File Name: diagnostic and laboratory tests .zip
This book offers a comprehensive collection of high-definition photos and illustrations depicting the step-by-step process of carrying out various lab tests. The related tests have been organized together so that you can navigate and learn each type of diagnostic test easily. We hope that people belonging to this area of practice will find this book useful in their studies.
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Hundreds of molecular tests and immunoassays were rapidly developed, albeit many still await clinical validation and formal approval. We explore the technical and implementation problems encountered during this early phase in the pandemic, and try to define future directions for the progressive and better use of syndromic diagnostics during a possible resurgence of COVID in future global waves or regional outbreaks.
Continuous global improvement in diagnostic test preparedness is essential for more rapid detection of patients, possibly at the point of care, and for optimized prevention and treatment, in both industrialized countries and low-resource settings. During a pandemic there are multiple concurrent clinical priorities, including the need to understand the pathophysiology of the disease, optimized patient care and prevention of future infections 1.
The detection and characterization of the etiological agent or its immunological consequences in the host are the necessary starting points 2. Being able to define the pathogen, biologically and genetically, and whether it is inducing protective immunity are key in the development of protective and curative protocols against future persisting disease. The current diagnostic procedures are twofold. First there is the direct detection of parts of the virus.
This can be done by culture of the virus, detection of one or more of its proteins and, the method used most frequently during the present pandemic, direct detection of nucleic acids or detection via amplification of nucleic acids. Immunological tests detect the consequences of infection by the virus in the host.
This is most frequently focused on the detection of virus-specific antibodies, whereas some specialized laboratories may also be capable of defining the cellular immune response. Here we will mostly focus on the nucleic amplification tests, with illustrations of how immune tests may complement molecular tests in several cases. Diagnostics can be used in various manners, the so-called use cases.
These include triage of symptomatic individuals in an epidemic or endemic setting, triage of at-risk presymptomatic and symptomatic individuals in endemic settings, confirmatory testing, diagnosis of symptomatic individuals in endemic or epidemic settings, differential diagnosis in endemic or epidemic settings, testing of patients with previous exposure to severe acute respiratory syndrome coronavirus 2 SARS-CoV-2; the cause of the coronavirus disease COVID pandemic , surveillance at sites of previous or potential outbreaks and environmental monitoring Foundation for Innovative New Diagnostics FIND.
The use case determines the way in which diagnostic tests are used optimally 3. The ongoing COVID pandemic has underpinned the central position of diagnostic testing in outbreak control 4. Ending the pandemic involves the accurate application of diagnostic testing in high volumes and the rapid use of the results to help implement the appropriate therapy and prevent further spread. The value of integrated diagnostics in the management of the current COVID wave and possible future COVID waves is high, especially for the molecular detection of the virus, and for the qualification and quantification of the immunological host response 5.
Test design, validation and verification, emergency use approval and the manufacturing of test kits in very high numbers are just a few examples of such obstacles. From the perspective of a routine-diagnostic microbiology laboratory, the setting up of high-throughput diagnostic pipelines, the logistics involved and the optimization of pragmatic use of test results were encountered as important problems during the first wave of the ongoing COVID pandemic.
Ultimately, optimized diagnostic tools will provide guidance in the development of therapeutics and vaccines Fig. Diagnostic lessons learnt during the first wave of the COVID pandemic should be used to help prepare for the next wave, which is anticipated by many. The boxes on the left identify some of the important medical, scientific and industrial deliverables where an interconnected approach covering each steps from fundamental research to commercialization is needed.
Translational medicine relies on the interconnection of multidisciplinary teams of life scientists able to translate basic scientific discoveries into changes in clinical practice supported by expertise from engineering, law and financial sciences. The most important facilitators are indicated in each box.
The column on the right lists the innovation drivers. Current innovation drivers combine the ability to process large amounts of data and to facilitate access to biological material through easy access to a biobank. The intense collaboration between academia and industry, with detailed sharing of research goals and directions during the coronavirus disease COVID pandemic, through the identification of an optimal collaborative approach capitalizing on the strengths of both made possible the rapid development of new diagnostic tests, drugs and possible vaccines against COVID In this Review we address early COVID test design and the design-, development-, production- and distribution-associated hurdles.
We discuss the importance of quality control and options for mass production as well as the practical issues around broad and rapid implementation of entirely new tests that have not undergone classic evaluation and validation.
We also estimate the effect of new-generation COVID tests on laboratory medicine practice, the need for new approaches towards biobanking and the economic consequences of the pandemic. Of note, we focus on molecular assays, with limited presentation and explanation of serological tests.
For adaption towards the more frequently used diagnostic DNA detection formats, the viral genome needs to be transcribed into a DNA complement by reverse transcriptase. Moreover, monitoring the host response is important in identifying individuals who have already been infected with SARS-CoV-2 as well as for assessing future vaccine efficacy.
