Diaphragm and Lung Ultrasound to Predict Weaning Outcome: Systematic Review and Meta-Analysis.

BACKGROUND: Deciding the optimal timing for extubation in patients who are mechanically ventilated can be challenging, and traditional weaning predictor tools are not very accurate. The aim of this systematic review and meta-analysis was to assess the accuracy of lung and diaphragm ultrasound for predicting weaning outcomes in critically ill adults. METHODS: MEDLINE, the Cochrane Library, Web of Science, Scopus, LILACS, Teseo, Tesis Doctorales en Red, and OpenGrey were searched, and the bibliographies of relevant studies were reviewed. Two researchers independently selected studies that met the inclusion criteria and assessed study quality in accordance with the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The summary receiver-operating characteristic curve and pooled diagnostic OR (DOR) were estimated by using a bivariate random effects analysis. Sources of heterogeneity were explored by using predefined subgroup analyses and bivariate meta-regression. RESULTS: Nineteen studies involving 1,071 people were included in the study. For diaphragm thickening fraction, the area under the summary receiver-operating characteristic curve was 0.87, and DOR was 21 (95% CI, 11-40). Regarding diaphragmatic excursion, pooled sensitivity was 75% (95% CI, 65-85); pooled specificity, 75% (95% CI, 60-85); and DOR, 10 (95% CI, 4-24). For lung ultrasound, the area under the summary receiver-operating characteristic curve was 0.77, and DOR was 38 (95% CI, 7-198). Based on bivariate meta-regression analysis, a significantly higher specificity for diaphragm thickening fraction and higher sensitivity for diaphragmatic excursion was detected in studies with applicability concerns. CONCLUSIONS: Lung and diaphragm ultrasound can help predict weaning outcome, but its accuracy may vary depending on the patient subpopulation.

Predictive power of the grace score in population with diabetes.

INTRODUCTION: Current clinical practice guidelines recommend risk stratification in patients with acute coronary syndrome (ACS) upon admission to hospital. Diabetes mellitus (DM) is widely recognized as an independent predictor of mortality in these patients, although it is not included in the GRACE risk score. OBJECTIVES: The objective of this study is to validate the GRACE risk score in a contemporary population and particularly in the subgroup of patients with diabetes, and to test the effects of including the DM variable in the model. MATERIAL AND METHODS: Retrospective cohort study in patients included in the ARIAM-SEMICYUC registry, with a diagnosis of ACS and with available in-hospital mortality data. We tested the predictive power of the GRACE score, calculating the area under the ROC curve. We assessed the calibration of the score and the predictive ability based on type of ACS and the presence of DM. Finally, we evaluated the effect of including the DM variable in the model by calculating the net reclassification improvement. RESULTS: The GRACE score shows good predictive power for hospital mortality in the study population, with a moderate degree of calibration and no significant differences based on ACS type or the presence of DM. Including DM as a variable did not add any predictive value to the GRACE model. CONCLUSIONS: The GRACE score has an appropriate predictive power, with good calibration and clinical applicability in the subgroup of diabetic patients.

GRACE Score Validation in Predicting Hospital Mortality: Analysis of the Role of Sex.

Background: The GRACE (Global Registry of Acute Coronary Events) risk score is recommended for risk stratification in acute coronary syndrome (ACS). It does not include sex, a variable strongly associated with ACS prognosis. The aim of this study was to examine if sex adds prognostic information to the GRACE score in a contemporary population. Materials and Methods: Analysis of discrimination and calibration of GRACE score in the validation population, derived from the ARIAM-SEMICYUC registry (2012-2015). Outcome was hospital mortality. The uniformity of fit of the score was tested in predefined subpopulations: with and without ST-segment elevation myocardial infarction (STEMI and NSTEMI). Results: A total of 9781 patients were included: 4598 with NSTEMI (28% women) and 5183 with STEMI (23% women). Discriminative capacity of the GRACE score was significantly lower in women with STEMI compared to men (area under the receiver operating characteristic curve [AUC] 0.82, 95% CI 0.78-0.86 vs. AUC 0.90, 95% CI 0.88-0.92, p = 0.0006). In multivariate analysis, female sex predicted hospital mortality independently of GRACE in STEMI (p = 0.019) but not in NSTEMI (p = 0.356) (interaction p = 0.0308). However, neither the AUC nor the net reclassification index (NRI) improved by including female sex in the STEMI subpopulation (NRI 0.0011, 95% CI -0.023 to 0.025; p = 0.928). Conclusions: Although female sex was an independent predictor of hospital mortality in the STEMI subpopulation, it does not substantially improve the discriminative ability of GRACE score.

