Biomarkers of fever: from bench to bedside

__Abstract__ This thesis aims to study biomarkers in inflammation and infection, with a special focus on the distinction between infectious and non-infectious fever. The thesis consists of three parts, part I being this introduction, in which the concept of fever in infectious and non-infectious disease is discussed. Furthermore, in this part we provide an overview of the epidemiology of febrile disease, as studied both in a general hospital in the Netherlands and in a general hospital in Curaçao. Also, a review of current literature on biological markers in non-infectious fever is given. Part II describes our clinical studies with focus on biomarkers in different cohorts of patients with infectious and non-infectious fever. In part III, we summarize the findings of this thesis and discuss future research

Epidemiology of febrile diseases in the emergency department of a Caribbean Island: The Curaçao experience

Objective: The aetiology of febrile diseases in tropical countries often remains poorly characterized. We aim to describe the aetiology and outcome of febrile illnesses at the Emergency Department (ED) in Curaçao. Methods: From April 2008 - April 2009, all adult febrile patients (T > 38.5 oC) at the ED of the St Elisabeth Hospital, Curaçao, Netherlands Antilles, were included. Clinical data were recorded, routine laboratory measurements and blood cultures were taken. Final diagnoses were made at discharge by an independent physician and in retrospect by the main investigator. Results: Four hundred and three patients were included: 223 patients (55.6%) were hospitalized, 32 patients (7.9%) died and 18 patients (4.5%) were admitted to the Intensive Care Unit. In 129 febrile patients (32.0%), infection was proven; 84.4% of patients had bacterial (29.0% urinary tract infection, 23.2% pneumonia infection), 5.6% viral and 10.0% parasitic or fungal infections. Twenty-one patients (5.2%) were discharged with a non-infectious diagnosis and 172 patients (42.7%) without a clear diagnosis. Conclusion: A high mortality rate of 7.9% was observed. We found a high prevalence of bacterial infections, with pneumonia and urinary tract infections as the most common causes of fever. One in 20 patients did not have an infectious disease

Transforming care through bedside leader rounding: Use of handheld technology leads to improvement in perceived patient satisfaction

When consistently executed, leader rounding has the ability to capture actionable information ensuring delivery of safe and effective patient care, identifying excellence among staff, and bringing opportunities for improvement. Our team set out to create an effective, standardized approach to targeted, daily, technology-driven leader rounding with the goal of integrating real-time patient feedback into the care experience. An application on handheld computer tablets was tailored and integrated with the hospital’s admission, discharge, and transfer (ADT) feed, allowing for streamlining of the rounding process by creation of workflow templates. Additionally, capabilities to receive and send alerts across disciplines were integrated in order to respond to patient concerns in real-time. Patients who perceived they were rounded on had 3.53 greater odds of reporting top box scores for Overall Rating of Care compared to patients who perceived they were not rounded on (p\u3c0.001). Patients with documentation that rounding occurred, who also self-reported that rounding occurred, were at 3.43 greater odds of providing a top-box score than patients with documentation that rounding occurred but who did not perceive they were rounded on (p\u3c0.001). Efforts to round and to ensure patients know they are being rounded on may lead to improved patient experience

Reactive Jumps Preserve Skeletal Muscle Structure, Phenotype, and Myofiber Oxidative Capacity in Bed Rest

© Copyright © 2020 Blottner, Hastermann, Weber, Lenz, Gambara, Limper, Rittweger, Bosutti, Degens and Salanova. Identification of countermeasures able to prevent disuse-induced muscle wasting is crucial to increase performance of crew members during space flight as well as ameliorate patient’s clinical outcome after long immobilization periods. We report on the outcome of short but high-impact reactive jumps (JUMP) as countermeasure during 60 days of 6° head-down tilt (HDT) bed rest on myofiber size, type composition, capillarization, and oxidative capacity in tissue biopsies (pre/post/recovery) from the knee extensor vastus lateralis (VL) and deep calf soleus (SOL) muscle of 22 healthy male participants (Reactive jumps in a sledge, RSL-study 2015–2016, DLR:envihab, Cologne). Bed rest induced a slow-to-fast myofiber shift (type I –>II) with an increased prevalence of hybrid fibers in SOL after bed rest without jumps (control, CTRL, p = 0.016). In SOL, JUMP countermeasure in bed rest prevented both fast and slow myofiber cross-sectional area (CSA) decrements (p = 0.005) in CTRL group. In VL, bed rest only induced capillary rarefaction, as reflected by the decrease in local capillary-to-fiber ratio (LCFR) for both type II (pre vs. post/R + 10, p = 0.028/0.028) and type I myofibers (pre vs. R + 10, p = 0.012), which was not seen in the JUMP group. VO2maxFiber (pL × mm–1 × min–1) calculated from succinate dehydrogenase (SDH)-stained cryosections (OD660 nm) showed no significant differences between groups. High-impact jump training in bed rest did not prevent disuse-induced myofiber atrophy in VL, mitigated phenotype transition (type I – >II) in SOL, and attenuated capillary rarefaction in the prime knee extensor VL however with little impact on oxidative capacity changes

