Performance of early warning assessment tools in predicting mortality among patients with sepsis: a systematic review and network meta-analysis

Indirect treatment comparisons and biologics

Corticosteroids for treating sepsis: A systematic review and network meta-analysis.

Introduction:Acute infection in post-disaster settings is associated with increased morbidity and mortality. Sepsis management in low resource settings is controversial with recent research suggesting that aggressive fluid resuscitation may cause greater harm than benefit. However, the vast majority of international sepsis guidelines still suggest large initial fluid boluses as part of sepsis algorithms.Aim:To create an adult and pediatric sepsis algorithm to be applied in low resource clinical settings. This is part of a larger project to create clinical algorithms to provide standardization of emergency case management for low-resource clinical environments.Methods:A literature search was performed through PubMed identifying and reviewing fluid resuscitation in adult and pediatric sepsis patients in high and low resource clinical environments. The pathways were created based on interpretation of the available evidence-based literature. Focus groups were conducted in Zambia in March 2018 for feedback from local practitioners regarding feasibility of pathways. The pathways were then modified, reviewed by experts peer-review and revised.Results:Final pediatric and adult sepsis clinical algorithms were created and posted to the free web-based application AgileMD™. They will be available via app access, an online platform, or printable pathways for use in the clinical environment.Discussion:The study is currently undergoing IRB approval with a plan for implementation of multiple clinical algorithms at a referral hospital site in Zambia in January 2019. Site direction at Ndola Hospital will be conducted under the leadership of an Emergency Medicine trained physician, who will assist in implementation of algorithms and collection of data. Initial data review will be conducted in May 2019. There will be incremental site visits by organizing researchers throughout the implementation and data collection period. Statistical analysis will examine sepsis associated processes and outcome indicators pre and post-intervention to further delineate sepsis management in low resource clinical environments.

BackgroundExisting scoring systems have limitations in predicting the in-hospital mortality of adult sepsis patients. We aimed to develop and validate a novel risk score for predicting the in-hospital mortality of adult sepsis patients.MethodsThe clinical data of 1,335 adult sepsis inpatients were retrospectively analyzed. Enrolled patients were randomly divided into a modeling group and a validation group at a 3:2 ratio. The modeling group (n=801) was used to develop the risk score by univariate and multivariate logistic regression analyses. The score’s performance was validated in the validation group (n=534). We classified patients into four risk levels according to the novel risk score.ResultsAge, central vein catheterization, mechanical ventilation, vasopressin, Charlson comorbidity index (CCI), respiratory rate (RR), heart rate (HR), Glasgow coma scale (GCS) score, platelet (PLT), hematocrit (HCT), aspartate aminotransferase (AST), and activated partial thrombin time (APTT) were independent risk factors for in-hospital death in adult sepsis patients. Continuous variables were converted into classified variables to develop the risk score, with a total score of 39 points. Adult sepsis patients with low, lower medium, higher medium, and high risk levels had in-hospital mortality rates of 9.8%, 24.7%, 55.8%, and 83.5%, respectively.ConclusionsCompared with the Acute Physiology and Chronic Health Evaluation II scoring system (APACHE II) and the Modified Early Warning Score (MEWS), the novel risk score showed good predictive performance for in-hospital mortality in adult sepsis patients.

A recent prospective meta-analysis demonstrated that interleukin-6 antagonists are associated with lower all-cause mortality in hospitalised patients with COVID-19, compared with usual care or placebo. However, emerging evidence suggests that clinicians are favouring the use of tocilizumab over sarilumab. A new randomised comparison of these agents from the REMAP-CAP trial shows similar effects on in-hospital mortality. Therefore, we initiated a network meta-analysis, to estimate pairwise associations between tocilizumab, sarilumab and usual care or placebo with 28-day mortality, in COVID-19 patients receiving concomitant corticosteroids and ventilation, based on all available direct and indirect evidence. Eligible trials randomised hospitalised patients with COVID-19 that compared tocilizumab or sarilumab with usual care or placebo in the prospective meta-analysis or that directly compared tocilizumab with sarilumab. Data were restricted to patients receiving corticosteroids and either non-invasive or invasive ventilation at randomisation. Pairwise associations between tocilizumab, sarilumab and usual care or placebo for all-cause mortality 28 days after randomisation were estimated using a frequentist contrast-based network meta-analysis of odds ratios (ORs), implementing multivariate fixed-effects models that assume consistency between the direct and indirect evidence. One trial (REMAP-CAP) was identified that directly compared tocilizumab with sarilumab and supplied results on all-cause mortality at 28-days. This network meta-analysis was based on 898 eligible patients (278 deaths) from REMAP-CAP and 3710 eligible patients from 18 trials (1278 deaths) from the prospective meta-analysis. Summary ORs were similar for tocilizumab [0·82 [0·71-0·95, p = 0·008]] and sarilumab [0·80 [0·61-1·04, p = 0·09]] compared with usual care or placebo. The summary OR for 28-day mortality comparing tocilizumab with sarilumab was 1·03 [95%CI 0·81-1·32, p = 0·80]. The p-value for the global test of inconsistency was 0·28. Administration of either tocilizumab or sarilumab was associated with lower 28-day all-cause mortality compared with usual care or placebo. The association is not dependent on the choice of interleukin-6 receptor antagonist.

