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Objectives: To evaluate the diagnostic performance of N-terminal pro-B-type natriuretic peptide (NT-proBNP) thresholds for acute heart failure and to develop and validate a decision support tool that combines NT-proBNP concentrations with clinical characteristics. Design: Individual patient level data meta-analysis and modelling study. Setting: Fourteen studies from 13 countries, including randomised controlled trials and prospective observational studies. Participants: Individual patient level data for 10 369 patients with suspected acute heart failure were pooled for the meta-analysis to evaluate NT-proBNP thresholds. A decision support tool (Collaboration for the Diagnosis and Evaluation of Heart Failure (CoDE-HF)) that combines NT-proBNP with clinical variables to report the probability of acute heart failure for an individual patient was developed and validated. Main outcome measure: Adjudicated diagnosis of acute heart failure. Results: Overall, 43.9% (4549/10 369) of patients had an adjudicated diagnosis of acute heart failure (73.3% (2286/3119) and 29.0% (1802/6208) in those with and without previous heart failure, respectively). The negative predictive value of the guideline recommended rule-out threshold of 300 pg/mL was 94.6% (95% confidence interval 91.9% to 96.4%); despite use of age specific rule-in thresholds, the positive predictive value varied at 61.0% (55.3% to 66.4%), 73.5% (62.3% to 82.3%), and 80.2% (70.9% to 87.1%), in patients aged [removed]75 years, respectively. Performance varied in most subgroups, particularly patients with obesity, renal impairment, or previous heart failure. CoDE-HF was well calibrated, with excellent discrimination in patients with and without previous heart failure (area under the receiver operator curve 0.846 (0.830 to 0.862) and 0.925 (0.919 to 0.932) and Brier scores of 0.130 and 0.099, respectively). In patients without previous heart failure, the diagnostic performance was consistent across all subgroups

Abstract:Objectives: To evaluate the diagnostic performance of N-terminal pro-B-type natriuretic peptide (NT-proBNP) thresholds for acute heart failure and to develop and validate a decision support tool that combines NT-proBNP concentrations with clinical characteristics. Design: Individual patient level data meta-analysis and modelling study. Setting: Fourteen studies from 13 countries, including randomised controlled trials and prospective observational studies. Participants: Individual patient level data for 10 369 patients with suspected acute heart failure were pooled for the meta-analysis to evaluate NT-proBNP thresholds. A decision support tool (Collaboration for the Diagnosis and Evaluation of Heart Failure (CoDE-HF)) that combines NT-proBNP with clinical variables to report the probability of acute heart failure for an individual patient was developed and validated. Main outcome measure: Adjudicated diagnosis of acute heart failure. Results: Overall, 43.9% (4549/10 369) of patients had an adjudicated diagnosis of acute heart failure (73.3% (2286/3119) and 29.0% (1802/6208) in those with and without previous heart failure, respectively). The negative predictive value of the guideline recommended rule-out threshold of 300 pg/mL was 94.6% (95% confidence interval 91.9% to 96.4%); despite use of age specific rule-in thresholds, the positive predictive value varied at 61.0% (55.3% to 66.4%), 73.5% (62.3% to 82.3%), and 80.2% (70.9% to 87.1%), in patients aged <50 years, 50-75 years, and >75 years, respectively. Performance varied in most subgroups, particularly patients with obesity, renal impairment, or previous heart failure. CoDE-HF was well calibrated, with excellent discrimination in patients with and without previous heart failure (area under the receiver operator curve 0.846 (0.830 to 0.862) and 0.925 (0.919 to 0.932) and Brier scores of 0.130 and 0.099, respectively). In patients without previous heart failure, the diagnostic performance was co

Aim: To determine whether initiation of antibiotic therapy (ABX) by procalcitonin (PCT) within 8 h of admission in patients presenting to the emergency department with symptoms and signs of acute heart failure (AHF) and elevated natriuretic peptides would improve clinical outcomes. Methods and results: The study was a randomized multicentre clinical trial conducted at 16 sites in Europe. Patients were randomized to either a PCT-guided strategy or standard care. Patients with PCT-guided strategy (n = 370) had ABX initiated if PCT was > 0.2 μg/L. Patients with standard care (n = 372) had AHF care in accordance with published guidelines without PCT. The primary endpoint was 90-day all-cause mortality. Pre-specified secondary endpoints included 30-day all-cause mortality and readmission and rate of pneumonia. The Data Safety and Review Committee recommended stopping the study for futility when 762 of the planned 792 patients had been enrolled. A total of 742 patients could be analysed. Patients were elderly (median age: 77 years), 38% were women, and had typical signs and symptoms of AHF. All-cause mortality at 90 days was 10.3% in the PCT-guided group vs. 8.2% in standard care (P = 0.316). Thirty-day readmission was significantly higher in the PCT-guided group vs. standard care but the difference vanished until day 90. The rate of pneumonia was overall low (7.5%) and not different between groups. Conclusions: In patients with AHF, a strategy of PCT-guided initiation of ABX was not more effective than a standard care strategy in improving clinical outcomes.

