Project description:ObjectiveCorticosteroids are a common option used in sepsis treatment. However, the efficacy and potential risk of corticosteroids in septic patients have not been well assessed. This review was performed to assess the efficacy and safety of corticosteroids in patients with sepsis.MethodsPubMed, Embase, and Cochrane library databases were searched from inception to March 2021. Randomized controlled trials (RCTs) that evaluated the effect of corticosteroids on patients with sepsis were included. The quality of outcomes in the included articles was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation methodology. The data were pooled by using risk ratio (RR) and mean difference (MD). The random-effects model was used to evaluate the pooled MD or RR and 95% confidence intervals (CIs).ResultsFifty RCTs that included 12,304 patients with sepsis were identified. Corticosteroids were not associated with the mortality in 28-day (RR, 0.94; 95% CI, 0.87-1.02; evidence rank, moderate) and long-term mortality (>60 days) (RR, 0.96; 95% CI, 0.88-1.05) in patients with sepsis (evidence rank, low). However, corticosteroids may exert a significant effect on the mortality in the intensive care unit (ICU) (RR, 0.9; 95% CI, 0.83-0.97), in-hospital (RR, 0.9; 95% CI, 0.82-0.99; evidence rank, moderate) in patients with sepsis or septic shock (evidence rank, low). Furthermore, corticosteroids probably achieved a tiny reduction in the length of hospital stay and ICU. Corticosteroids were associated with a higher risk of hypernatremia and hyperglycemia; furthermore, they appear to have no significant effect on superinfection and gastroduodenal bleeding.ConclusionsCorticosteroids had no significant effect on the 28-day and long-term mortality; however, they decreased the ICU and hospital mortality. The findings suggest that the clinical corticosteroids may be an effective therapy for patients with sepsis during the short time.Systematic review registrationhttps://inplasy.com/wp-content/uploads/2021/05/INPLASY-Protocol-1074-4.pdf.

Project description:INTRODUCTION:Sepsis is associated with a dysregulated host response to infection and impaired endogenous corticosteroid metabolism. As such, therapeutic use of exogenous corticosteroids is a promising adjunctive intervention. Despite a large number of trials examining this research question, uncertainty persists regarding the effect of corticosteroids on survival in sepsis. Several large randomised controlled trials have been published recently prompting a re-evaluation of the available literature. METHODS AND ANALYSIS:A rigorous and reproducible search and screening process from a Cochrane review on the same topic was comprehensive to October 2014. We will search MEDLINE, EMBASE, LILACS, the Cochrane trial registry and clinicaltrials.gov for eligible randomised controlled trials investigating the use of corticosteroids in patients with sepsis from September 2014. Outcomes have been chosen by a semi-independent guideline panel, created in the context of a parallel BMJ Rapid Recommendation on the topic. This panel includes clinicians, content experts, methodologists and patient representatives, who will help identify patient-important outcomes that are critical for deciding whether to use or not use corticosteroids in sepsis. Two reviewers will independently screen and identify eligible studies; a third reviewer will resolve any disagreements. We will use RevMan to pool effect estimates from included studies for each outcome using a random-effect model. We will present the results as relative risk with 95% CI for dichotomous outcomes and as mean difference or standardised mean difference for continuous outcomes with 95%?CI. We will assess the certainty of evidence at the outcome level using the Grading of Recommendations, Assessment, Development and Evaluation approach. We will conduct a priori subgroup analyses, which have been chosen by the parallel BMJ Rapid Recommendation panel. ETHICS AND DISSEMINATION:The aim of this systematic review is to summarise the updated evidence on the efficacy and safety of corticosteroids in patients with sepsis. TRIAL REGISTRATION NUMBER:CRD42017058537.

