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Journal of Clinical Microbiology Sep 2019The timely and accurate diagnosis of respiratory virus infections has the potential to optimize downstream (posttesting) use of limited health care resources, including... (Comparative Study)
Comparative Study Review
The timely and accurate diagnosis of respiratory virus infections has the potential to optimize downstream (posttesting) use of limited health care resources, including antibiotics, antivirals, ancillary testing, and inpatient and emergency department beds. Cost-effective algorithms for respiratory virus testing must take into consideration numerous factors, including which patients should be tested, what testing should be performed (for example, antigen testing versus reverse transcription-PCR testing or influenza A/B testing versus testing with a comprehensive respiratory virus panel), and the turnaround time necessary to achieve the desired posttesting outcomes. Despite the clinical impact of respiratory virus infections, the cost-effectiveness of respiratory virus testing is incompletely understood. In this article, we review the literature pertaining to the cost-effectiveness of respiratory virus testing in pediatric and adult patient populations, in emergency department, outpatient, and inpatient clinical settings. Furthermore, we consider the cost-effectiveness of a variety of testing methods, including rapid antigen tests, direct fluorescent antibody assays, and nucleic acid amplification tests.
Topics: Cost-Benefit Analysis; Diagnostic Tests, Routine; Humans; Immunoassay; Molecular Diagnostic Techniques; Respiratory Tract Infections; Virus Diseases
PubMed: 31142607
DOI: 10.1128/JCM.00373-19 -
American Journal of Clinical Pathology Jul 2019To provide a clinical laboratory perspective on the Verifying Accurate Leading-edge IVCT Development Act (VALID) discussion draft. This potential legislative effort, if... (Review)
Review
OBJECTIVES
To provide a clinical laboratory perspective on the Verifying Accurate Leading-edge IVCT Development Act (VALID) discussion draft. This potential legislative effort, if enacted, would overhaul the regulatory oversight of in vitro diagnostics (IVDs) in the United States and create a single system for regulation of conventional IVDs and laboratory-developed tests (LDTs).
METHODS
A concise literature-based review of LDT regulation is presented followed by a discussion of key concerns pertinent to clinical laboratories that should be considered in future IVD regulatory reform efforts.
RESULTS
Key issues identified include the importance of fostering innovation, preserving patient safety, protecting the practice of laboratory medicine, and minimizing undue regulatory burden. Clinical laboratories are not equivalent to manufacturing facilities and would therefore encounter challenges in implementing device-centric regulatory oversight models.
CONCLUSIONS
It is imperative that a clinical laboratory perspective on LDTs is understood and incorporated prior to advancement of future legislative proposals.
Topics: Clinical Laboratory Services; Diagnostic Tests, Routine; Humans; United States; United States Food and Drug Administration
PubMed: 31242284
DOI: 10.1093/ajcp/aqz096 -
ACS Sensors Oct 2020Biological signaling pathways are underpinned by protein switches that sense and respond to molecular inputs. Inspired by nature, engineered protein switches have been... (Review)
Review
Biological signaling pathways are underpinned by protein switches that sense and respond to molecular inputs. Inspired by nature, engineered protein switches have been designed to directly transduce analyte binding into a quantitative signal in a simple, wash-free, homogeneous assay format. As such, they offer great potential to underpin point-of-need diagnostics that are needed across broad sectors to improve access, costs, and speed compared to laboratory assays. Despite this, protein switch assays are not yet in routine diagnostic use, and a number of barriers to uptake must be overcome to realize this potential. Here, we review the opportunities and challenges in engineering protein switches for rapid diagnostic tests. We evaluate how their design, comprising a recognition element, reporter, and switching mechanism, relates to performance and identify areas for improvement to guide further optimization. Recent modular switches that enable new analytes to be targeted without redesign are crucial to ensure robust and efficient development processes. The importance of translational steps toward practical implementation, including integration into a user-friendly device and thorough assay validation, is also discussed.