Accuracy of Lung Ultrasonography in the Diagnosis of Pneumonia in Adults: Systematic Review and Meta-Analysis.

BACKGROUND: Some studies suggest that lung ultrasonography could be useful for diagnosing pneumonia; moreover, it has a more favorable safety profile and lower cost than chest radiography and CT. The aim of this study was to assess the accuracy of bedside lung ultrasonography for diagnosing pneumonia in adults through a systematic review and meta-analysis. METHODS: We searched MEDLINE, Scopus, The Cochrane Library, Web of Science, DARE, HTA Database, Google Scholar, LILACS, ClinicalTrials.gov, TESEO, and OpenGrey. In addition, we reviewed the bibliographies of relevant studies. Two researchers independently selected studies that met the inclusion criteria. Quality of the studies was assessed in accordance with the Quality Assessment of Diagnostic Accuracy Studies tool. The summary receiver operating characteristic (SROC) curve and a pooled estimation of the diagnostic odds ratio (DOR) was estimated using a bivariate random-effects analysis. The sources of heterogeneity were explored using predefined subgroup analyses and bivariate meta-regression. RESULTS: Sixteen studies (2,359 participants) were included. There was significant heterogeneity of both sensitivity and specificity according to the Q test, without clear evidence of threshold effect. The area under the SROC curve was 0.93, with a DOR at the optimal cutpoint of 50 (95% CI, 21-120). A tendency toward a higher area under the SROC curve in high-quality studies was detected; however, these differences were not significant after applying the bivariate meta-regression. CONCLUSIONS: Lung ultrasonography can help accurately diagnose pneumonia, and it may be promising as an adjuvant resource to traditional approaches.

Accessibility to Reperfusion Therapy Among Women with Acute Myocardial Infarction: Impact on Hospital Mortality.

BACKGROUND: The available evidence about the effect of gender and/or sex on mortality differences is contradictory. Our aim is to assess the impact of gender on the access to reperfusion therapy in patients with acute coronary syndrome with ST-segment elevation (STEMI), and secondly, to analyze the effect of delay on the differences with regard to hospital mortality. METHODS: A retrospective cohort study was conducted among consecutive patients with STEMI included in the ARIAM-SEMICYUC registry (2010-2013). RESULTS: A total of 4816 patients were included (22.09% women). Women were older, presented with longer patient delay (90 vs. 75 minutes, p=0.0066), higher risk profile (GRACE>140: 75.1% vs. 56.05%, p<0.0001), and received less reperfusion therapy (68.8% vs. 74.7%, p<0.0001) with longer total reperfusion time (307 vs. 240 minutes, p<0.0001). Women received less thrombolysis (24.53% vs. 29.98%, p<0.0001) and longer door-to-needle time (85 vs. 70 minutes, p 0.0023). We found no differences regarding primary percutaneous coronary intervention or door-to-balloon time. Women also had higher hospital mortality (crude odds ratio 2.54, 95% confidence interval 1.99-3.26, p<0.0001), which persisted after controlling the effect of patient delay, age, risk (GRACE), and reperfusion (adjusted odds ratio 1.43, 95% confidence interval 1.0-2.06, p=0.0492). Using TIMI or Killip risk scores as risk estimates yielded nonsignificant results. CONCLUSIONS: Compared with men, women with STEMI have worse access to reperfusion and higher hospital mortality. The impact of the differences in accessibility on mortality gap remains uncertain.