Association between vitamin E and 28-day mortality in adult sepsis patients: A retrospective cohort analysis.

BackgroundSerotonin (5-HT3) receptor antagonists are a class of antiemetic medications often used to prevent nausea and vomiting among patients undergoing chemotherapy, radiotherapy or surgery. However, recent studies suggest that these agents might be associated with increased cardiac harm. To examine this further, we are proposing to conduct a systematic review and network meta-analysis on the comparative safety of 5-HT3 receptor antagonists among patients undergoing chemotherapy or surgery.Methods/DesignStudies reporting one or more safety outcomes of interest for 5-HT3 receptor antagonists compared with each other, placebo, and/or other anti-emetic agents (for example, benzamides, phenothiazines, butyrophenones, antihistamines, and anticholinergics) among children and adult patients undergoing surgery or chemotherapy will be included. Our primary outcome of interest is arrhythmia. Our secondary outcomes include cardiac death, QT prolongation, PR prolongation, all-cause mortality, nausea, and vomiting. We will include experimental studies, quasi-experimental studies (namely controlled before-after and interrupted time series), and observational studies (namely cohort studies). We will not limit inclusion by publication status, time period, duration of follow-up or language of dissemination.Electronic databases (for example, MEDLINE, EMBASE) will be searched from inception onwards. These main searches will be supplemented by searching for difficult to locate and unpublished studies, such as dissertations, and governmental reports. The eligibility criteria will be pilot-tested and subsequently used to screen the literature search results by two reviewers in duplicate. A similar process will be followed for full-text screening, data abstraction, and risk of bias/methodological quality appraisal. The Cochrane Risk of Bias tool will be used to appraise experimental and quasi-experimental studies, and cohort studies will be assessed using the Newcastle Ottawa Scale. If the data allows, random effects meta-analysis and a network (that is, mixed treatment comparisons) meta-analysis will be conducted. All analyses will be conducted separately for different study designs, patient populations (for example, children and adults), and reason for administering 5-HT3 receptor antagonists (for example, post-surgery and chemotherapy).DiscussionOur results will help inform patients, clinicians, and health policy-makers about the potential safety concerns, as well as the comparative safety, of using these antiemetic agents.Trial registrationPROSPERO registry number:CRD42013003564

Clinical significance of combined tumour-infiltrating lymphocytes and microsatellite instability status in colorectal cancer: a systematic review and network meta-analysis

ObjectiveTo examine whether the continuous updating of networks of prospectively planned randomised controlled trials (RCTs) (“living” network meta-analysis) provides strong evidence against the null hypothesis in comparative effectiveness of medical...

I n their article, Wyles et al. have compared different THA bearing surfaces in terms of probability of revision using network meta-analysis (NMA) [5]. NMA is appealing because it allows the comparison of multiple healthcare interventions for a given condition—even when no direct comparisons (head-to-head trials) exist between some of those interventions—by combining the direct evidence with indirect evidence across randomized trials using the same comparator. Because of its appeals, NMA is gaining traction; however, NMA remains a relatively new approach, and the papers using it suffer from inconsistent terminology and heterogeneous reporting [1]. Many researchers and surgeons may be unfamiliar with NMA, and its related concepts and assumptions. Crucial assumptions relate to homogeneity among individual trials involving the same comparison, as in classical meta-analysis, but homogeneity also comes into play in NMA where indirect evidence is concerned. Indirect evidence refers to the results arising from the network—the ‘‘N’’ in ‘‘NMA’’—that allows the comparison of two treatments even when they have not been evaluated directly against one another in head-to-head trials. For example, in a NMA involving treatments A, B, and C, direct evidence for the comparison of treatment A to treatment C refers to trials which compared A to C, and indirect evidence refers to information that can be deduced from trials comparing treatments A to B, and treatments B to C. Issues pertaining to indirect evidence involve both statistical and conceptual aspects. For instance, transitivity implies that there are no differences in treatment-effect modifiers among studies, which may have affected the direct treatment effect estimates used to derive the indirect evidence for a comparison. The related statistical aspect is consistency or coherence, which implies that the direct and indirect treatment This CORR Insights is a commentary on the article ‘‘There Are No Differences in Shortto Mid-term Survivorship Among Total Hipbearing Surface Options: A Network Metaanalysis’’ by Wyles and colleagues available at: DOI: 10.1007/s11999-014-4065. The author certifies that he, or any member of his immediate family, has no funding or commercial associations (eg, consultancies, stock ownership, equity interest, patent/ licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research editors and board members are on file with the publication and can be viewed on request. The opinions expressed are those of the writers, and do not reflect the opinion or policy of CORR or the Association of Bone and Joint Surgeons. This CORR Insights comment refers to the article available at DOI: 10.1007/s11999014-4065. R. Porcher PhD (&) Center of Clinical Epidemiology, Hopital Hotel-Dieu, 1 Parvis Notre-Dame Place Jean-Paul II, 75004 Paris, France e-mail: raphael.porcher@htd.aphp.fr CORR Insights Published online: 23 January 2015 The Association of Bone and Joint Surgeons1 2015