Project description:PURPOSE:Inhaled corticosteroids (ICSs) are often considered an empirical therapy in the management of patients with cough. However, ICS responsiveness is difficult to interpret in daily clinical practice, as the improvements may include placebo effects or self-remission. We aimed to evaluate ICS and placebo treatment effects in adult patients with cough. METHODS:Electronic databases were searched for studies published until June 2018, without language restriction. Randomized controlled trials reporting the effects of ICSs compared with placebo in adult patients with cough were included. Random effects meta-analyses were conducted to estimate the treatment effects. Therapeutic gain was calculated by subtracting the percentage change from baseline in the cough score in the ICS treatment group from that in the placebo treatment group. RESULTS:A total of 9 studies were identified and 8 studies measuring cough severity outcomes were included for meta-analyses. Therapeutic gain from ICSs ranged from -5.0% to +94.6% across the studies included; however, it did not exceed +22%, except for an outlier reporting very high therapeutic gains (+45.6% to +94.6%, depending on outcomes). Overall ICS treatment effects in cough severity outcomes were small-to-moderate (standardized mean difference [SMD], -0.38; 95% confidence interval [CI], -0.54, -0.23), which were comparable between subacute and chronic coughs. However, pooled placebo treatment effects were very large in subacute cough (SMD, -2.58; 95% CI, -3.03, -2.1), and modest but significant in chronic cough (SMD, -0.46; 95% CI, -0.72, -0.21). CONCLUSIONS:Overall therapeutic gain from ICSs is small-to-moderate. However, placebo treatment effects of ICS are large in subacute cough, and modest but still significant in chronic cough. These findings indicate the need for careful interpretation of ICS responsiveness in the management of cough patients in the clinic, and also for rigorous patient selection to identify ICS-responders.

Project description:Procalcitonin (PCT) has been widely investigated for its prognostic value in septic patients. However, studies have produced conflicting results. The purpose of the present meta-analysis is to explore the diagnostic accuracy of a single PCT concentration and PCT non-clearance in predicting all-cause sepsis mortality. We searched PubMed, Embase, Web of Knowledge and the Cochrane Library. Articles written in English were included. A 2 × 2 contingency table was constructed based on all-cause mortality and PCT level or PCT non-clearance in septic patients. Two authors independently evaluated study eligibility and extracted data. The diagnostic value of PCT in predicting prognosis was determined using a bivariate meta-analysis model. We used the Q-test and I2 index to test heterogeneity. Twenty-three studies with 3,994 patients were included. An elevated PCT level was associated with a higher risk of death. The pooled relative risk (RR) was 2.60 (95% confidence interval (CI), 2.05-3.30) using a random-effects model (I(2) = 63.5%). The overall area under the summary receiver operator characteristic (SROC) curve was 0.77 (95% CI, 0.73-0.80), with a sensitivity and specificity of 0.76 (95% CI, 0.67-0.82) and 0.64 (95% CI, 0.52-0.74), respectively. There was significant evidence of heterogeneity for the PCT testing time (P = 0.020). Initial PCT values were of limited prognostic value in patients with sepsis. PCT non-clearance was a prognostic factor of death in patients with sepsis. The pooled RR was 3.05 (95% CI, 2.35-3.95) using a fixed-effects model (I(2) = 37.9%). The overall area under the SROC curve was 0.79 (95% CI, 0.75-0.83), with a sensitivity and specificity of 0.72 (95% CI, 0.58-0.82) and 0.77 (95% CI, 0.55-0.90), respectively. Elevated PCT concentrations and PCT non-clearance are strongly associated with all-cause mortality in septic patients. Further studies are needed to define the optimal cut-off point and the optimal definition of PCT non-clearance for accurate risk assessment.