[Early invasive strategy in diabetic patients with non-ST-segment elevation acute coronary syndromes]. / Uso de estrategia invasiva precoz en pacientes diabéticos con síndrome coronario agudo sin elevación del ST.

BACKGROUND AND OBJECTIVES: In the management of non-ST-segment elevation acute coronary syndromes (NSTE-ACS), several studies have shown a reduction in mortality with the use of an invasive strategy in high-risk patients, including diabetic patients. Paradoxically, other studies have shown an under-utilization of this invasive strategy in these patients. The aim of this study is to determine the characteristics of patients managed conservatively and identify determinants of the use of invasive or conservative strategy. PATIENTS AND METHODS: Retrospective cohort study conducted in diabetic patients with NSTE-ACS included in the ARIAM-SEMICYUC registry (n=531) in 2010 and 2011. We performed crude and adjusted unconditional logistic regression. RESULTS: We analyzed 531 diabetic patients, 264 (49.7%) of which received invasive strategy. Patients managed conservatively were a subgroup characterized by older age and cardiovascular comorbidity, increased risk of bleeding and the absence of high-risk electrocardiogram (ECG). In diabetic patients with NSTE-ACS, independent predictors associated with conservative strategy were low-risk ECG, initial Killip class>1, high risk of bleeding and pretreatment with clopidogrel. CONCLUSIONS: The fear of bleeding complications or advanced coronary lesions could be the cause of the underutilization of an invasive strategy in diabetic patients with NSTE-ACS.

Clinical presentation of acute coronary syndrome in patients previously treated with nitrates.

AIMS: Several reports have suggested that nitrates limit acute ischaemic damage by a mechanism similar to preconditioning. This study aims to evaluate the effect of chronic oral nitrates on the clinical presentation and short-term outcomes of patients admitted with acute coronary syndrome (ACS). METHODS: A retrospective cohort study was conducted in patients with ACS admitted to 62 acute care units from 2010 to 2011. A propensity score-matched samples analysis was performed. RESULTS: We analysed 3171 consecutive patients, of whom 298 (9.4%) were chronically treated with nitrates. Patients previously treated with nitrates had higher comorbidity and disease severity at admission, lower prevalence of ACS with ST elevation, lower troponin elevation, higher prevalence of initial Killip class 2-4 and higher hospital mortality. The propensity score-matched analysis confirmed that previous use of nitrates is independently associated with a lower prevalence of ST-elevation ACS [odds ratio (OR) 0.53, 95% confidence interval (CI) 0.36-0.78; P = 0.0014] and a lower troponin elevation (OR 0.61, 95% CI 0.41-0.92) but not with Killip class on admission (OR 1.18, 95% CI 0.83-1.67, P = 0.3697) or mortality (OR 0.71, 95% CI 0.37-1.38, P = 0.3196). CONCLUSION: The results support the hypothesis that nitrates have a protective effect on acute ischaemic injury.

Cost effectiveness of anticoagulation in acute coronary syndromes.

