Christophe Alberic Marti

Systemic thrombolytic therapy for acute pulmonary embolism: a systematic review and meta-analysis

Aim Thrombolytic therapy induces faster clot dissolution than anticoagulation in patients with acute pulmonary embolism (PE) but is associated with an increased risk of haemorrhage. We reviewed the risks and benefits of thrombolytic therapy in the management of patients with acute PE. Methods and results We systematically reviewed randomized controlled studies comparing systemic thrombolytic therapy plus anticoagulation with anticoagulation alone in patients with acute PE. Fifteen trials involving 2057 patients were included in our meta-analysis. Compared with heparin, thrombolytic therapy was associated with a significant reduction of overall mortality (OR; 0.59, 95% CI: 0.36–0.96). This reduction was not statistically significant after exclusion of studies including high-risk PE (OR; 0.64, 95% CI: 0.35–1.17). Thrombolytic therapy was associated with a significant reduction in the combined endpoint of death or treatment escalation (OR: 0.34, 95% CI: 0.22–0.53), PE-related mortality (OR: 0.29; 95% CI: 0.14–0.60) and PE recurrence (OR: 0.50; 95% CI: 0.27–0.94). Major haemorrhage (OR; 2.91, 95% CI: 1.95–4.36) and fatal or intracranial bleeding (OR: 3.18, 95% CI: 1.25–8.11) were significantly more frequent among patients receiving thrombolysis. Conclusions Thrombolytic therapy reduces total mortality, PE recurrence, and PE-related mortality in patients with acute PE. The decrease in overall mortality is, however, not significant in haemodynamically stable patients with acute PE. Thrombolytic therapy is associated with an increase of major and fatal or intracranial haemorrhage.

Alternative intubation techniques vs Macintosh laryngoscopy in patients with cervical spine immobilization: systematic review and meta-analysis of randomized controlled trials

Background. Immobilization of the cervical spine worsens tracheal intubation conditions. Various intubation devices have been tested in this setting. Their relative usefulness remains unclear. Methods. We searched MEDLINE, EMBASE, and the Cochrane Library for randomized controlled trials comparing any intubation device with the Macintosh laryngoscope in human subjects with cervical spine immobilization. The primary outcome was the risk of tracheal intubation failure at the first attempt. Secondary outcomes were quality of glottis visualization, time until successful intubation, and risk of oropharyngeal complications. Results. Twenty-four trials (1866 patients) met inclusion criteria. With alternative intubation devices, the risk of intubation failure was lower compared with Macintosh laryngoscopy [risk ratio (RR) 0.53; 95% confidence interval (CI) 0.35–0.80]. Meta-analyses could be performed for five intubation devices (Airtraq, Airwayscope, C-Mac, Glidescope, and McGrath). The Airtraq was associated with a statistically significant reduction of the risk of intubation failure at the first attempt (RR 0.14; 95% CI 0.06–0.33), a higher rate of Cormack–Lehane grade 1 (RR 2.98; 95% CI 1.94–4.56), a reduction of time until successful intubation (weighted mean difference −10.1 s; 95% CI −3.2 to −17.0), and a reduction of oropharyngeal complications (RR 0.24; 95% CI 0.06–0.93). Other devices were associated with improved glottis visualization but no statistically significant differences in intubation failure or time to intubation compared with conventional laryngoscopy. Conclusions. In situations where the spine is immobilized, the Airtraq device reduces the risk of intubation failure. There is a lack of evidence for the usefulness of other intubation devices.

