Which Biomarkers Can Be Used as Diagnostic Tools for Infection in Suspected Sepsis?

AbstractThe diagnosis of infection in patients with suspected sepsis is frequently difficult to achieve with a reasonable degree of certainty. Currently, the diagnosis of infection still relies on a combination of systemic manifestations, manifestations of organ dysfunction, and microbiological documentation. In addition, the microbiologic confirmation of infection is obtained only after 2 to 3 days of empiric antibiotic therapy. These criteria are far from perfect being at least in part responsible for the overuse and misuse of antibiotics, in the community and in hospital, and probably the main drive for antibiotic resistance. Biomarkers have been studied and used in several clinical settings as surrogate markers of infection to improve their diagnostic accuracy as well as in the assessment of response to antibiotics and in antibiotic stewardship programs. The aim of this review is to provide a clear overview of the current evidence of usefulness of biomarkers in several clinical scenarios, namely, to diagnose infection to prescribe antibiotics, to exclude infection to withhold antibiotics, and to identify the causative pathogen to target antimicrobial treatment. In recent years, new evidence with “old” biomarkers, like C-reactive protein and procalcitonin, as well as new biomarkers and molecular tests, as breathomics or bacterial DNA identification by polymerase chain reaction, increased markedly in different areas adding useful information for clinical decision making at the bedside when adequately used. The recent evidence shows that the information given by biomarkers can support the suspicion of infection and pathogen identification but also, and not less important, can exclude its diagnosis. Although the ideal biomarker has not yet been found, there are various promising biomarkers that represent true evolutions in the diagnosis of infection in patients with suspected sepsis.

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Recent developments in the management of invasive fungal infections in patients with oncohematological diseases

Therapeutic Advances in Hematology ◽

10.1177/2040620716656381 ◽

2016 ◽

Vol 7 (6) ◽

pp. 345-359 ◽

Cited By ~ 17

Author(s):

Markus Ruhnke ◽

Stefan Schwartz

Keyword(s):

Antifungal Therapy ◽

Clinical Decision Making ◽

Fungal Infections ◽

Diagnostic Procedures ◽

Clinical Decision ◽

Invasive Fungal Infections ◽

Clinical Diagnostics ◽

Diagnostic Tools ◽

Definite Diagnosis ◽

Molecular Tests

Patients with hematological cancer have a high risk of invasive fungal diseases (IFDs). These infections are mostly life threatening and an early diagnosis and initiation of appropriate antifungal therapy are essential for the clinical outcome. Most commonly, Aspergillus and Candida species are involved. However, other non- Aspergillus molds are increasingly be identified in cases of documented IFDs. Important risk factors are long lasting granulocytopenia with neutrophil counts below 500/μl for more than 10 days or graft- versus-host disease resulting from allogeneic stem-cell transplantation. For definite diagnosis of IFD, various diagnostic tools have to be applied, including conventional mycological culture and nonconventional microbiological tests such as antibody/antigen and molecular tests, as well as histopathology and radiology. In the last few years, various laboratory methods, like the Aspergillus GM immunoassay ( Aspergillus GM EIA), 1,3-ß-D-glucan (BG) assay or polymerase chain reaction (PCR) techniques have been developed for better diagnosis. Since no single indirect test, including radiological methods, provides the definite diagnosis of an invasive fungal infection, the combination of different diagnostic procedures, which include microbiological cultures, histological, serological and molecular methods like PCR together with the pattern of clinical presentation, may currently be the best strategy for the prompt diagnosis, initiation and monitoring of IFDs. Early start of antifungal therapy is mandatory, but clinical diagnostics often do not provide clear evidence of IFD. Integrated care pathways have been proposed for management and therapy of IFDs with either the diagnostic driven strategy using the preemptive antifungal therapy as opposed to the clinical or empirical driven strategy using the ‘traditional’ empirical antifungal therapy. Antifungal agents preferentially used for systemic therapy of invasive fungal infections are amphotericin B preparations, fluconazole, voriconazole, posaconazole, caspofungin, anidulafungin, micafungin, and most recently isavuconazole. Clinical decision making must consider licensing status, local experience and availability, pharmacological and economic aspects.

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Point-of-Care Testing-the Key in the Battle against SARS-CoV-2 Pandemic

Micromachines ◽

10.3390/mi12121464 ◽

2021 ◽

Vol 12 (12) ◽

pp. 1464

Author(s):

Florina Silvia Iliescu ◽

Ana Maria Ionescu ◽

Larisa Gogianu ◽

Monica Simion ◽

Violeta Dediu ◽

...