BACKGROUND: The benefit of unfractionated heparin (UFH) added to aspirin in patients with acute coronary syndromes (ACS) was described more than 20 years ago. Ever since, a wide variety of anticoagulant drugs have become available for clinical use, including low-molecular-weight heparins (LMWH), direct thrombin inhibitors and selective factor Xa inhibitors. OBJECTIVE: The aim of this study was to critically review the available evidence on the cost and incremental cost effectiveness of anticoagulants in patients with ACS. METHODS: Studies were identified using specialist databases (UK NHS Economic Evaluation Database [NHS EED] and Cost-Effectiveness Analysis [CEA] Registry), PubMed and the reference lists of recovered articles. Only studies based on randomized controlled trials were considered for inclusion. Finally, 22 studies were included in the review. RESULTS: Enoxaparin is the only LMWH that has been shown to reduce the risk of death or myocardial infarction in patients with non-ST-elevation ACS (NSTE-ACS). In economic studies based on the ESSENCE trial conducted in the late 1990s, enoxaparin was consistently associated with a lower risk of coronary events, a reduction in the number of revascularization procedures and a lower cost per patient than UFH. However, these results refer to patients managed conservatively, with little use of thienopyridines and glycoprotein IIb/IIIa inhibitors, and the results are difficult to extrapolate to moderate-to-high-risk patients managed with the present day early invasive strategy. Available studies of LMWH in ACS with persistent elevation of ST-segment (STE-ACS) are limited to patients treated with thrombolysis. In this scenario, enoxaparin was shown to be a dominant alternative compared with UFH in a study based on the ASSENT-3 study and was considered an economically attractive alternative in three studies based on the ExTRACT-TIMI 25 study. However, these results should be interpreted cautiously due to the heterogeneity of the supportive randomized trials and the possible underestimation of bleeding costs. The effectiveness and safety of bivalirudin, a direct thrombin inhibitor, were evaluated in the ACUITY study (NSTE-ACS patients managed invasively) and the HORIZONS-AMI study (STE acute myocardial infarction patients planned for primary percutaneous coronary intervention). Bivalirudin monotherapy was not inferior to heparin plus a glycoprotein IIb/IIIa inhibitor and reduced the risk of major bleeding. The economic evaluations based on these studies suggest that bivalirudin is an attractive alternative to heparin plus a glycoprotein-IIb/IIIa inhibitor. In the OASIS-5 trial, compared with enoxaparin, fondaparinux reduced the mortality in patients with NSTE-ACS, probably because of a reduced risk of bleeding. In three economic evaluations of fondaparinux versus enoxaparin based on this trial, fondaparinux was the dominant strategy in two of them, and still economically attractive in a third. Taken as a whole, the usefulness of economic studies of anticoagulants in patients with ACS is undermined by the quality of the evidence about their effectiveness and safety; the narrow spectrum of the analysed scenarios; the lack of economic evaluations based on systematic reviews; the limitations of sensitivity analyses reported by the available economic evaluations; and their substantial risk of commercial bias. CONCLUSIONS: The available studies suggest that enoxaparin is an economically attractive alternative compared with UFH in patients with NSTE-ACS treated conservatively and STE-ACS patients treated with thrombolysis. Bivalirudin in patients with ACS treated invasively is cost effective compared with heparin plus a glycoprotein IIb/IIIa inhibitor. In patients with NSTE-ACS, fondaparinux is cost effective compared with enoxaparin. The usefulness of these results for decision making in contemporary clinical practice is limited due to problems of internal and external validity.

Prinzmetal's angina in a patient with angiosarcoma of the right cardiac chambers.

Variant (Prinzmetal's) angina pectoris is a clinical syndrome characterized by the presence of angina at rest, coinciding with a transient ST-segment elevation. This syndrome is often caused by vasospasm, either on a normal coronary artery or at the site of a coronary atherosclerotic stenosis. We describe a classic case of variant angina associated with an angiosarcoma of the right heart chambers.

Diagnostic accuracy of sTREM-1 to identify infection in critically ill patients with systemic inflammatory response syndrome.

OBJECTIVES: To assess the accuracy of plasma levels of soluble Triggering Receptor Expressed on Myeloid cells (sTREM)-1 to diagnose infection in critical patients with systemic inflammatory response syndrome (SIRS). DESIGN AND METHODS: We prospectively studied 114 patients with SIRS criteria. The patients' plasma levels of sTREM-1 were measured within 24h of admission to the intensive care unit. The final diagnosis of infection was made independently by two investigators, who were blinded to the levels of sTREM-1. RESULTS: The area under the ROC curve of sTREM-1 for the diagnosis of sepsis was 0.62 (95% confidence interval [95% CI] 0.51-0.72). The diagnostic odds ratio of sTREM-1 after adjusting for the Infection Probability Score and procalcitonin plasma levels was 1.81 (95% CI 0.66-4.98; p=0.2508). CONCLUSIONS: In critical patients admitted with SIRS, sTREM-1 has poor discriminative power to identify patients with infection, and sTREM-1 levels do not add diagnostic information to that provided by other routinely available clinical tests.