Adjunctive Corticotherapy for Community Acquired Pneumonia: A Systematic Review and Meta-Analysis

Background Community-acquired pneumonia (CAP) induces lung and systemic inflammation, leading to high morbidity and mortality. We systematically reviewed the risks and benefits of adjunctive corticotherapy in the management of patients with CAP. Methods We systematically searched Pubmed, Embase and the Cochrane Library for randomized controlled trials comparing adjunctive corticotherapy and antimicrobial therapy with antimicrobial therapy alone in patients with CAP. The primary outcome was 30-day mortality. Secondary outcomes were length of hospital stay, time to clinical stability and severe complications. Results 14 trials (2077 patients) were included. The reported 30-day mortality was 7.9% (80/1018) among patients treated with adjunctive corticotherapy versus 8.3% (85/1028) among patients treated with antimicrobial therapy alone (RR 0.84; 95%CI 0.55 to1.29). Adjunctive corticotherapy was associated with a reduction of severe complications (RR 0.36; 95%CI 0.23 to 0.56), a shorter length of stay (9.0 days; 95%CI 7.6 to 10.7 vs 10.6 days; 95%CI 7.4 to 15.3) and a shorter time to clinical stability (3.3 days; 95% CI 2.8 to 4.1 vs 4.3 days; 95%CI 3.6 to 5.1). The risk of hyperglycemia was higher among patients treated with adjunctive corticotherapy (RR 1.59; 95%CI 1.06 to 2.38), whereas the risk of gastro-intestinal bleeding was similar (RR 0.83; 95%CI 0.35 to 1.93). In the subgroup analysis based on CAP severity, a survival benefit was found among patients with severe CAP (RR 0.47; 95%CI 0.23 to 0.96). Conclusion Adjunctive corticotherapy is associated with a reduction of length of stay, time to clinical stability, and severe complications among patients with CAP, but the effect on mortality remains uncertain.

Is diabetes mellitus a risk factor for venous thromboembolism? A systematic review and meta-analysis of case–control and cohort studies

OBJECTIVE Diabetes mellitus is a well-established risk factor for atherosclerotic disease, but its role in the occurrence of venous thromboembolism (VTE) has not been elucidated. We conducted a meta-analysis of published cohort and case-control studies to assess whether diabetes mellitus is a risk factor for VTE. RESEARCH DESIGN AND METHODS We systematically searched MEDLINE and EMBASE for case-control and prospective cohort studies assessing association between the risk of venous thromboembolism and diabetes. Odds ratios (OR) from case-control studies were combined while for prospective studies hazard ratios (HR) were combined. Models with random effects were used. Meta-analyses were conducted separately for raw and adjusted measures of association. RESULTS 24 studies were identified including 10 cohort studies (274,501 patients) and 14 case-control studies (1,157,086 patients). Meta-analysis of the prospective cohort studies demonstrated a significant association between diabetes and VTE (HR 1.60; 95% CI 1.35 to 1.89). This association was no longer present after analysis of multi-adjusted HRs (HR 1.10; 95% CI 0.77 to 1.56). Meta-analysis of case-control studies showed a significant association between diabetes and VTE (OR 1.57; 95%CI 1.17 to 2.12), but this association was no longer present when adjusted ORs were used (OR 1.18; 95%CI 0.89 to 1.56). CONCLUSIONS The increased risk of VTE associated with diabetes mainly results from confounders rather than an intrinsic effect of diabetes on venous thrombotic risk. Therefore, no specific recommendations should apply for the management of diabetic patients at risk for VTE.

Hemodynamic indexes derived from computed tomography angiography to predict pulmonary embolism related mortality.

Pulmonary embolism (PE) induces an acute increase in the right ventricle afterload that can lead to right-ventricular dysfunction (RVD) and eventually to circulatory collapse. Hemodynamic status and presence of RVD are important determinants of adverse outcomes in acute PE. Technologic progress allows computed tomography angiography (CTA) to give more information than accurate diagnosis of PE. It may also provide an insight into hemodynamics and right-ventricular function. Proximal localization of emboli, reflux of contrast medium to the hepatic veins, and right-to-left short-axis ventricular diameter ratio seem to be the most relevant CTA predictors of 30-day mortality. These elements require little postprocessing time, an advantage in the emergency room. We herein review the prognostic value of RVD and other CTA mortality predictors for patients with acute PE.

