .002, SHR 0.30, 95% confidence interval [CI] 95% .14–.64). Statin use was also associated with a lower incidence of post-transplant Aspergillus colonization, 114 (34%) in the no statin group vs 123 (27%) in the statin group (P = .038). Conclusions The use of statin for a minimum of two weeks during the first-year post-transplant was associated with a 70% risk reduction of IA in LTRs.

Introduction Early identification of a patient with infection who may develop sepsis is of utmost importance. Unfortunately, this remains elusive because no single clinical measure or test can reflect complex pathophysiological changes in patients with sepsis. However, multiple clinical and laboratory parameters indicate impending sepsis and organ dysfunction. Screening tools using these parameters can help identify the condition, such as SIRS, quick SOFA (qSOFA), National Early Warning Score (NEWS), or Modified Early Warning Score (MEWS). We aim to externally validate qSOFA, SIRS, and NEWS/NEWS2/MEWS for in-hospital mortality among adult patients with suspected infection who presenting to the emergency department. Methods and analysis PASSEM study is an international prospective external validation cohort study. For 9 months, each participating centre will recruit consecutive adult patients who visited the emergency departments with suspected infection and are planned for hospitalisation. We will collect patients' demographics, vital signs measured in the triage, initial white blood cell count, and variables required to calculate Charlson Comorbidities Index; and follow patients for 90 days since their inclusion in the study. The primary outcome will be 30-days in-hospital mortality. The secondary outcome will be intensive care unit (ICU) admission, prolonged stay in the ICU (i.e., >72 hours), and 30- as well as 90-days all-cause mortality. The study started in December 2021 and planned to enrol 2851 patients to reach 200 in-hospital death. The sample size is adaptive and will be adjusted based on prespecified consecutive interim analyses. Ethics and dissemination The Aseer Regional Committee for Research Ethics in the General Directorate of Health Affairs-Aseer Region has approved this study. Informed consent is not required for this study due to its complete observational nature and absence of interventions or invasive procedures. We will publish study's results in peer-reviewed journals and may present them at scientific conferences.

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. I2 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 VO2 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, I2 = 53%, high quality). AT-VO2 improved with exercise rehabilitation, and heterogeneity was considered low (pooled mean difference 3.96, 95% CI 2.68–5.24, I2 = 0.0%, moderate quality). Peak VO2 and AT-VO2 are increased with aerobic exercise in CRT recipients, demonstrating a significant improvement in functional capacity.

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, P < 0.0001), were more likely to be admitted with CS (61.3 vs 41.5%, P < 0.0009), and had higher rates of vasoactive medications during their admission (69.3% vs 52.6%, P < 0.005). At discharge, there were higher rates of discharge to a HF clinic (52.0% vs 27.5%, P < 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%, P < 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. Résumé: Contexte: L’insuffisance cardiaque (IC) est un motif fréquent d’admission à l’unité de soins intensifs de cardiologie. Cette étude visait à cerner le rôle d’un service de consultation spécialisé en IC dans l’amélioration de la prise en charge de la population de patients atteinte de cette affection. Méthodologie: Un recensement de tous les patients adultes admis en 2014-2015 à l’unité de soins intensifs de cardiologie du Réseau universitaire de santé et ayant reçu un diagnostic d’IC aiguë décompensée avec ou sans choc cardiogénique a été effectué. Les caractéristiques cliniques et l’évolution de l’atteinte avaient été consignées pour ces patients. L’association, ajustée en fonction du score de propension, entre la consultation pour IC et la mortalité hospitalière a été calculée. Résultats: Au total, 285 patients uniques ont été recensés dans la cohorte. De ce nombre, 82 (28,7 %) patients sont décédés. Sur les 285 patients, 150 (52,6 %) avaient été pris en charge conjointement par un service spécialisé en IC, tandis que les 135 (47,3 %) autres ne l’avaient pas été. Les patients pris en charge par une équipe spécialisée en IC étaient plus jeunes (52,5 vs 68,0 ans, p < 0,0001), étaient plus susceptibles d’être en proie à un choc cardiogénique à l’admission (61,3 vs 41,5 %, p < 0,0009) et étaient plus nombreux à avoir reçu un agent vasoactif à l’admission (69,3 % vs 52,6 %, p < 0,005). Ils ont aussi été plus nombreux à être orientés vers une clinique spécialisée en IC à leur sortie de l’hôpital (52,0 % vs 27,5 %, p < 0,0001) et à se voir prescrire un traitement médical recommandé dans des lignes directrices. La mortalité hospitalière était plus faible chez les patients qui ont fait l’objet d’une prise en charge conjointe par une équipe spécialisée en IC (16,7 % vs 42,2 %, p < 0,0001). La consultation d’une équipe spécialisée en IC a en outre réduit le risque de réadmission de 76 % (rapport de cotes de 0,24; intervalle de confiance à 95 % : 0,13-0,47). Conclusions: Les patients pris en charge par une équipe spécialisée en IC étaient plus susceptibles d’être en proie à un choc cardiogénique à l’admission, de survivre à leur sortie de l’hôpital, de se voir prescrire un traitement médical recommandé dans des lignes directrices et de faire l’objet d’un suivi dans une clinique spécialisée en IC.