Cost effectiveness of fondaparinux in non-ST-elevation acute coronary syndrome.

BACKGROUND: Fondaparinux has been shown to reduce the risk of major bleeding and 30-day mortality compared with enoxaparin, in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). However, its cost effectiveness is not well known. OBJECTIVE: To evaluate the effectiveness and economic attractiveness of fondaparinux relative to enoxaparin in patients with NSTE-ACS treated with triple antiplatelet therapy and early (non-urgent) invasive strategy. METHODS: The decision model compares two alternative strategies: subcutaneous (SC) enoxaparin (1 mg/kg 12 hourly) versus SC fondaparinux (2.5 mg/day) in NSTE-ACS patients pre-treated with triple antiplatelet therapy and early revascularization. Cost-effectiveness and cost-utility analyses were performed from a healthcare perspective, based on a Markov model with a time horizon of the patient lifespan. Univariate sensitivity analysis and probabilistic (Monte Carlo) microsimulation analysis were performed. RESULTS: In the base-case analysis (65 years, Thrombolysis In Myocardial Infarction [TIMI] score 4), the use of fondaparinux was associated with a significant reduction in major bleeding, a slight reduction in adverse cardiac events, and minor improvements in survival and QALYs, together with a small reduction in costs. The dominance of fondaparinux over enoxaparin remained unchanged in the univariate sensitivity analyses. According to Monte Carlo simulation, fondaparinux was cost saving in 99.9% of cases. CONCLUSION: Compared with enoxaparin, the use of fondaparinux in patients with NSTE-ACS managed with an early invasive strategy appears to be cost effective, even in patients with a low risk of bleeding.

Cuff-leak test for the diagnosis of upper airway obstruction in adults: a systematic review and meta-analysis.

PURPOSE: To evaluate, in adults, the diagnostic accuracy of the cuff-leak test for the diagnosis of upper airway obstruction secondary to laryngeal edema and for reintubation secondary to upper airway obstruction. METHODS: Systematic review without language restrictions based on electronic databases and manual review of the literature up to December 2008. When appropriate, a random-effects meta-analysis and meta-regression (Moses' method) were performed. RESULTS: Upper airway obstruction was the outcome in nine studies with an overall incidence of 6.9%. There was significant heterogeneity among studies. The pooled sensitivity was 0.56 (95% confidence interval: 0.48-0.63), the specificity was 0.92 (95% CI: 0.90-0.93), the positive likelihood ratio was 5.90 (95% CI: 4.00-8.69), the negative likelihood ratio was 0.48 (95% CI: 0.33-0.72), and the diagnostic odds ratio was 18.78 (95% CI: 7.36-47.92). The area under the curve of the summary receiver-operator characteristic (SROC) was 0.92 (95% CI: 0.89-0.94). Only three studies have evaluated the accuracy of the cuff-leak test for reintubation secondary to upper airway obstruction. Overall incidence was 7%. The pooled sensitivity was 0.63 (95% CI: 0.38-0.84), the specificity was 0.86 (95% CI: 0.81-0.90), the positive likelihood ratio was 4.04 (95% CI: 2.21-7.40), the negative likelihood ratio was 0.46 (95% CI: 0.26-0.82), and the diagnostic odds ratio was 10.37 (95% CI: 3.70-29.13). CONCLUSIONS: A positive cuff-leak test (absence of leak) should alert the clinician of a high risk of upper airway obstruction.

Using triple antiplatelet therapy in patients with non-ST elevation acute coronary syndrome managed invasively: a cost-effectiveness analysis.

