Nordic Economic Policy Review

The Nordic Economic Policy Review is published by the Nordic Council of Ministers. This year’s issue is part of the Danish presidency programme for the Nordic Council of Ministers in 2015. The review addresses policy issues in a way that is useful for in-formed non-specialists as well as for professional economists. All articles are commissioned from leading professional economists and are subject to peer review prior to publication. The review appears once a year. It is published electronically on the website of the Nordic Council of Ministers: www.norden.org/en. On that website, you can also order paper copies of the Review (enter the name of the Review in the search field, and you will find all the information you need)

MOESM1 of Prediction of non-recovery from ventilator-demanding acute respiratory failure, ARDS and death using lung damage biomarkers: data from a 1200-patient critical care randomized trial

Additional file 1. Death from all causes according to level of surfactant protein D. Y-axis is cummulative risk of death. Bold line is for patients with low surfactant protein D; stipulated line is for patients with high surfactant protein D. Grey areas are 95% confidence intervals

Predicting recovery from acute kidney injury in critically ill patients: development and validation of a prediction model.

To access publisher's full text version of this article click on the hyperlink belowIntensive care unit (ICU) patients with acute kidney injury (AKI) who recover kidney function within 28 days experience less severe chronic kidney impairment and have increased long term survival. The aims of this study were to develop and validate a risk prediction model to identify these patients.Observational study with development and validation of a risk prediction model.Nine academic ICUs in Denmark.Development cohort of critically ill patients with AKI at ICU admission from the Procalcitonin and Survival Study cohort (n = 568), validation cohort of adult patients with AKI admitted to two university hospitals in Denmark in 2012-13 (n = 766).None.Recovery of kidney function was defined as living for 5 consecutive days with no renal replacement therapy and with creatinine plasma levels below 1.5-fold the levels determined before ICU admission.A total of 266 patients (46.8%) recovered prior kidney function in the development cohort, and 453 patients (59.1%) in the validation cohort. The prediction model included elevation in creatinine, urinary output, sex and age. In the validation cohort, 69 patients (9.0%) had a predicted chance of recovery 75%. The area under the receiver operations curves for predicting recovery in the validation cohort was 73.1%.We constructed and validated a simple model that can predict the chance of recovery from AKI in critically ill patients.Danish National Research Foundation Centre of Excellence for Health, Immunity and Infections (CHIP) Centre of Excellence for Personalised Medicine of Infectious Complications in Immune Deficiency (PERSIMUNE) Lundbeck Foundation Research Foundation for the Capital Region of Denmark Toyota Foundation Brahms Diagnostica Harboe Foundation AP Moller Foundation Fru Olga Brydes Nielsens Foundation Research Board at NordsjIlands Hospita

Predicting recovery from acute kidney injury in critically ill patients: development and validation of a prediction model.

To access publisher's full text version of this article click on the hyperlink belowIntensive care unit (ICU) patients with acute kidney injury (AKI) who recover kidney function within 28 days experience less severe chronic kidney impairment and have increased long term survival. The aims of this study were to develop and validate a risk prediction model to identify these patients.Observational study with development and validation of a risk prediction model.Nine academic ICUs in Denmark.Development cohort of critically ill patients with AKI at ICU admission from the Procalcitonin and Survival Study cohort (n = 568), validation cohort of adult patients with AKI admitted to two university hospitals in Denmark in 2012-13 (n = 766).None.Recovery of kidney function was defined as living for 5 consecutive days with no renal replacement therapy and with creatinine plasma levels below 1.5-fold the levels determined before ICU admission.A total of 266 patients (46.8%) recovered prior kidney function in the development cohort, and 453 patients (59.1%) in the validation cohort. The prediction model included elevation in creatinine, urinary output, sex and age. In the validation cohort, 69 patients (9.0%) had a predicted chance of recovery 75%. The area under the receiver operations curves for predicting recovery in the validation cohort was 73.1%.We constructed and validated a simple model that can predict the chance of recovery from AKI in critically ill patients.Danish National Research Foundation Centre of Excellence for Health, Immunity and Infections (CHIP) Centre of Excellence for Personalised Medicine of Infectious Complications in Immune Deficiency (PERSIMUNE) Lundbeck Foundation Research Foundation for the Capital Region of Denmark Toyota Foundation Brahms Diagnostica Harboe Foundation AP Moller Foundation Fru Olga Brydes Nielsens Foundation Research Board at NordsjIlands Hospita