Predictors and Implications of Early Clinical Stability in Patients Hospitalized for Moderately Severe Community-Acquired Pneumonia

Background Assessment of early response to treatment is crucial for the management of community-acquired pneumonia (CAP). Objective To describe the predictors and the outcomes of early clinical stability Methods We did a secondary analysis of a multicentre randomized controlled trial on CAP treatment in which 580 patients hospitalized for moderately severe CAP were included. The association between demographic, clinical and biological variables available at inclusion and early clinical stability (stabilization of vital signs within 72 hours with predetermined cut-offs) was assessed by multivariate logistic regression. The association between early clinical stability and mortality, severe adverse events, and length of stay was also tested. Results Younger age (OR 0.98, 95% CI 0.96–0.99), lower platelet count (OR per 10 G/L increment 0.96, 95% CI 0.94–0.98), lower respiratory rate (OR 0.94, 95% CI 0.90–0.97), absence of hypoxemia (OR 0.58, 95% CI 0.40–0.85), lower numbers of co-morbid conditions (OR 0.82, 95% CI 0.69–0.98) and signs or symptoms (OR 0.78, 95% CI 0.68–0.90) were significantly associated with early clinical stability. Patients with early clinical stability had lower 90-days mortality (3.4% vs. 11.9%, p<0.001), fewer admissions to the intensive care unit (2.7% vs. 8.0%, p = 0.005) and a shorter length of stay (6.0 days, IQR 4.0–10.0 vs. 10.0 days, IQR 7.0–15.0, p<0.001). Conclusions Patients with younger age, less co-morbidity, fewer signs or symptoms, less respiratory compromise, and a lower platelet count are more likely to reach early clinical stability. Patients without early clinical stability have a worse prognosis and warrant close scrutiny.

Safety and efficacy of tenecteplase versus alteplase in acute coronary syndrome: a systematic review and meta-analysis of randomized trials

Introduction Alteplase and tenecteplase are two widely used thrombolytic agents and are both approved for the treatment of acute myocardial infarction. These two molecules have increased fibrin specificity compared with older thrombolytics but distinct pharmacokinetic properties and may differ in terms of risks and benefits. We decided to review the available evidence comparing the safety and efficacy of these two molecules in acute coronary syndrome (ACS) or pulmonary embolism (PE). Material and methods To compare the efficacy and safety profile of alteplase and tenecteplase, we systematically searched PubMed, Cochrane and Embase for randomized studies comparing weight-adjusted alteplase to weight-adjusted tenecteplase in patients with ACS or PE. The primary endpoint was the risk of major bleeding, and secondary endpoints were risk of intracranial haemorrhage (ICH), vessel recanalization and 30-day mortality. Results Three studies including 17,325 patients with ACS were included in a quantitative meta-analysis. No study compared alteplase to tenecteplase in acute PE. Tenecteplase was associated with a statistically significant reduction of the risk of major bleeding compared to alteplase (RR = 0.79; 95% CI: 0.69–0.90, p = 0.0002). The risk of intracranial haemorrhage (RR = 0.96; 95% CI: 0.71–1.31, p = 0.82) and 30-day mortality (RR = 1.02; 95% CI: 0.9–1.15) were similar in patients treated with alteplase or tenecteplase. No difference was observed in the rate of vessel recanalization. Conclusions The available evidence suggests that tenecteplase is associated with a reduced risk of major bleeding compared to alteplase in ACS without evidence of reduced efficacy. These results are however mainly dependent on a single study.