Keyword(s):

Clinical Decision Making ◽

Point Of Care ◽

Low Cost ◽

Diagnostic Testing ◽

Clinical Decision ◽

Rapid Screening ◽

Diagnostic Tools ◽

Point Of Care Testing ◽

Qrt Pcr ◽

User Friendly

The deleterious effects of the coronavirus disease 2019 (COVID-19) pandemic urged the development of diagnostic tools to manage the spread of disease. Currently, the “gold standard” involves the use of quantitative real-time polymerase chain reaction (qRT-PCR) for SARS-CoV-2 detection. Even though it is sensitive, specific and applicable for large batches of samples, qRT-PCR is labour-intensive, time-consuming, requires trained personnel and is not available in remote settings. This review summarizes and compares the available strategies for COVID-19: serological testing, Point-of-Care Testing, nanotechnology-based approaches and biosensors. Last but not least, we address the advantages and limitations of these methods as well as perspectives in COVID-19 diagnostics. The effort is constantly focused on understanding the quickly changing landscape of available diagnostic testing of COVID-19 at the clinical levels and introducing reliable and rapid screening point of care testing. The last approach is key to aid the clinical decision-making process for infection control, enhancing an appropriate treatment strategy and prompt isolation of asymptomatic/mild cases. As a viable alternative, Point-of-Care Testing (POCT) is typically low-cost and user-friendly, hence harbouring tremendous potential for rapid COVID-19 diagnosis.

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Effects of sleepiness on clinical decision making among paramedic students: a simulated night shift study

Emergency Medicine Journal ◽

10.1136/emermed-2019-209211 ◽

2021 ◽

pp. emermed-2019-209211

Author(s):

Danielle Bartlett ◽

Sara Hansen ◽

Travis Cruickshank ◽

Timothy Rankin ◽

Pauline Zaenker ◽

...

Keyword(s):

Decision Making ◽

Reaction Time ◽

Shift Work ◽

Clinical Decision Making ◽

Clinical Performance ◽

Night Shift ◽

Clinical Decision ◽

Night Shift Work ◽

Clinical Scenarios ◽

Perceived Workload

ObjectiveParamedics are at the forefront of emergency healthcare. Quick and careful decision making is required to effectively care for their patients; however, excessive sleepiness has the potential to impact on clinical decision making. Studies investigating the effects of night shift work on sleepiness, cognitive function and clinical performance in the prehospital setting are limited. Here, we aimed to determine the extent to which sleepiness is experienced over the course of a simulation-based 13-hour night shift and how this impacts on clinical performance and reaction time.MethodsTwenty-four second year paramedic students undertook a 13-hour night shift simulation study in August 2017. The study consisted of 10 real-to-life clinical scenarios. Sleepiness, perceived workload and motivation were self-reported, and clinical performance graded for each scenario. Reaction time, visual attention and task switching were also evaluated following each block of two scenarios.ResultsThe accuracy of participants’ clinical decision making declined significantly over the 13-hour night shift simulation. This was accompanied by an increase in sleepiness and a steady decline in motivation. Participants performed significantly better on the cognitive flexibility task across the duration of the simulated night shift and no changes were observed on the reaction time task. Perceived workload varied across the course of the night.ConclusionOverall, increased sleepiness and decreased clinical decision making were noted towards the end of the 13-hour simulated night shift. It is unclear the extent to which these results are reflective of practising paramedics who have endured several years of night shift work, however, this could have serious implications for patient outcomes and warrants further investigation.

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Direct oral anticoagulant monitoring: what laboratory tests are available to guide us?

Hematology ◽

10.1182/hematology.2019000027 ◽

2019 ◽

Vol 2019 (1) ◽

pp. 194-197 ◽

Cited By ~ 3

Author(s):

Ravi Sarode

Keyword(s):

Clinical Decision Making ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Rapid Assessment ◽

Clinical Decision ◽

The United States ◽

Thrombin Inhibitor ◽

Thrombin Time ◽

Clinical Scenarios

Abstract Direct oral anticoagulants (DOACs) are increasingly used in the treatment and prophylaxis of thromboembolism because of several advantages over vitamin K antagonists, including no need for laboratory monitoring. However, it has become increasingly important in certain clinical scenarios to know either actual DOAC concentration (quantitative) or presence of DOAC (qualitative). These clinical conditions include patients presenting with major bleeding or requiring urgent surgery who may need a reversal or hemostatic agent, extremes of body weight, failed therapy, etc. Prothrombin time and activated partial thromboplastin time are variably affected by factor Xa inhibitors (FXaIs) and direct thrombin inhibitor (DTI), respectively, depending on reagents’ sensitivity, and hence, they cannot be relied on confidently. Thrombin time is highly sensitive to very low amounts of DTI; thus, normal value rules out a clinically significant amount. Liquid chromatography mass spectrometry accurately measures DOAC levels but is clinically impractical. Dilute thrombin time and ecarin-based assays using appropriate calibrators/controls provide an accurate DTI level. Anti-Xa assay using corresponding FXaI calibrators/controls provides accurate drug levels. However, these assays are not readily available in the United States compared with some other parts of the world. Heparin assays using anti-Xa activity often have a linear relationship with calibrated FXaI assays, especially at the lower end of on-therapy levels, and they may provide rapid assessment of drug activity for clinical decision making. Currently, there is very limited knowledge of DOAC effect on viscoelastic measurements. Although there is uniformity in expression of DOAC concentrations in nanograms per milliliter, a universal FXaI DOAC assay is urgently needed.