Procalcitonin as a potent marker of bacterial infection in febrile Afro-Caribbean patients at the emergency department

Procalcitonin (PCT) has been shown to be of additional value in the work-up of a febrile patient. This study is the first to investigate the additional value of PCT in an Afro-Caribbean febrile population at the emergency department (ED) of a general hospital. Febrile patients were included at the ED. Prospective, blinded PCT measurements were performed in patients with a microbiologically or serologically confirmed diagnosis or a strongly suspected diagnosis on clinical grounds. PCT analysis was performed in 93 patients. PCT levels differentiated well between confirmed bacterial and confirmed viral infection (area under the curve [AUC] of 0.82, sensitivity 85%, specificity 69%, cut-off 0.24 ng/mL), between confirmed bacterial infection and non-infectious fever (AUC of 0.84, sensitivity 90%, specificity 71%, cut-off 0.21 ng/mL) and between all bacterial infections (confirmed and suspected) and non-infectious fever (AUC of 0.80, sensitivity 85%, specificity 71%, cut-off 0.21 ng/mL). C-reactive protein (CRP) levels were shown to be less accurate when comparing the same groups. This is the first study showing that, in a non-Caucasian febrile population at the ED, PCT is a more valuable marker of bacterial infection than CRP. These results may improve diagnostics and eventually decrease antibiotic prescriptions in resource-limited settings

Higher diagnostic accuracy and cost-effectiveness using procalcitonin in the treatment of emergency medicine patients with fever (The HiTEMP study)

__Background:__ Fever is a common symptom in the emergency department(ED). Fever can be caused by bacterial infections, which are treated with antibiotics. Often, bacterial infections cannot be ruled out in the ED using standard diagnostics, and empiric antibiotic treatment is started. Procalcitonin(PCT) is a biomarker for bacterial infections, but its role in an undifferentiated ED population remains unclear. We hypothesize that PCT-guided therapy may reduce antibiotics prescription in undifferentiated febrile ED patients. The primary objectives of this study are to determine a) the efficacy, b) the safety of PCT-guided therapy, and c) the accuracy of the biomarker PCT for bacterial infections. The secondary objective is to study the cost-effectiveness of PCT-guided therapy. __Methods/design:__ This is a multicenter noninferiority randomized controlled trial. All adult ED patients with fever(≥38.2 °C) are randomized between standard care with and without the addition of a PCT level, after written informed consent. a) For efficacy, the reduction of patients receiving antibiotics is calculated, using a superiority analysis: differences between the PCT-guided group and control group are assessed using a Fisher's exact test, and a multivariable logistic regression analysis to account for the effects of demographic and medical variables on the percentage of febrile patients receiving antibiotics. b) Safety consists of a composite endpoint, defined as mortality, intensive care admission and ED return visit within 14 days. Noninferiority of PCT will be tested using a one-sided 95 % confidence interval for the difference in the composite safety endpoint between the PCT-guided and control groups using a noninferiority margin of 7.5 %. c) Accuracy of PCT and CRP for the diagnosis of bacterial infections will be reported, using the sensitivity, specificity, and the area under the receiver-operating-characteristic curve in the definitive diagnosis of bacterial infections. The sample size is 550 patients, which was calculated using a power analysis for all primary objectives. Enrollment of patients started in August 2014 and will last 2 years. __Discussion:__ PCT may offer a more tailor-made treatment to the individual ED patient with fever. Prospective costs analyses will reveal the economic consequences of implementing PCT-guided therapy in the ED. This trial is registered in the Dutch trial register:NTR4949