Time to antibiotics administration and outcome in community-acquired pneumonia: Secondary analysis of a randomized controlled trial

BACKGROUND The association between early antibiotic administration and outcomes remains controversial in patients hospitalized for community-acquired pneumonia. METHODS We performed a secondary analysis of a randomized controlled trial comparing two antibiotic treatment strategies for patients hospitalized for moderately severe CAP. The univariate and multivariate associations between time to antibiotic administration (TTA) and time to clinical stability were assessed using a Cox proportional hazard model. Secondary outcomes were death, intensive care unit admission and hospital readmission up to 90days. RESULTS 371 patients (mean age 76years, CURB-65 score≥2 in 52%) were included. Mean TTA was 4.35h (SD 3.48), with 58.5% of patients receiving the first antibiotic dose within 4h. In multivariate analysis, number of symptoms and signs (HR 0.876, 95% CI 0.784-0.979, p=0.020), age (HR 0.986, 95% CI 0.975-0.996, p=0.007), initial heart rate (HR 0.992, 95% CI 0.986-0.999, p=0.023), and platelets count (HR 0.998, 95% CI 0.996-0.999, p=0.004) were associated with a reduced probability of reaching clinical stability. The association between TTA and time to clinical stability was not significant (HR 1.009, 95% CI 0.977-1.042, p=0.574). We found no association between TTA and the risk of intensive care unit admission, death or readmission up to 90days after the initial admission. CONCLUSION In patients hospitalized for moderately severe CAP, a shorter time to antibiotic administration was not associated with a favorable outcome. These findings support the current recommendations that do not assign a specific time frame for antibiotics administration.

Clinical features of anaerobic orthopaedic infections

Abstract Some patient populations and types of orthopaedic surgery could be at particular risk for anaerobic infections. In this retrospective cohort study of operated adult patients with infections from 2004 to 2014, we assessed obligate anaerobes and considered first clinical infection episodes. Anaerobes, isolated from intra-operative samples, were identified in 2.4% of 2740 surgical procedures, of which half (33/65; 51%) were anaerobic monomicrobial infections. Propionibacterium acnes, a penicillin and vancomycin susceptible pathogen, was the predominantly isolated anaerobe. By multivariate analysis, the presence of fracture fixation plates was the variable most strongly associated with anaerobic infection (odds ratio: 2.1, 95% CI: 1.3–3.5). Anaerobes were also associated with spondylodesis and polymicrobial infections. In contrast, it revealed less likely in native bone or prosthetic joint infections and was not related to prior antibiotic use. In conclusion, obligate anaerobes in our case series of orthopaedic infections were rare, and mostly encountered in infections related to trauma with open-fracture fixation devices rather than clean surgical site infection. Anaerobes were often co-pathogens, and cultures most frequently recovered P. acnes. These observations thus do not support changes in current practices such as broader anaerobe coverage for perioperative prophylaxis.

Reliability of the revised Swiss Emergency Triage Scale: a computer simulation study.

Background The Swiss Emergency Triage Scale (SETS) is a four-level emergency scale that previously showed moderate reliability and high rates of undertriage due to a lack of standardization. It was revised to better standardize the measurement and interpretation of vital signs during the triage process. Objective The aim of this study was to explore the inter-rater and test–retest reliability, and the rate of correct triage of the revised SETS. Patients and methods Thirty clinical scenarios were evaluated twice at a 3-month interval using an interactive computerized triage simulator by 58 triage nurses at an urban teaching emergency department admitting 60 000 patients a year. Inter-rater and test–retest reliabilities were determined using &kgr; statistics. Triage decisions were compared with a gold standard attributed by an expert panel. Rates of correct triage, undertriage, and overtriage were computed. A logistic regression model was used to identify the predictors of correct triage. Results A total of 3387 triage situations were analyzed. Inter-rater reliability showed substantial agreement [mean &kgr;: 0.68; 95% confidence interval (CI): 0.60–0.78] and test–retest almost perfect agreement (mean &kgr;: 0.86; 95% CI: 0.84–0.88). The rate of correct triage was 84.1%, and rates of undertriage and overtriage were 7.2 and 8.7%, respectively. Vital sign measurement was an independent predictor of correct triage (odds ratios for correct triage: 1.29 for each additional vital sign measured, 95% CI: 1.20–1.39). Conclusion The revised SETS incorporating standardized vital sign measurement and interpretation during the triage process resulted in high reliability and low rates of mistriage.