OBJECTIVES: To assess the incremental cost-effectiveness ratio (ICER) of glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitors in patients with non-ST elevation acute coronary syndrome (NSTE-ACS) pretreated with aspirin and clopidogrel undergoing an early invasive treatment strategy. METHODS: Cost-effectiveness analysis and cost-utility analysis were performed from a health-care system perspective, based on a Markov model with a time horizon of the patient life span. The risk of death and ischemic events was assessed using the Thrombolysis in Myocardial Infarction (TIMI) risk score. We compared three strategies: 1) routine upstream use of a GPIIb/IIIa inhibitor to all patients before angiography, 2) deferred selective use of abciximab in the catheterization laboratory just before angioplasty, and 3) double antiplatelet therapy without GPIIb/IIIa inhibitors. Both univariate sensitivity analysis and second-order probabilistic microsimulation were performed. RESULTS: In the base case (65 years old, TIMI score 3), strategy A was the most effective, with an ICER of 15,150 euros per quality-adjusted life-year gained. Strategy B was dominated by a combination of strategies A and C. The ICER was very sensitive to the age and baseline risk of the patient. According to the widely accepted cost-effectiveness thresholds, strategy A would be cost-effective only in patients with an intermediate to high TIMI score, especially within the younger age groups. The probability that strategy A was cost-effective under the base case was 91.2%. CONCLUSIONS: The use of GPIIb/IIIa inhibitors upstream in high-risk NSTE-ACS patients (TIMI score > or = 3) pretreated with aspirin and clopidogrel is cost-effective, particularly in the younger age groups.

Accuracy of B-type natriuretic peptide levels in the diagnosis of left ventricular dysfunction and heart failure: a systematic review.

OBJECTIVES: To evaluate the accuracy of B-type natriuretic peptide levels (BNP) in the diagnosis of heart failure and left ventricular dysfunction. DATA SOURCES: Electronic search in Medline, Embase, Cochrane Library and Medion database, and hand search of reference lists. REVIEW METHODS: We have included published studies on the accuracy of BNP which had both sufficient information to construct the 2x2 diagnostic cross table and an appropriate spectrum of patients. RESULTS: Fifty five studies (16,730 patients) were analyzed. The main determinants of diagnostic accuracy were the reference standard analyzed (clinical heart failure versus left ventricular dysfunction), and the methodological quality of the study. BNP levels were highly accurate for the diagnosis of clinical heart failure (diagnostic OR=41; 95% CI 23-74). The negative likelihood ratios were homogeneous, and useful for excluding the existence of heart failure (pooled negative likelihood ratio=0.11; 95% CI 0.08-0.16). The studies focused on the identification of left ventricular dysfunction were heterogeneous, with indications of publication bias, and showed less overall diagnostic accuracy than studies focused on heart failure. CONCLUSIONS: BNP levels are useful for ruling out heart failure. The accuracy of BNP for identifying patients with systolic dysfunction is more limited.

Using clopidogrel in non-ST-segment elevation acute coronary syndrome patients: a cost-utility analysis in Spain.

OBJECTIVE: The objective of this study was to estimate the cost-effectiveness of clopidogrel, administered for 1 year after hospital admission for non-ST-segment elevation acute coronary syndrome in the Spanish public health network. METHODS: A cost-utility analysis was conducted from the societal perspective. A Markov decision tree was constructed for modeling the long-term cardiovascular events according to the probabilities of the CURE study, the Framingham study, and the Spanish age-sex-specific mortality rates. The costs of the therapy were calculated mainly using the cost per diagnosis-related group in the Spanish National Health System. The utilities of the various states were estimated using data from published studies. A 3% discount rate was used for both the costs and the utilities. An expected value sensitivity analysis and a Monte Carlo microsimulation probabilistic analysis were performed. RESULTS: The cost per quality-adjusted life-year (QALY) saved owing to clopidogrel in the base case was about Euros 12000. This expected cost-effectiveness ratio was very sensitive to the age of the patient, the base risk of cardiovascular events, and the precision of the estimated effectiveness of clopidogrel. The cost per QALY ranged between some Euros 5000 for a high-risk, 40-year-old patient and Euros 30000 for a low-risk, 80-year-old patient. According to the accepted threshold for Spanish society, the probability that clopidogrel was cost-effective in the base analysis case was 85.3%. CONCLUSIONS: By Spanish standards, the use of clopidogrel in patients with non-ST-segment elevation acute coronary syndrome is cost-effective, at least when used for patients at high risk of presenting cardiovascular events.