A European research agenda for somatic symptom disorders, bodily distress disorders, and functional disorders: Results of an estimate-talk-estimate delphi expert study

Background: Somatic Symptom Disorders (SSD), Bodily Distress Disorders (BDD) and functional disorders (FD) are associated with high medical and societal costs and pose a substantial challenge to the population and health policy of Europe. To meet this challenge, a specific research agenda is needed as one of the cornerstones of sustainable mental health research and health policy for SSD, BDD, and FD in Europe. Aim: To identify the main challenges and research priorities concerning SSD, BDD, and FD from a European perspective. Methods: Delphi study conducted from July 2016 until October 2017 in 3 rounds with 3 workshop meetings and 3 online surveys, involving 75 experts and 21 European countries. EURONET-SOMA and the European Association of Psychosomatic Medicine (EAPM) hosted the meetings. Results: Eight research priorities were identified: (1) Assessment of diagnostic profiles relevant to course and treatment outcome. (2) Development and evaluation of new, effective interventions. (3) Validation studies on questionnaires or semi-structured interviews that assess chronic medical conditions in this context. (4) Research into patients preferences for diagnosis and treatment. (5) Development of new methodologic designs to identify and explore mediators and moderators of clinical course and treatment outcomes (6). Translational research exploring how psychological and somatic symptoms develop from somatic conditions and biological and behavioral pathogenic factors. (7) Development of new, effective interventions to personalize treatment. (8) Implementation studies of treatment interventions in different settings, such as primary care, occupational care, general hospital and specialty mental health settings. The general public and policymakers will benefit from the development of new, effective, personalized interventions for SSD, BDD, and FD, that will be enhanced by translational research, as well as from the outcomes of research into patient involvement, GP-patient communication, consultation-liaison models and implementation. Conclusion: Funding for this research agenda, targeting these challenges in coordinated research networks such as EURONET-SOMA and EAPM, and systematically allocating resources by policymakers to this critical area in mental and physical well-being is urgently needed to improve efficacy and impact for diagnosis and treatment of SSD, BDD, and FD across Europe

Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DALI) cohort

Objectives:We utilized the database of the Defining Antibiotic Levels in Intensive care unit patients (DALI) study to statistically compare the pharmacokinetic/pharmacodynamic and clinical outcomes between prolonged-infusion and intermittent-bolus dosing of piperacillin/tazobactam and meropenem in critically ill patients using inclusion criteria similar to those used in previous prospective studies.Methods: This was a post hoc analysis of a prospective, multicentre pharmacokinetic point-prevalence study (DALI), which recruited a large cohort of critically ill patients from 68 ICUs across 10 countries.Results: Of the 211 patients receiving piperacillin/tazobactam and meropenem in the DALI study, 182 met inclusion criteria. Overall, 89.0% (162/182) of patients achieved the most conservative target of 50% fT(> MIC) (time over which unbound or free drug concentration remains above the MIC). Decreasing creatinine clearance and the use of prolonged infusion significantly increased the PTA for most pharmacokinetic/pharmacodynamic targets. In the subgroup of patients who had respiratory infection, patients receiving beta-lactams via prolonged infusion demonstrated significantly better 30 day survival when compared with intermittent-bolus patients [86.2% (25/29) versus 56.7% (17/30); P=0.012]. Additionally, in patients with a SOFA score of >= 9, administration by prolonged infusion compared with intermittent-bolus dosing demonstrated significantly better clinical cure [73.3% (11/15) versus 35.0% (7/20); P=0.035] and survival rates [73.3% (11/15) versus 25.0% (5/20); P=0.025].Conclusions: Analysis of this large dataset has provided additional data on the niche benefits of administration of piperacillin/tazobactam and meropenem by prolonged infusion in critically ill patients, particularly for patients with respiratory infections

Intraoperative transfusion practices in Europe

BACKGROUND: Transfusion of allogeneic blood influences outcome after surgery. Despite widespread availability of transfusion guidelines, transfusion practices might vary among physicians, departments, hospitals and countries. Our aim was to determine the amount of packed red blood cells (pRBC) and blood products transfused intraoperatively, and to describe factors determining transfusion throughout Europe. METHODS: We did a prospective observational cohort study enrolling 5803 patients in 126 European centres that received at least one pRBC unit intraoperatively, during a continuous three month period in 2013. RESULTS: The overall intraoperative transfusion rate was 1.8%; 59% of transfusions were at least partially initiated as a result of a physiological transfusion trigger- mostly because of hypotension (55.4%) and/or tachycardia (30.7%). Haemoglobin (Hb)- based transfusion trigger alone initiated only 8.5% of transfusions. The Hb concentration [mean (sd)] just before transfusion was 8.1 (1.7) g dl(-1) and increased to 9.8 (1.8) g dl(-1) after transfusion. The mean number of intraoperatively transfused pRBC units was 2.5 (2.7) units (median 2). CONCLUSION: Although European Society of Anaesthesiology transfusion guidelines are moderately implemented in Europe with respect to Hb threshold for transfusion (7-9 g dl(-1)), there is still an urgent need for further educational efforts that focus on the number of pRBC units to be transfused at this threshold. CLINICAL TRIAL REGISTRATION: NCT 01604083

Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DALI) cohort

Objectives: We utilized the database of the Defining Antibiotic Levels in Intensive care unit patients (DALI) study to statistically compare the pharmacokinetic/pharmacodynamic and clinical outcomes between prolonged- infusion and intermittent-bolus dosing of piperacillin/tazobactam and meropenem in critically ill patients using inclusion criteria similar to those used in previous prospective studies. Methods: This was a post hoc analysis of a prospective, multicentre pharmacokinetic point-prevalence study (DALI), which recruited a large cohort of critically ill patients from 68 ICUs across 10 countries. Results: Of the 211 patients receiving piperacillin/tazobactam and meropenem in the DALI study, 182 met inclusion criteria. Overall, 89.0% (162/182) of patients achieved the most conservative target of 50% fT 65MIC (time over which unbound or free drug concentration remains above the MIC). Decreasing creatinine clearance and the use of prolonged infusion significantly increased the PTA for most pharmacokinetic/pharmacodynamic targets. In the subgroup of patients who had respiratory infection, patients receiving \u3b2-lactams via prolonged infusion demonstrated significantly better 30 day survival when compared with intermittent-bolus patients [86.2% (25/29) versus 56.7% (17/30); P=0.012]. Additionally, in patients with a SOFA score of 65 9, administration by prolonged infusion compared with intermittent-bolus dosing demonstrated significantly better clinical cure [73.3% (11/15) versus 35.0% (7/20); P=0.035] and survival rates [73.3% (11/15) versus 25.0% (5/20); P=0.025]. Conclusions: Analysis of this large dataset has provided additional data on the niche benefits of administration of piperacillin/tazobactam and meropenem by prolonged infusion in critically ill patients, particularly for patients with respiratory infections. \ua9 The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved

DALI: Defining antibiotic levels in intensive care unit patients: Are current ß-lactam antibiotic doses sufficient for critically ill patients?

Background. Morbidity and mortality for critically ill patients with infections remains a global healthcare problem. We aimed to determine whether α-lactam antibiotic dosing in critically ill patients achieves concentrations associated with maximal activity and whether antibiotic concentrations affect patient outcome.Methods. This was a prospective, multinational pharmacokinetic point-prevalence study including 8 α-lactam antibiotics. Two blood samples were taken from each patient during a single dosing interval. The primary pharmacokinetic/pharmacodynamic targets were free antibiotic concentrations above the minimum inhibitory concentration (MIC) of the pathogen at both 50% (50% f TMIC) and 100% (100% f T MIC) of the dosing interval. We used skewed logistic regression to describe the effect of antibiotic exposure on patient outcome.Results. We included 384 patients (361 evaluable patients) across 68 hospitals. The median age was 61 (interquartile range [IQR], 48-73) years, the median Acute Physiology and Chronic Health Evaluation II score was 18 (IQR, 14-24), and 65% of patients were male. Of the 248 patients treated for infection, 16% did not achieve 50% f TMIC and these patients were 32% less likely to have a positive clinical outcome (odds ratio [OR], 0.68; P =. 009). Positive clinical outcome was associated with increasing 50% f TMIC and 100% f TMIC ratios (OR, 1.02 and 1.56, respectively; P <. 03), with significant interaction with sickness severity status.Conclusions. Infected critically ill patients may have adverse outcomes as a result of inadeqaute antibiotic exposure; a paradigm change to more personalized antibiotic dosing may be necessary to improve outcomes for these most seriously ill patients. © 2014 The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved

Dali: Defining Antibiotic Levels In Intensive Care Unit Patients: Are Current Beta-Lactam Antibiotic Doses Sufficient For Critically Ill Patients?

Background. Morbidity and mortality for critically ill patients with infections remains a global healthcare problem. We aimed to determine whether beta-lactam antibiotic dosing in critically ill patients achieves concentrations associated with maximal activity and whether antibiotic concentrations affect patient outcome. Methods. This was a prospective, multinational pharmacokinetic point-prevalence study including 8 beta-lactam antibiotics. Two blood samples were taken from each patient during a single dosing interval. The primary pharmacokinetic/pharmacodynamic targets were free antibiotic concentrations above the minimum inhibitory concentration (MIC) of the pathogen at both 50% (50% sic T-> MIC) and 100% (100% sic T > MIC) of the dosing interval. We used skewed logistic regression to describe the effect of antibiotic exposure on patient outcome. Results. We included 384 patients (361 evaluable patients) across 68 hospitals. The median age was 61 (interquartile range [IQR], 48-73) years, the median Acute Physiology and Chronic Health Evaluation II score was 18 (IQR, 14-24), and 65% of patients were male. Of the 248 patients treated for infection, 16% did not achieve 50% sic T-> MIC and these patients were 32% less likely to have a positive clinical outcome (odds ratio [OR], 0.68; P =.009). Positive clinical outcome was associated with increasing 50% sic T-> MIC and 100% sic T-> MIC ratios (OR, 1.02 and 1.56, respectively; P <.03), with significant interaction with sickness severity status. Conclusions. Infected critically ill patients may have adverse outcomes as a result of inadeqaute antibiotic exposure; a paradigm change to more personalized antibiotic dosing may be necessary to improve outcomes for these most seriously ill patients.WoSScopu