Background
Plasmodium vivax (P vivax) is a focus of malaria elimination. It is important because P vivax and Plasmodium falciparum infection are co‐endemic in some areas. There are asymptomatic ...carriers of P vivax, and the treatment for P vivax and Plasmodium ovale malaria differs from that used in other types of malaria. Rapid diagnostic tests (RDTs) will help distinguish P vivax from other malaria species to help treatment and elimination. There are RDTs available that detect P vivax parasitaemia through the detection of P vivax‐specific lactate dehydrogenase (LDH) antigens.
Objectives
To assess the diagnostic accuracy of RDTs for detecting P vivax malaria infection in people living in malaria‐endemic areas who present to ambulatory healthcare facilities with symptoms suggestive of malaria; and to identify which types and brands of commercial tests best detect P vivax malaria.
Search methods
We undertook a comprehensive search of the following databases up to 30 July 2019: Cochrane Infectious Diseases Group Specialized Register; Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE (PubMed); Embase (OVID); Science Citation Index Expanded (SCI‐EXPANDED) and Conference Proceedings Citation Index‐Science (CPCI‐S), both in the Web of Science.
Selection criteria
Studies comparing RDTs with a reference standard (microscopy or polymerase chain reaction (PCR)) in blood samples from patients attending ambulatory health facilities with symptoms suggestive of malaria in P vivax‐endemic areas.
Data collection and analysis
For each included study, two review authors independently extracted data using a pre‐piloted data extraction form. The methodological quality of the studies were assessed using a tailored Quality Assessment of Diagnostic Accuracy Studies‐2 (QUADAS‐2) tool. We grouped studies according to commercial brand of the RDT and performed meta‐analysis when appropriate. The results given by the index tests were based on the antibody affinity (referred to as the strength of the bond between an antibody and an antigen) and avidity (referred to as the strength of the overall bond between a multivalent antibody and multiple antigens). All analyses were stratified by the type of reference standard. The bivariate model was used to estimate the pooled sensitivity and specificity with 95% confidence intervals (CIs), this model was simplified when studies were few. We assessed the certainty of the evidence using the GRADE approach.
Main results
We included 10 studies that assessed the accuracy of six different RDT brands (CareStart Malaria Pf/Pv Combo test, Falcivax Device Rapid test, Immuno‐Rapid Malaria Pf/Pv test, SD Bioline Malaria Ag Pf/Pv test, OnSite Pf/Pv test and Test Malaria Pf/Pv rapid test) for detecting P vivax malaria. One study directly compared the accuracy of two RDT brands. Of the 10 studies, six used microscopy, one used PCR, two used both microscopy and PCR separately and one used microscopy corrected by PCR as the reference standard. Four of the studies were conducted in Ethiopia, two in India, and one each in Bangladesh, Brazil, Colombia and Sudan.
The studies often did not report how patients were selected. In the patient selection domain, we judged the risk of bias as unclear for nine studies. We judged all studies to be of unclear applicability concern. In the index test domain, we judged most studies to be at low risk of bias, but we judged nine studies to be of unclear applicability concern. There was poor reporting on lot testing, how the RDTs were stored, and background parasitaemia density (a key variable determining diagnostic accuracy of RDTs). Only half of the included studies were judged to be at low risk of bias in the reference standard domain, Studies often did not report whether the results of the reference standard could classify the target condition or whether investigators knew the results of the RDT when interpreting the results of the reference standard. All 10 studies were judged to be at low risk of bias in the flow and timing domain.
Only two brands were evaluated by more than one study. Four studies evaluated the CareStart Malaria Pf/Pv Combo test against microscopy and two studies evaluated the Falcivax Device Rapid test against microscopy. The pooled sensitivity and specificity were 99% (95% CI 94% to 100%; 251 patients, moderate‐certainty evidence) and 99% (95% CI 99% to 100%; 2147 patients, moderate‐certainty evidence) for CareStart Malaria Pf/Pv Combo test.
For a prevalence of 20%, about 206 people will have a positive CareStart Malaria Pf/Pv Combo test result and the remaining 794 people will have a negative result. Of the 206 people with positive results, eight will be incorrect (false positives), and of the 794 people with a negative result, two would be incorrect (false negative).