81: Increased Outcome Effectiveness of the Surviving Sepsis Campaign Severe Sepsis Resuscitation Bundle With the Addition of Lactate Clearance as a Bundle Element: A Multi-National Evaluation for the ATLAS Investigators

Prognostic valule of vasoactive drug score, NT-proBNP, and blood lactate level at 6h post-admission in adult sepsis patients:A single-center, retrospective study.

Efficacy and safety of treatment modalities for cesarean scar pregnancy: a systematic review and network meta-analysis

ObjectivesTo systematically compare the effects of various antithrombotic strategies on prespecified outcomes including 28-day all-cause mortality (primary outcome), major thrombotic events and major bleeding events (secondary outcomes) in adult COVID-19 patients.DesignSystematic review and Bayesian network meta-analysis (NMA).Data sourcesPubMed, Web of Science, Embase, Cochrane Library and ClinicalTrials.gov up to February 2024.Eligibility criteriaWe included randomised controlled trials (RCTs; published in English) comparing different antithrombotic strategies (eg, anticoagulants, antiplatelet (AP) agents, fibrinolytics or combinations) in adults (aged≥18 years) with laboratory-confirmed SARS-CoV-2 infection. Eligible trials had at least one active antithrombotic arm versus another strategy or standard care.Data extraction and synthesisTwo reviewers independently extracted data using a standardised form; disagreements were resolved by consensus or third-party adjudication. Bayesian NMA was performed using Markov chain Monte Carlo methods with random/fixed effects models selected by the deviance information criterion. The risk of bias (RoB) was assessed using the Cochrane Collaboration’s tool. The confidence in NMA framework was used to assess the quality of evidence.Results35 RCTs that randomly assigned 39 949 participants were included in the main analysis. Primary outcome: evidence of low to moderate certainty suggested that, compared with standard of care (SoC), both prophylactic-dose anticoagulation (PA) (risk ratio (RR) 0.71, 95% credible interval (CrI) 0.44 to 0.99) and therapeutic-dose anticoagulation (TA; RR 0.65, 95% CrI 0.38 to 0.94) reduced the 28-day all-cause mortality. Secondary outcomes: TA (RR 0.19, 95% CrI 0.09 to 0.31), TA+AP (RR 0.27, 95% CrI 0.05 to 0.95), PA (RR 0.33, 95% CrI 0.18 to 0.53) and AP+PA (RR 0.52, 95% CrI 0.25 to 0.94) were effective in reducing major thrombotic events. AP was associated with an increased risk of major bleeding events (RR 2.27, 95% CrI 1.01 to 5.07). Subgroup analyses by hospitalisation status showed that PA significantly reduced 28-day mortality versus SoC (RR 0.52, 95% CrI 0.26 to 0.90) for non-hospitalised patients, whereas no strategies showed significant benefit in hospitalised patients. Subgroup analysis based on severity of hospitalised patients indicated that TA was more favourable than PA in decreasing the 28-day mortality in non-critically ill patients (fixed-effect model: RR 0.75, 95% CI 0.61 to 0.91; random-effect model: RR 0.71, 95% CI 0.48 to 1.05), but for critically ill patients, all antithrombotic strategies showed no significant difference.ConclusionsOur NMA indicates that both PA and TA reduced the 28-day all-cause mortality of adult COVID-19 patients. However, subgroup analyses revealed substantial heterogeneity, and the benefit may differ across hospitalisation status and disease severity.PROSPERO registration numberCRD42022355213.

OP0072 Comparative effectiveness of injection therapies in lateral epicondylitis: A systematic review and network meta-analysis of randomized controlled trials