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Local Ablative Therapies in Oligometastatic NSCLC: New Data and New Directions

Seminars in Respiratory and Critical Care Medicine ◽

10.1055/s-0039-3400290 ◽

2020 ◽

Vol 41 (03) ◽

pp. 369-376

Author(s):

Pencilla Lang ◽

Daniel R. Gomez ◽

David A. Palma

Keyword(s):

Clinical Decision Making ◽

Treatment Phase ◽

Progression Free Survival ◽

Clinical Decision ◽

Stereotactic Ablative Radiotherapy ◽

Free Survival ◽

Fractionated Radiotherapy ◽

Disease States ◽

Ablative Therapies ◽

Clinical Scenarios

AbstractThe oligometastatic and oligoprogressive disease states have been recently recognized as common clinical scenarios in the management of non-small cell lung cancer (NSCLC). As a result, there has been increasing interest in treating these patients with locally ablative therapies including surgery, conventionally fractionated radiotherapy, stereotactic ablative radiotherapy, and radiofrequency ablation. This article provides an overview of oligometastatic and oligoprogressive disease in the setting of NSCLC and reviews the evidence supporting ablative treatment. Phase II randomized controlled trials and retrospective series suggest that ablative treatment of oligometastases may substantially improve progression-free survival and overall survival, and additional large randomized studies testing this hypothesis in a definitive context are ongoing. However, several challenges remain, including quantifying the possible benefits of ablative therapies for oligoprogressive disease and developing prognostic and predictive models to assist in clinical decision making.

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Management of Cardiac Toxicity Induced by Chemotherapy

Journal of Clinical Medicine ◽

10.3390/jcm9092885 ◽

2020 ◽

Vol 9 (9) ◽

pp. 2885 ◽

Cited By ~ 1

Author(s):

Dario Trapani ◽

Paola Zagami ◽

Eleonora Nicolò ◽

Gabriella Pravettoni ◽

Giuseppe Curigliano

Keyword(s):

Clinical Decision Making ◽

Current Knowledge ◽

Early Recognition ◽

Clinical Decision ◽

Cancer Treatments ◽

Drug Induced ◽

Medical Interventions ◽

Clinical Scenarios ◽

New Biomarkers ◽

Chemotherapy Agents

Cardiotoxicity encompasses a spectrum of adverse cardiological effects experienced by cancer patients during and after receiving antineoplastic treatments. The intersection of cancer care with the management of the multiple comorbid non-communicable diseases carried by patients or related to cancer treatments motivates the need for an integrated and multidisciplinary approach to therapeutic clinical decision-making. This present review aimed to provide a perspective and an update of the current pharmacotherapy approaches for the prevention and management of cardiotoxicity from antiblastic chemotherapy; as such, it addresses myocardial, vascular, and arrhythmic disorders associated to chemotherapy, by navigating the current knowledge and clinical indications in support of the medical interventions. Clinical scenarios of pharmacological interventions take place with patients receiving anthracycline and, by extrapolation, other agents with cardiotoxic potentials and non-chemotherapy agents, including various small molecules and immunotherapy agents. Analysis of these scenarios aims to provide practical evidence-based guidance for the management of drug-induced cardiac dysfunctions. The possible role of new biomarkers for the early recognition of cardiotoxicity is mentioned across the clinical studies, with reference to the pharmacological biomarker-driven interventions delivered. To best inform survivorship care, the management and context of cardio-oncology services are discussed within the broader network of providers and settings of care.

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Multimodality Imaging in the Diagnostic Work-Up of Endocarditis and Cardiac Implantable Electronic Device (CIED) Infection

Journal of Clinical Medicine ◽

10.3390/jcm9072237 ◽

2020 ◽

Vol 9 (7) ◽

pp. 2237

Author(s):

Nicola Galea ◽

Francesco Bandera ◽

Chiara Lauri ◽

Camillo Autore ◽

Andrea Laghi ◽

...