For the Falcivax Device Rapid test, the pooled sensitivity was 77% (95% CI: 53% to 91%, 89 patients, low‐certainty evidence) and the pooled specificity was 99% (95% CI: 98% to 100%, 621 patients, moderate‐certainty evidence), respectively. For a prevalence of 20%, about 162 people will have a positive Falcivax Device Rapid test result and the remaining 838 people will have a negative result. Of the 162 people with positive results, eight will be incorrect (false positives), and of the 838 people with a negative result, 46 would be incorrect (false negative).
Authors' conclusions
The CareStart Malaria Pf/Pv Combo test was found to be highly sensitive and specific in comparison to microscopy for detecting P vivax in ambulatory healthcare in endemic settings, with moderate‐certainty evidence. The number of studies included in this review was limited to 10 studies and we were able to estimate the accuracy of 2 out of 6 RDT brands included, the CareStart Malaria Pf/Pv Combo test and the Falcivax Device Rapid test. Thus, the differences in sensitivity and specificity between all the RDT brands could not be assessed. More high‐quality studies in endemic field settings are needed to assess and compare the accuracy of RDTs designed to detect P vivax.
Whether it's to proactively monitor health, diagnose a condition, or assess how well a particular treatment is working, we all undergo a variety of medical tests throughout our lives. While these ...tests provide valuable information for doctors and patients, they can sometimes carry significant risks, provide ambiguous or incorrect results, or raise more questions than they answer. Contrary to what some may think, medical testing isn't a simple "yes or no" science carried out by computers in a lab-it is a dynamic process that relies heavily on human detective work and interpretation. Medical Tests in Context: Innovations and Insights highlights more than 125 tests performed across a wide range of medical specialties. Each entry in this encyclopedia follows a standardized format that provides readers with information about how, when, and why the test is conducted; the preparation and risks; how results are determined and where errors might occur; and its history. A collection of case studies offers real-world examples of the successes-and shortcomings-of medical testing.
Diagnostic errors receive less attention than medical error though correct diagnosis remains fundamental to a patient seeking health care. Committee by the Institution of Medicine (IOM) of the ...National Academics of Sciences, Engineering, and Medicine identifies five purposes for measuring diagnostic errors.
•A lollipop swab is a simple option for COVID-19 diagnostics.•4 studies show the positives and negatives of lollipop swabs for COVID diagnostics.•Lollipop swabs performed well in patients with acute ...COVID-19 infection.
Common biologic samples used to diagnose COVID-19 include nasopharyngeal, nasal, or oropharyngeal swabs, and salivary samples. The performance characteristics of a sucked “lollipop” swab to detect SARS-CoV-2 virus is assessed in four small sub-studies.
In each sub-study, a flocked swab was sucked for 20 s and submitted for PCR detection of SARS-CoV-2 virus.
Across all studies, 52 of 69 (75.4%) COVID-19 positive participants had positive “lollipop” swabs. Twelve of the 17 COVID-19 positive participants with negative “lollipop” swabs had known corresponding cycle threshold values of >37 from their nasal/nasopharyngeal swabs, an indication of low viral load at time of sampling. In a paired samples sub-study, the sensitivity and specificity of the “lollipop” swabs were 100% and 98%.
“Lollipop” swabs performed satisfactorily especially in individuals with acute infection of COVID-19. “Lollipop” swabs are a simple method of sample collection for detecting SARS-CoV-2 virus and warrants additional consideration.
DNA nanotechnology holds substantial promise for future biomedical engineering and the development of novel therapies and diagnostic assays. The subnanometer‐level addressability of DNA ...nanostructures allows for their precise and tailored modification with numerous chemical and biological entities, which makes them fit to serve as accurate diagnostic tools and multifunctional carriers for targeted drug delivery. The absolute control over shape, size, and function enables the fabrication of tailored and dynamic devices, such as DNA nanorobots that can execute programmed tasks and react to various external stimuli. Even though several studies have demonstrated the successful operation of various biomedical DNA nanostructures both in vitro and in vivo, major obstacles remain on the path to real‐world applications of DNA‐based nanomedicine. Here, we summarize the current status of the field and the main implementations of biomedical DNA nanostructures. In particular, we focus on open challenges and untackled issues and discuss possible solutions.
Although DNA nanotechnology has spawned a broad variety of biomedical nanostructures over the last decade, these DNA nanostructures often suffer from limited stability and considerable immunogenicity. This Review introduces various biomedical applications of DNA nanostructures, describes the challenges imposed on the DNA nanostructures by the physiological environment, and discusses possible solutions to these challenges.
Summary
Due to the lack of diagnostics in primary health care, over 75 % of osteoporotic patients are not diagnosed. A new ultrasound method for primary health care is proposed. Results suggest ...applicability of ultrasound method for osteoporosis diagnostics at primary health care.