Prediction of non-recovery from ventilator-demanding acute respiratory failure, ARDS and death using lung damage biomarkers: data from a 1200-patient critical care randomized trial

Abstract Background It is unclear whether biomarkers of alveolar damage (surfactant protein D, SPD) or conductive airway damage (club cell secretory protein 16, CC16) measured early after intensive care admittance are associated with one-month clinical respiratory prognosis. If patients who do not recover respiratory function within one month can be identified early, future experimental lung interventions can be aimed toward this high-risk group. We aimed to determine, in a heterogenous critically ill population, whether baseline profound alveolar damage or conductive airway damage has clinical respiratory impact one month after intensive care admittance. Methods Biobank study of biomarkers of alveolar and conductive airway damage in intensive care patients was conducted. This was a sub-study of 758 intubated patients from a 1200-patient randomized trial. We split the cohort into a “learning cohort” and “validating cohort” based on geographical criteria: northern sites (learning) and southern sites (validating). Results Baseline SPD above the 85th percentile in the “learning cohort” predicted low chance of successful weaning from ventilator within 28 days (adjusted hazard ratio 0.6 [95% CI 0.4–0.9], p = 0.005); this was confirmed in the validating cohort. CC16 did not predict the endpoint. The absolute risk of not being successfully weaned within the first month was 48/106 (45.3%) vs. 175/652 (26.8%), p < 0.0001 (high SPD vs. low SPD). The chance of being “alive and without ventilator ≥20 days within the first month” was lower among patients with high SPD (adjusted OR 0.2 [95% CI 0.2–0.4], p < 0.0001), confirmed in the validating cohort, and the risk of ARDS was higher among patients with high SPD (adjusted OR 3.4 [95% CI 1.0–11.4], p = 0.04)—also confirmed in the validating cohort. Conclusion Early profound alveolar damage in intubated patients can be identified by SPD blood measurement at intensive care admission, and high SPD level is a strong independent predictor that the patient suffers from ARDS and will not recover independent respiratory function within one month. This knowledge can be used to improve diagnostic and prognostic models and to identify the patients who most likely will benefit from experimental interventions aiming to preserve alveolar tissue and therefore respiratory function. Trial registration This is a sub-study to the Procalcitonin And Survival Study (PASS), Clinicaltrials.gov ID: NCT00271752, first registered January 1, 200

The Potential of Antimicrobials to Induce Thrombocytopenia in Critically Ill Patients: Data from a Randomized Controlled Trial