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

Background and Objectives Primary studies and systematic reviews of prognostic factors commonly analyze and report relative measures of association between the factor(s) and outcome(s) of interest. For decision making, however, guideline panelists, systematic reviewers, and health care professionals at the point of care will ultimately need the absolute risk of the outcome(s) in those with and without the prognostic factor(s) of interest. The objective of the study was to develop a framework for calculating the absolute risk of the outcome(s) in those with and without the prognostic factor(s) of interest. Methods We developed a mathematical approach to calculate the absolute risk of events from the relative measure of association, the total number of events and patients at risk, and the prevalence of the prognostic factor, all of which are usually reported in cohort studies assessing prognostic factors. We demonstrate how simpler approximations lead to biased estimates of absolute risk and thus the need for these formulas. We explain our logical framework using the simplest case, in which the measure of association is a relative risk, and provide extensions of the formula to odds ratios and hazard ratios. The same formulas can be applied to reports providing only the relative measure of association (e.g., case-control studies) by using external evidence regarding prevalence of the prognostic factor and overall risk of events. Conclusions Our proposed formulas facilitate accurate calculation of measures of absolute risk in those with and without prognostic factors of interest for studies reporting the total number of events and patients at risk, the prevalence of the prognostic factor and a relative risk, odds ratio, or hazard ratio.

Invasive fungal infections (IFI), particularly invasive aspergillosis (IA), cause significant morbidity and mortality in lung transplant (LTx) recipients. The optimum strategy and antifungal agents for prevention are unclear.We performed a comprehensive literature search, systematic review, and network meta-analysis using a frequentist framework to compare the efficacy of various antifungal drugs on the incidence of IA/IFI in the setting of universal prophylaxis or no prophylaxis following lung transplantation.We included 13 eligible studies comprising of 1515 LTx recipients and 12 different prophylaxis strategies/antifungal combinations. The greatest number of direct comparisons were between the inhaled amphotericin formulations. The top three ranked treatments were inhaled liposomal amphotericin B (L-AmB), inhaled amphotericin deoxycholate (AmBd), and itraconazole plus inhaled amphotericin B (AmB). Among the azoles, isavuconazole ranked highest. The certainty of the evidence, assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework, was very low.Although universal antifungal prophylaxis post lung transplantation is commonly used, robust data from randomized controlled trials (RCTs) to inform the choice of antifungal agent and prophylaxis strategy are lacking. This exploratory network meta-analysis provides insight into the probable relative effectiveness of various antifungal agents in preventing IA, and this analysis should serve as a guide when selecting antifungals to be assessed in a RCT.

Background and objective The prognostic value of age and other non-hematological factors in predicting outcomes in older patients with newly diagnosed acute myeloid leukemia (AML) undergoing antileukemic therapy is not well understood. We performed a systematic review to determine the association between these factors and mortality and health-related quality of life or fatigue among these patients. Methods We searched Medline and Embase through October 2021 for studies in which researchers quantified the relationship between age, comorbidities, frailty, performance status, or functional status; and mortality and health-related quality of life or fatigue in older patients with AML receiving antileukemic therapy. We assessed the risk of bias of the included studies using the Quality in Prognostic Studies tool, conducted random-effects meta-analyses, and assessed the quality of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation approach. Results We included 90 studies. Meta-analysis showed that age (per 5-year increase, HR 1.16 95% CI 1.11–1.21, high-quality evidence), comorbidities (Hematopoietic Cell Transplantation-specific Comorbidity Index: 3+ VS less than 3, HR 1.60 95% CI 1.31–1.95, high-quality evidence), and performance status (Eastern Cooperative Oncology Group/ World Health Organization (ECOG/WHO): 2+ VS less than 2, HR 1.63 95% CI 1.43–1.86, high-quality evidence; ECOG/WHO: 3+ VS less than 3, HR 2.00 95% CI 1.52–2.63, moderate-quality evidence) were associated with long-term mortality. These studies provided inconsistent and non-informative results on short-term mortality (within 90 days) and quality of life. Conclusion High-quality or moderate-quality evidence support that age, comorbidities, performance status predicts the long-term prognosis of older patients with AML undergoing antileukemic treatment.