Over the past months, all currently available technologies have been exploited to rapidly develop highly sensitive and highly specific detection and characterization assays for SARS-CoV In this section we briefly discuss these test formats, but we will not consider functional tests that assess virus inactivation or the therapeutic effect of cellular immune responses 1. Such assays are mostly limited to highly specialized laboratories and do not yet have a major impact on current global health-care practice.
Moreover, rapid antigen detection tests have also been developed to detect active infection, although a limited number of such tests are available 14 , However, in comparison with rtPCR, rapid antigen detection tests lack sensitivity, and owing to the increased risk of false-negative results, they are considered as an adjunct to rtPCR tests 16 , Antibody testing can have a mostly complementary role to rtPCR tests in the diagnosis of COVID, at approximately 10 days or more after the onset of symptoms, in assessing past infections and defining the dynamics of the individual humoral responses in individual patients or in patient cohorts undergoing certain forms of treatment 20 , Targets for the tests have been identified by comparative screening for genomic regions that have a low mutation frequency to avoid primer and antibody mismatches, and enhance test quality and stability Hundreds of such diagnostic tests have now been developed Supplementary Table 1 , and technical reviews of their comparative performance assessment have been published recently 25 , 26 , 27 , 28 , 29 , 30 , 31 , It is important to note that all novel tests urgently need useful clinical cut-off values to help enhance their medical value At present, negative results in either of these test types do not completely rule out current or past infections owing to possible false-negative results 36 , Quantitative test results may be a prerequisite for the choice of COVID treatment strategy, for treatment follow-up or for the support of vaccine trials.
Another important aspect is surveillance: the rapid and continuous detection efforts aimed at early recognition, isolation and treatment of those infected with the virus For adequate surveillance and tracing, both regionally and globally epidemiological virus typing is important.
Next-generation nucleotide sequencing is used to define polymorphisms and to define interrelatedness between virus strains 39 , Such approaches have been instrumental in defining the global spread of the virus and may also help to define virus variants with different biological capacities for example, ease of spread, pathogenicity and tissue tropism.
Metagenomic next-generation nucleotide sequencing can also be used diagnostically for virus detection in patients 41 or in environmental samples such as wastewater The superficial sketch of test design provided in the previous subsection represents only the first steps in test development. Initial design, experimental small-scale laboratory validation and, if at all possible, clinical evaluation using high-quality and patient specimens are followed by industrial scale-up.
The test format needs to be compatible with large-scale production, which in the case of COVID was possible for tests that were supported on pre-existing platforms Any test that was developed rapidly but was not applicable on an existing instrument had a substantial disadvantage to reach the market Possible exceptions are tests that are presented in a platform-agnostic layout and that can be combined with any type of instrument already available to laboratory-based diagnosticians Moreover, instruments and tests need to be abundantly available at a local and global scale to ensure scale-up of clinical testing.
The preavailability of a platform also enables the broad geographical spread of the test. If an installed base of instruments already exists, then new tests in the already existing format can be rapidly and reliably added to the testing repertoire of a laboratory. In such cases, assay transport and storage are two remaining hurdles, and test distribution in itself may be an important obstacle.
The shelf life of a test, the temperature tolerance of the test components and simple characteristics such as the size and weight of the package are all important parameters in the perceived ease of distribution. Once the instrument and assays are available to users, instrument availability and human expertise may still be limiting factors in high-throughput test application It is clear that the entire global population cannot be tested repeatedly at the same time, and choices need to be made to prioritize patient groups or groups at increased risk of being infected for example, health-care workers When these groups have been identified, sampling processes and their logistics need to be designed and implemented.
Simplicity of sampling and homogeneity of the sample itself are important parameters to consider, and other sources, such as saliva, have been considered as alternative specimens for COVID testing Testing of sample pools has been suggested as a solution to minimize test costs while maintaining test sensitivity and specificity, specifically in settings where the incidence of infection is low The jury is still out on whether pooling is diagnostically robust and cost-effective, with conflicting reports having been published 50 , 51 , In addition, the current consensus is that individual laboratories should perform validation studies before embarking on large-scale pooling strategies Finally, there is a continuous need for means of rapid and reliable result dissemination, an issue that is covered in privacy loopholes but also the need to use test results beyond the privacy of an individual patient.
Test results are key in surveillance and outbreak management and should be used to inform infection prevention measures. Diagnostic tests need careful consideration and validation before being launched. This is often underestimated and underappreciated by scientists and the community, and involves processes that are costly and time-consuming. The EUA by the US Food and Drug Administration FDA covers for most of the more common test quality parameters for example, sensitivity, specificity, positive and negative predictive values, robustness and reproducibility.
In addition, the provision of positive control templates was effectively implemented by the European Virus Archive goes Global EVAg project, supplying specific products such as RNA transcripts for assays through its online catalogue by mid-January refs 54 , Technical qualification data, based on the use of cell culture materials and synthetic nucleic acid constructs, as well as results from exclusivity testing of 75 clinical samples, were included in the first diagnostic protocol provided to the WHO on 13 January Unfortunately, and despite this EUA registration, as described in a news article , there were problems with one of the reagents described in the CDC protocol, partially blocking rapid implementation of the test or leading to retraction of test results.