Background: In randomised controlled trials, procalcitonin (PCT)-guided antibiotic treatment has been proven to significantly reduce length of antibiotic therapy in intensive care unit (ICU) patients. However, concern was raised on low protocol adherence and high rates of overruling, and thus the value of PCT-guided treatment in real clinical life outside study conditions remains unclear. In this study, adherence to a PCT protocol to guide antibiotic treatment in patients with severe sepsis and septic shock was analysed. Methods: From 2012 to 2014, surgical ICU patients with severe sepsis or septic shock were retrospectively screened for PCT measurement series appropriate to make treatment decisions on antibiotic therapy We compared (1) patients with appropriate PCT measurement series to patients without appropriate series; (2) patients who reached the antibiotic stopping advice threshold (PCT < 0.5 ng/mL and/or decrease to 10% of peak level) to patients who did not reach a stopping advice threshold; and (3) patients who were treated adherently to the PCT protocol to non-adherently treated patients. The groups were compared in terms of antibiotic treatment duration, PCT kinetics, and other clinical outcomes. Results: Of 81 patients with severe sepsis or septic shock, 14 were excluded due to treatment restriction or short course in the ICU. The final analysis was performed on 67 patients Forty-two patients (62.7%) had appropriate PCT measurement series In patients with appropriate PCT series, median initial PCT (p = 0.001) and peak PCT levels (p < 0.001) were significantly higher compared to those with non-appropriate series. In 26 patients with appropriate series, PCT levels reached an antibiotic stopping advice. In 8 of 26 patients with stopping advice, antibiotics were discontinued adherently to the PCT protocol (30.8%). Patients with adherently discontinued antibiotics had a shorter antibiotic treatment (7d [IQR 6-9] vs. 12d [IQR 9-16]; p = 0. 002) No differences

Background: In randomised controlled trials, procalcitonin (PCT)-guided antibiotic treatment has been proven to significantly reduce length of antibiotic therapy in intensive care unit (ICU) patients. However, concern was raised on low protocol adherence and high rates of overruling, and thus the value of PCT-guided treatment in real clinical life outside study conditions remains unclear. In this study, adherence to a PCT protocol to guide antibiotic treatment in patients with severe sepsis and septic shock was analysed. Methods: From 2012 to 2014, surgical ICU patients with severe sepsis or septic shock were retrospectively screened for PCT measurement series appropriate to make treatment decisions on antibiotic therapy We compared (1) patients with appropriate PCT measurement series to patients without appropriate series; (2) patients who reached the antibiotic stopping advice threshold (PCT < 0.5 ng/mL and/or decrease to 10% of peak level) to patients who did not reach a stopping advice threshold; and (3) patients who were treated adherently to the PCT protocol to non-adherently treated patients. The groups were compared in terms of antibiotic treatment duration, PCT kinetics, and other clinical outcomes. Results: Of 81 patients with severe sepsis or septic shock, 14 were excluded due to treatment restriction or short course in the ICU. The final analysis was performed on 67 patients Forty-two patients (62.7%) had appropriate PCT measurement series In patients with appropriate PCT series, median initial PCT (p = 0.001) and peak PCT levels (p < 0.001) were significantly higher compared to those with non-appropriate series. In 26 patients with appropriate series, PCT levels reached an antibiotic stopping advice. In 8 of 26 patients with stopping advice, antibiotics were discontinued adherently to the PCT protocol (30.8%). Patients with adherently discontinued antibiotics had a shorter antibiotic treatment (7d [IQR 6-9] vs. 12d [IQR 9-16]; p = 0. 002) No differences

BACKGROUND Pneumonia is among the most common acute complications after stroke and is associated with poor long-term outcome. Biomarkers may help identifying stroke patients at high risk for developing stroke-associated pneumonia (SAP) and to guide early treatment. AIMS This trial investigated whether procalcitonin (PCT) ultrasensitive (PCTus)-guided antibiotic treatment of SAP can improve functional outcome after stroke. METHODS In this international, multicenter, randomized, controlled clinical trial with blinded assessment of outcomes, patients with severe ischemic stroke in the middle cerebral artery territory were randomly assigned within 40 h after symptom onset to PCTus-based antibiotic therapy guidance in addition to stroke unit care or standard stroke unit care alone. The primary endpoint was functional outcome at 3 months, defined according to the modified Rankin Scale (mRS) and dichotomized as acceptable (≤4) or unacceptable (≥5). Secondary endpoints included usage of antibiotics, infection rates, days of fever, and mortality. The trial was registered with http://ClinicalTrials.gov (Identifier NCT01264549). RESULTS In the intention-to-treat-analysis based on 227 patients (112 in PCT and 115 in control group), 197 patients completed the 3-month follow-up. Adherence to PCT guidance was 65%. PCT-guided therapy did not improve functional outcome as measured by mRS (odds ratio 0.79; 95% confidence interval 0.45-1.35, p = 0.47). Pneumonia rate and mortality were similar in both groups. Days with fever tended to be lower (p = 0.055), whereas total number of days treated with antibiotics were higher (p = 0.004) in PCT compared to control group. A post hoc analysis including all PCT values in the intention-to-treat population demonstrated a significant increase on the first day of infection in patients with pneumonia and sepsis compared to patients with urinary tract infections or without infections (p < 0.0001). CONCLUSION PCTus-guided antibiotic therapy did not