Keyword(s):

Clinical Decision Making ◽

Electronic Device ◽

Multimodality Imaging ◽

Nuclear Imaging ◽

Clinical Decision ◽

Cardiac Device ◽

Systemic Complications ◽

Advantages And Disadvantages ◽

Clinical Scenarios ◽

Wide Range

Infective endocarditis (IE) is a serious cardiac condition, which includes a wide range of clinical presentations, with varying degrees of severity. The diagnosis is multifactorial and a proper characterization of disease requires the identification of the primary site of infection (usually the cardiac valve) and the search of secondary systemic complications. Early depiction of local complications or distant embolization has a great impact on patient management and prognosis, as it may induce to aggressive antibiotic treatment or, in more advanced cases, cardiac surgery. In this setting, the multimodality imaging has assumed a pivotal role in the clinical decision making and it requires the physician to be aware of the advantages and disadvantages of each imaging technique. Echocardiography is the first imaging test, but it has several limitations. Therefore, the integration with other imaging modalities (computed tomography, magnetic resonance imaging, nuclear imaging) becomes often necessary. Different strategies should be applied depending on whether the infection is suspected or already ascertained, whether located in native or prosthetic valves, in the left or right chambers, or if it involves an implanted cardiac device. In addition, detection of extracardiac IE-related lesions is crucial for a correct management and treatment. The aim of this review is to illustrate strengths and weaknesses of the various methods in the most common clinical scenarios.

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Precision Approaches in the Management of Colorectal Cancer: Current Evidence and Latest Advancements towards Individualizing the Treatment

Cancers ◽

10.3390/cancers12113481 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3481

Author(s):

Rebecca A. Shuford ◽

Ashley L. Cairns ◽

Omeed Moaven

Keyword(s):

Colorectal Cancer ◽

Growth Factor ◽

Metastatic Colorectal Cancer ◽

Mismatch Repair ◽

Clinical Decision Making ◽

Growth Factor Receptor ◽

Clinical Decision ◽

Current Evidence ◽

Therapeutic Modalities ◽

Clinically Significant

The genetic and molecular underpinnings of metastatic colorectal cancer have been studied for decades, and the applicability of these findings in clinical decision making continues to evolve. Advancements in translating molecular studies have provided a basis for tailoring chemotherapeutic regimens in metastatic colorectal cancer (mCRC) treatment, which have informed multiple practice guidelines. Various genetic and molecular pathways have been identified as clinically significant in the pathogenesis of metastatic colorectal cancer. These include rat sarcoma (RAS), epithelial growth factor receptor (EGFR), vascular endothelial growth factor VEGF, microsatellite instability, mismatch repair, and v-raf murine sarcoma viral oncogene homolog b1 (BRAF) with established clinical implications. RAS mutations and deficiencies in the mismatch repair pathway guide decisions regarding the administration of anti-EGFR-based therapies and immunotherapy, respectively. Furthermore, there are several emerging pathways and therapeutic modalities that have not entered mainstream use in mCRC treatment and are ripe for further investigation. The well-established data in the arena of targeted therapies provide evidence-based support for the use or avoidance of various therapeutic regimens in mCRC treatment, while the emerging pathways and platforms offer a glimpse into the future of transforming a precision approach into a personalized treatment.

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Ehlers-Danlos syndromes: state of the art on clinical practice guidelines

RMD Open ◽

10.1136/rmdopen-2018-000790 ◽

2018 ◽

Vol 4 (Suppl 1) ◽

pp. e000790 ◽

Cited By ~ 8

Author(s):

Alberto Sulli ◽

Rosaria Talarico ◽

Carlo Alberto Scirè ◽

Tadej Avcin ◽

Marco Castori ◽

...

Keyword(s):

Clinical Practice ◽

Clinical Practice Guidelines ◽

Practice Guidelines ◽

Clinical Decision Making ◽

Unmet Needs ◽

Musculoskeletal Diseases ◽

Clinical Decision ◽

Current Evidence ◽

Reference Network ◽

Publication Type

ObjectiveTo report the effort of the European Reference Network for Rare and Complex CONnective tissue and musculoskeletal diseases NETwork working group on Ehlers-Danlos syndromes (EDS) and related disorders to assess current available clinical practice guidelines (CPGs) specifically addressed to EDS, in order to identify potential clinician and patient unmet needs.MethodsSystematic literature search in PUBMED and EMBASE based on controlled terms (MeSH and Emtree) and keywords of the disease and publication type (CPGs). All the published articles were revised in order to identify existing CPGs on diagnosis, monitoring and treatment of EDS.ResultsLiterature revision detected the absence of papers reporting good quality CPGs to optimise EDS patient care. The current evidence-based literature regarding clinical guidelines for the EDS was limited in size and quality, and there is insufficient research exploring the clinical features and interventions, and clinical decision-making are currently based on theoretical and limited research evidences.ConclusionsMany clinician and patient unmet needs have been identified.

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