Topics: Biosensing Techniques; Diagnostic Tests, Routine; Protein Engineering; Proteins
PubMed: 33052043
DOI: 10.1021/acssensors.0c01831 -
Journal of Clinical Microbiology Sep 2019Advanced microbiology technologies are rapidly changing our ability to diagnose infections, improve patient care, and enhance clinical workflow. These tools are... (Review)
Review
Advanced microbiology technologies are rapidly changing our ability to diagnose infections, improve patient care, and enhance clinical workflow. These tools are increasing the breadth, depth, and speed of diagnostic data generated per patient, and testing is being moved closer to the patient through rapid diagnostic technologies, including point-of-care (POC) technologies. While select stakeholders have an appreciation of the value/importance of improvements in the microbial diagnostic field, there remains a disconnect between clinicians and some payers and hospital administrators in terms of understanding the potential clinical utility of these novel technologies. Therefore, a key challenge for the clinical microbiology community is to clearly articulate the value proposition of these technologies to encourage payers to cover and hospitals to adopt advanced microbiology tests. Specific guidance on how to define and demonstrate clinical utility would be valuable. Addressing this challenge will require alignment on this topic, not just by microbiologists but also by primary care and emergency room (ER) physicians, infectious disease specialists, pharmacists, hospital administrators, and government entities with an interest in public health. In this article, we discuss how to best conduct clinical studies to demonstrate and communicate clinical utility to payers and to set reasonable expectations for what diagnostic manufacturers should be required to demonstrate to support reimbursement from commercial payers and utilization by hospital systems.
Topics: Communicable Diseases; Diagnostic Tests, Routine; Humans; Microbiological Techniques; Point-of-Care Systems
PubMed: 31217268
DOI: 10.1128/JCM.00495-19 -
Nature Genetics Aug 2019
Topics: Chromosomes; Diagnostic Tests, Routine; Gene Expression
PubMed: 31332379
DOI: 10.1038/s41588-019-0476-x -
Revue Scientifique Et Technique... Jun 2021Latent class analysis (LCA) has allowed epidemiologists to overcome the practical constraints faced by traditional diagnostic test evaluation methods, which require both... (Review)
Review
Latent class analysis (LCA) has allowed epidemiologists to overcome the practical constraints faced by traditional diagnostic test evaluation methods, which require both a gold standard diagnostic test and ample numbers of appropriate reference samples. Over the past four decades, LCA methods have expanded to allow epidemiologists to evaluate diagnostic tests and estimate true prevalence using imperfect tests over a variety of complex data structures and scenarios, including during the emergence of novel infectious diseases. The objective of this review is to provide an overview of recent developments in LCA methods, as well as a practical guide to applying Bayesian LCA (BLCA) to the evaluation of diagnostic tests. Before conducting a BLCA, the suitability of BLCA for the pathogen of interest, the availability of appropriate samples, the number of diagnostic tests, and the structure of the data should be carefully considered. While formulating the model, the model's structure and specification of informative priors will affect the likelihood that useful inferences can be drawn. With the growing need for advanced analytical methods to evaluate diagnostic tests for newly emerging diseases, LCA is a promising field of research for both the veterinary and medical disciplines.
Topics: Animals; Bayes Theorem; Communicable Diseases; Diagnostic Tests, Routine; Latent Class Analysis; Reference Standards; Sensitivity and Specificity
PubMed: 34140724
DOI: 10.20506/rst.40.1.3224 -
Epilepsy & Behavior : E&B Dec 2019Convulsive status epilepticus (SE) is a relatively common emergency condition affecting individuals of all ages. The primary goal of treatment is prompt termination of... (Review)
Review
Convulsive status epilepticus (SE) is a relatively common emergency condition affecting individuals of all ages. The primary goal of treatment is prompt termination of seizures. Where first-line treatment with benzodiazepine has failed to achieve this, a condition known as established SE (ESE), there is uncertainty about which agent to use next. The Established Status Epilepticus Treatment Trial (ESETT) is a 3-arm (valproate (VPA), fosphenytoin (FOS), levetiracetam (LEV)), phase III, double-blind randomized comparative effectiveness study in patients aged 2 years and above with established convulsive SE. Enrollment was completed in January 2019, and the results are expected later this year. We discuss lessons learnt during the conduct of the study in relation to the following: ethical considerations; trial design and practical implementation in emergency settings, including pediatric and adult populations; quality assurance; and outcome determination where treating emergency clinicians may lack specialist expertise. We consider that the ESETT is already informing both clinical practice and future trial design. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures".