On 29 February , new guidance was issued for laboratories to be able to develop and implement COVID molecular diagnostic tests before obtaining EUA 58 , 59 , 60 , 61 see also Supplementary Table 1. Diagnostic testing without quality control at all levels from design up and until end use is without value and results in abuse of valuable and possibly scarce resources.
The analytical specificity of a molecular COVID test is its ability to determine exclusively the analyte it intends to measure in the presence of off-target templates or interfering substances under well-controlled laboratory conditions. The analytical sensitivity of an assay often describes the lowest amount of analyte that can be accurately measured through an assay.
Adequate analytical specificity and sensitivity will in the end lead to optimal clinical performance. For molecular COVID tests, the quality and relevant abundance of RNA in collected samples which is heavily dependent on the type and site of collection are crucial for the sensitivity of the assays 62 , In this study, blood samples were obtained from 23 patients, and rectal swabs were obtained from 15 patients.
The analytical sensitivity of the new molecular tests was reported to be high from the outset, even though a number of studies had to use target material from cultures of Vero cells or synthetic viral DNA fragments owing to the regulatory inability to access samples from the early infected populations in China This validation was repeated with clinically available samples from infected patients in Europe and other geographical regions, including North America and South America.
This implies that for none of the currently used COVID tests is the absolute sensitivity RNA genomes per millilitre known because there simply is not a clear gold standard for testing available for a pathogen that has been known for about half a year.
It is relevant to note that it is difficult to obtain precise test quality data on locally used tests in China. In general, the limitations of many of the published validation studies for COVID diagnostic tests were low sample numbers, the differences in the processes for collection, storage and processing of samples before the diagnostic tests preanalytical bias and the lack of validation by independent third parties.
All of the studies were performed using disperse clinical parameters, a feature also hampering the development of diagnostic tests during previous coronavirus outbreaks These are not necessarily new aspects 67 , although the need for timely delivery of new diagnostic assays allowed them to re-emerge.
An entirely novel aspect during this outbreak was the widespread use of preprint servers for sharing research data before peer-review for example, medRxiv or bioRxiv , where studies appeared evaluating the relative performances of different diagnostic technologies Still, caution should be exercised with interpretation of non-peer-reviewed manuscripts, and whether easier access to technical and comparative information has been instrumental in getting the tests to the market sooner or increasing their end-user adoption remains to be addressed Affordability, sensitivity, specificity, user-friendliness, rapidity and robustness, being free of equipment and being easily deliverable to end users are the key drivers towards diagnostic readiness under difficult circumstances.
In addition, the clinical validation in low-resource settings needs to establish diagnostic performance in the target population with its co-endemic diseases, some of which may be seasonal or geographically disperse Most of the laboratories located in low-resource settings may not possess the costly platforms needed to run well-performing commercial tests.
Skip to search form Skip to main content You are currently offline. Some features of the site may not work correctly. Dunning Published Medicine. Prepare your students to deliver safe, effective, and informed care for patients who are undergoing diagnostic tests and procedures with the Ninth Edition of A Manual of Laboratory and Diagnostic Tests. Organized the way a nurse thinks by specimen and function this proven book describes an extensive array of tests for diverse populations, providing step-by-step guidance on correct procedure, tips for accurate interpretation, and expert information on patient preparation and aftercare. Save to Library. Create Alert.
Skip to search form Skip to main content You are currently offline. Some features of the site may not work correctly. Covering 25 categories of tests, this guide presents information to enhance patient care planning and implementation. For each type of test, information is provided on anatomic, physiological, and pathophysiological understandings of procedures; reference values, including variations related to age. Save to Library. Create Alert. Launch Research Feed.
Consultants with clinicians, other healthcare providers, and patients regarding laboratory test selection and test results interpretation. For example, the acutely ill jaundiced patient with a history of prolonged alcohol ingestion requires a different laboratory assessment than the well patient in whom one or more standard liver test results are discovered to be abnormal during routine testing. A Federal law, the Clinical Laboratory Improvement Act, regulates all aspects of clinical laboratory testing. Many factors affect test results. GaTate, a somatostatin analog, has recently. Clinical Laboratory Improvement Amendments. Definitive diagnosis is now made earlier as well as more correctly than in the past.
This is a list of medical tests and procedures used to obtain health information and diagnose pathological and nonpathological conditions of the human body. It is grouped by type of procedure and ordered alphabetically. See also d diagnosis ; medicine ; pathology.
This book offers a comprehensive collection of high-definition photos and illustrations depicting the step-by-step process of carrying out various lab tests. The related tests have been organized together so that you can navigate and learn each type of diagnostic test easily. We hope that people belonging to this area of practice will find this book useful in their studies. We have uploaded this PDF ebook to our online file repository so that you access it without any trouble.
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Many diagnostic and laboratory tests include the direction to perform routine blood testing and/or routine urine testing. The protocol for those tests is presented.Reply
In recent years, a wide range of diagnostic tests has become available for use in resource-constrained settings.Reply