<div><p>Background</p><p>Antimicrobial-induced thrombocytopenia is frequently described in the literature among critically ill patients. Several antimicrobials have been implicated, although experimental evidence to demonstrate causality is limited. We report, using a randomized trial, the potential of antimicrobials to induce thrombocytopenia.</p> <p>Methods</p><p>Randomized trial allocated patients to antimicrobial treatment according to standard- of-care (SOC group) or drug-escalation in case of procalcitonin increases (high-exposure group). Patients were followed until death or day 28. Thrombocytopenia defined as absolute (platelet count ≤100x109/L) or relative (≥20% decrease in platelet count). Analyses were performed in the two randomized groups and as a merged cohort. </p> <p>Results</p><p>Of the 1147 patients with platelet data available, 18% had absolute thrombocytopenia within the first 24 hours after admission to intensive care unit and additional 17% developed this complication during follow-up; 57% developed relative thrombocytopenia during follow-up. Absolute and relative thrombocytopenia day 1-4 was associated with increased mortality (HR: 1.67 [95% CI: 1.30 to 2.14]; 1.71 [95% CI: 1.30 to 2.30], P<0.0001, respectively). Patients in the high-exposure group received more antimicrobials including piperacillin/tazobactam, meropenem and ciprofloxacin compared with the SOC group, whereas cefuroxime was used more frequently in the SOC group (p<0.05). Risk of absolute and relative thrombocytopenia (RR: 0.9 [0.7-1.3], p=0.7439; 1.2 [1.0-1.4], p=0.06; respectively), as well as absolute platelet count (daily difference, high-exposure vs. SOC -1.7 [-3.8-0.5], p=0.14) was comparable between groups. In observational analyses, use of ciprofloxacin and piperacillin/tazobactam predicted risk of relative thrombocytopenia (vs. cefuroxime, RR: 2.08 [1.48-2.92]; 1.44 [1.10-1.89], respectively), however only ciprofloxacin were associated with a reduction in absolute platelet count (p=0.0005). </p> <p>Conclusion</p><p>High exposure to broad-spectrum antimicrobials does not result in a reduction in thrombocytopenia in critically ill patients. However, single use of ciprofloxacin, and less so piperacillin/tazobactam, may contribute to a lower platelet count.</p> <p>Trial Registration</p><p><a href="http://clinicaltrials.gov" target="_blank">ClinicalTrials.gov</a> NCT00271752 <a href="http://clinicaltrials.gov/ct2/show/nct00271752" target="_blank">http://clinicaltrials.gov/ct2/show/NCT00271752</a></p> </div

The Procalcitonin And Survival Study (PASS) – A Randomised multi-center investigator-initiated trial to investigate whether daily measurements biomarker <it>Procalcitonin </it>and pro-active diagnostic and therapeutic responses to abnormal Procalcitonin levels, can improve survival in intensive care unit patients. Calculated sample size (target population): 1000 patients

<p>Abstract</p> <p>Background</p> <p>Sepsis and complications to sepsis are major causes of mortality in critically ill patients. Rapid treatment of sepsis is of crucial importance for survival of patients. The infectious status of the critically ill patient is often difficult to assess because symptoms cannot be expressed and signs may present atypically. The established biological markers of inflammation (leucocytes, C-reactive protein) may often be influenced by other parameters than infection, and may be unacceptably slowly released after progression of an infection. At the same time, lack of a relevant antimicrobial therapy in an early course of infection may be fatal for the patient. Specific and rapid markers of bacterial infection have been sought for use in these patients.</p> <p>Methods</p> <p>Multi-centre randomized controlled interventional trial. Powered for superiority and non-inferiority on all measured end points. Complies with, "Good Clinical Practice" (ICH-GCP Guideline (CPMP/ICH/135/95, Directive 2001/20/EC)). Inclusion: 1) Age ≥ 18 years of age, 2) Admitted to the participating intensive care units, 3) Signed written informed consent.</p> <p>Exclusion: 1) Known hyper-bilirubinaemia. or hypertriglyceridaemia, 2) Likely that safety is compromised by blood sampling, 3) Pregnant or breast feeding.</p> <p>Computerized Randomisation: Two arms (1:1), n = 500 per arm: Arm 1: standard of care. Arm 2: standard of care and Procalcitonin guided diagnostics and treatment of infection.</p> <p>Primary Trial Objective: To address whether daily Procalcitonin measurements and immediate diagnostic and therapeutic response on day-to-day changes in procalcitonin can reduce the mortality of critically ill patients.</p> <p>Discussion</p> <p>For the first time ever, a mortality-endpoint, large scale randomized controlled trial with a biomarker-guided strategy compared to the best standard of care, is conducted in an Intensive care setting. Results will, with a high statistical power answer the question: Can the survival of critically ill patients be improved by actively using biomarker procalcitonin in the treatment of infections? 700 critically ill patients are currently included of 1000 planned (June 2008). Two interim analyses have been passed without any safety or futility issues, and the third interim analysis is soon to take place. Trial registration number at clinicaltrials.gov: Id. nr.: NCT00271752).</p