Topics: Adult; Anticonvulsants; Benzodiazepines; Child, Preschool; Clinical Trials as Topic; Diagnostic Tests, Routine; Double-Blind Method; Emergency Service, Hospital; Female; Humans; Levetiracetam; Male; Status Epilepticus; Treatment Outcome; Valproic Acid
PubMed: 31653603
DOI: 10.1016/j.yebeh.2019.04.049 -
Viruses Apr 2021Prion diseases are difficult to recognize as many symptoms are shared among other neurologic pathologies and the full spectra of symptoms usually do not appear until... (Review)
Review
Prion diseases are difficult to recognize as many symptoms are shared among other neurologic pathologies and the full spectra of symptoms usually do not appear until late in the disease course. Additionally, many commonly used laboratory markers are non-specific to prion disease. The recent introduction of second-generation real time quaking induced conversion (RT-QuIC) has revolutionized pre-mortem diagnosis of prion disease due to its extremely high sensitivity and specificity. However, RT-QuIC does not provide prognostic data and has decreased diagnostic accuracy in some rarer, atypical prion diseases. The objective of this review is to provide an overview of the current clinical utility of fluid-based biomarkers, neurodiagnostic testing, and brain imaging in the diagnosis of prion disease and to suggest guidelines for their clinical use, with a focus on rarer prion diseases with atypical features. Recent advancements in laboratory-based testing and imaging criteria have shown improved diagnostic accuracy and prognostic potential in prion disease, but because these diagnostic tests are not sensitive in some prion disease subtypes and diagnostic test sensitivities are unknown in the event that CWD transmits to humans, it is important to continue investigations into the clinical utility of various testing modalities.
Topics: Animals; Biomarkers; Creutzfeldt-Jakob Syndrome; Diagnosis, Differential; Diagnostic Tests, Routine; Disease Susceptibility; Electroencephalography; Genetic Predisposition to Disease; Humans; Magnetic Resonance Imaging; Neurodegenerative Diseases; Prion Diseases; Prions; Quality Improvement; Sensitivity and Specificity; Zoonoses
PubMed: 33925126
DOI: 10.3390/v13050789 -
F1000Research 2019Recent research in the field of osteoarthritis (OA) has focused on understanding the underlying molecular and clinical phenotypes of the disease. This narrative review... (Review)
Review
Recent research in the field of osteoarthritis (OA) has focused on understanding the underlying molecular and clinical phenotypes of the disease. This narrative review article focuses on recent advances in our understanding of the phenotypes of OA and proposes that the disease represents a diversity of clinical phenotypes that are underpinned by a number of molecular mechanisms, which may be shared by several phenotypes and targeted more specifically for therapeutic purposes. The clinical phenotypes of OA supposedly have different underlying etiologies and pathogenic pathways and they progress at different rates. Large OA population cohorts consist of a majority of patients whose disease progresses slowly and a minority of individuals whose disease may progress faster. The ability to identify the people with relatively rapidly progressing OA can transform clinical trials and enhance their efficiency. The identification, characterization, and classification of molecular phenotypes of rapidly progressing OA, which represent patients who may benefit most from intervention, could potentially serve as the basis for precision medicine for this disabling condition. Imaging and biochemical markers (biomarkers) are important diagnostic and research tools that can assist with this challenge.
Topics: Biomarkers; Diagnostic Tests, Routine; Humans; Osteoarthritis; Phenotype; Precision Medicine
PubMed: 31885861
DOI: 10.12688/f1000research.20575.1 -
Annual Review of Analytical Chemistry... Jul 2021Early disease diagnosis is necessary to enable timely interventions. Implementation of this vital task in the developing world is challenging owing to limited resources.... (Review)
Review
Early disease diagnosis is necessary to enable timely interventions. Implementation of this vital task in the developing world is challenging owing to limited resources. Diagnostic approaches developed for resource-limited settings have often involved colorimetric tests (based on immunoassays) due to their low cost. Unfortunately, the performance/sensitivity of such simplistic tests are often limited and significantly hinder opportunities for early disease detection. A new criterion for selecting diagnostic tests in low- and middle-income countries is proposed here that is based on performance-to-cost ratio. For example, modern mass spectrometry (MS) now involves analysis of the native sample in the open laboratory environment, enabling applications in many fields, including clinical research, forensic science, environmental analysis, and agriculture. In this critical review, we summarize recent developments in chemistry that enable MS to be applied effectively in developing countries. In particular, we argue that closed automated analytical systems may not offer the analytical flexibility needed in resource-limited settings. Alternative strategies proposed here have potential to be widely accepted in low- and middle-income countries through the utilization of the open-source ambient MS platform that enables microsampling techniques such as dried blood spot to be coupled with miniature mass spectrometers in a centralized analytical platform. Consequently, costs associated with sample handling and maintenance can be reduced by >50% of the total ownership cost, permitting analytical measurements to be operated at high performance-to-cost ratios in the developing world.
Topics: Chemistry, Clinical; Developing Countries; Diagnostic Tests, Routine; Mass Spectrometry
PubMed: 33979544
DOI: 10.1146/annurev-anchem-091520-085936