Project description:BACKGROUND:Angiopoietin-1 (Ang-1) and 2 (Ang-2), high mobility group box 1 (HMGB1), soluble receptor for advanced glycation endproducts (sRAGE), soluble triggering receptor expressed on myeloid cells 1 (sTREM1), and soluble urokinase-type plasminogen activator receptor (suPAR) have shown promising results for predicting all-cause mortality in critical care patients. The aim of our systematic review and meta-analysis was to assess the prognostic value of these biomarkers for mortality in adult patients with sepsis. METHODS:A systematic literature search of the MEDLINE, PubMed, EMBASE, and Cochrane Library databases, for articles in English published from 01.01.1990 onwards, was conducted. The systematic review focused exclusively on observational studies of adult patients with sepsis, any randomized trials were excluded. For the meta-analysis, only studies which provide biomarker concentrations within 24 h of admission in sepsis survivors and nonsurvivors were included. Results are presented as pooled mean differences (MD) between nonsurvivors and survivors with 95% confidence interval for each of the six biomarkers. Studies not included in the quantitative analysis were narratively summarized. The risk of bias was assessed in all included studies using the Quality in Prognosis Studies (QUIPS) tool. RESULTS:The systematic literature search retrieved 2285 articles. In total, we included 44 studies in the qualitative analysis, of which 28 were included in the meta-analysis. The pooled mean differences in biomarker concentration (nonsurvivors - survivors), measured at onset of sepsis, are listed as follows: (1) Ang-1: -?2.9 ng/ml (95% CI -?4.1 to -?1.7, p?<?0.01); (2) Ang-2: 4.9 ng/ml (95% CI 2.6 to 7.1, p?<?0.01); (3) HMGB1: 1.2 ng/ml (95% CI 0.0 to 2.4, p?=?0.05); (4) sRAGE: 1003 pg/ml (95% CI 628 to 1377, p?<?0.01); (5) sTREM-1: 87 pg/ml (95% CI 2 to 171, p?=?0.04); (6) suPAR: 5.2 ng/ml (95% CI 4.5 to 6.0, p?<?0.01). CONCLUSIONS:Ang-1, Ang-2, and suPAR provide beneficial prognostic information about mortality in adult patients with sepsis. The further development of standardized assays and the assessment of their performance when included in panels with other biomarkers may be recommended. Trial registration This study was recorded on PROSPERO, prospective register of systematic reviews, under the registration ID: CRD42018081226.

Project description:Importance:Although corticosteroids are widely used for adults with sepsis, both the overall benefit and potential risks remain unclear. Objective:To conduct a systematic review and meta-analysis of the efficacy and safety of corticosteroids in patients with sepsis. Data Sources and Study Selection:MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception until March 20, 2018, and updated on August 10, 2018. The terms corticosteroids, sepsis, septic shock, hydrocortisone, controlled trials, and randomized controlled trial were searched alone or in combination. Randomized clinical trials (RCTs) were included that compared administration of corticosteroids with placebo or standard supportive care in adults with sepsis. Data Extraction and Synthesis:Meta-analyses were conducted using a random-effects model to calculate risk ratios (RRs) and mean differences (MDs) with corresponding 95% CIs. Two independent reviewers completed citation screening, data abstraction, and risk assessment. Main Outcomes and Measures:Twenty-eight-day mortality. Results:This meta-analysis included 37 RCTs (N = 9564 patients). Eleven trials were rated as low risk of bias. Corticosteroid use was associated with reduced 28-day mortality (RR, 0.90; 95% CI, 0.82-0.98; I2 = 27%) and intensive care unit (ICU) mortality (RR, 0.85; 95% CI, 0.77-0.94; I2 = 0%) and in-hospital mortality (RR, 0.88; 95% CI, 0.79-0.99; I2 = 38%). Corticosteroids were significantly associated with increased shock reversal at day 7 (MD, 1.95; 95% CI, 0.80-3.11) and vasopressor-free days (MD, 1.95; 95% CI, 0.80-3.11) and with ICU length of stay (MD, -1.16; 95% CI, -2.12 to -0.20), the sequential organ failure assessment score at day 7 (MD, -1.38; 95% CI, -1.87 to -0.89), and time to resolution of shock (MD, -1.35; 95% CI, -1.78 to -0.91). However, corticosteroid use was associated with increased risk of hyperglycemia (RR, 1.19; 95% CI, 1.08-1.30) and hypernatremia (RR, 1.57; 95% CI, 1.24-1.99). Conclusions and Relevance:The findings suggest that administration of corticosteroids is associated with reduced 28-day mortality compared with placebo use or standard supportive care. More research is needed to associate personalized medicine with the corticosteroid treatment to select suitable patients who are more likely to show a benefit.

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Corrigendum: Corticosteroids for Treating Sepsis in Adult Patients: A Systematic Review and Meta-Analysis.

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