Introduction
We lack effective screening and diagnostics of osteoporosis at primary health care. In this study, a new ultrasound (US) method is proposed for osteoporosis diagnostics.
Methods
A total of 572 Caucasian women (age 20 to 91 years) were examined using pulse-echo US measurements in the tibia and radius. This method provides an estimate of bone mineral density (BMD), i.e. density index (DI). Areal BMD measurements at the femoral neck (BMD
neck
) and total hip (BMD
total
) were determined by using axial dual-energy X-ray absorptiometry (DXA) for women older than 50 years of age (
n
= 445, age = 68.8 ± 8.5 years). The osteoporosis thresholds for the DI were determined according to the International Society for Clinical Densitometry (ISCD). Finally, the FRAX questionnaire was completed by 425 participants.
Results
Osteoporosis was diagnosed in individuals with a T-score −2.5 or less in the total hip or femoral neck (
n
= 75). By using the ISCD approach for the DI, only 28.7 % of the subjects were found to require an additional DXA measurement. Our results suggest that combination of US measurement and FRAX in osteoporosis management pathways would decrease the number of DXA measurements to 16 % and the same treatment decisions would be reached at 85.4 % sensitivity and 78.5 % specificity levels.
Conclusions
The present results demonstrate a significant correlation between the ultrasound and DXA measurements at the proximal femur. The thresholds presented here with the application to current osteoporosis management pathways show promise for the technique to significantly decrease the amount of DXA referrals and increase diagnostic coverage; however, these results need to be confirmed in future studies.
The increased incidence and the significant health burden associated with carcinoma of the prostate have led to substantial changes in its diagnosis over the past century. Despite technological ...advancements, the management of prostate cancer has become progressively more complex and controversial for both early and late-stage disease. The limitations and potential harms associated with the use of prostate-specific antigen (PSA) as a diagnostic marker have stimulated significant investigation of numerous novel biomarkers that demonstrate varying capacities to detect prostate cancer and can decrease unnecessary biopsies. However, only a few of these markers have been approved for specific clinical settings while the others have not been adequately validated for use. This review systematically and critically assesses ongoing issues and emerging challenges in the current state of prostate cancer diagnostic tools and the need for disruptive next generation tools based on analysis of combinations of these biomarkers to enhance predictive accuracy which will benefit clinical diagnostics and patient welfare.
Bloodstream infections are associated with considerable morbidity and health care costs. Molecular rapid diagnostic tests (mRDTs) are a promising complement to conventional laboratory methods for the ...diagnosis of bloodstream infections and may reduce the time to effective therapy among patients with bloodstream infections. The concurrent implementation of antimicrobial stewardship programs (ASPs) may reinforce these benefits. The aim of this study was to evaluate the cost-effectivenesses of competing strategies for the diagnosis of bloodstream infection alone or combined with an ASP. To this effect, we constructed a decision-analytic model comparing 12 strategies for the diagnosis of bloodstream infection. The main arms compared the use of mRDT and conventional laboratory methods with or without an ASP. The baseline strategy used as the standard was the use of conventional laboratory methods without an ASP, and our decision-analytic model assessed the cost-effectivenesses of 5 principal strategies: mRDT (with and without an ASP), mRDT with an ASP, mRDT without an ASP, conventional laboratory methods with an ASP, and conventional laboratory methods without an ASP. Furthermore, based on the availability of data in the literature, we assessed the cost-effectivenesses of 7 mRDT subcategories, as follows: PCR with an ASP, matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) analysis with an ASP, peptide nucleic acid fluorescent
hybridization (PNA-FISH) with an ASP, a blood culture nanotechnology microarray system for Gram-negative bacteria (BC-GP) with an ASP, a blood culture nanotechnology microarray system for Gram-positive bacteria (BC-GN) with an ASP, PCR without an ASP, and PNA-FISH without an ASP. Our patient population consisted of adult inpatients in U.S. hospitals with suspected bloodstream infection. The time horizon of the model was the projected life expectancy of the patients. In a base-case analysis, cost-effectiveness was determined by calculating the numbers of bloodstream infection deaths averted, the numbers of quality-adjusted life years gained, and incremental cost-effectiveness ratios (ICERs). In a probabilistic analysis, uncertainty was addressed by plotting cost-effectiveness planes and acceptability curves for various willingness-to-pay thresholds. In the base-case analysis, MALDI-TOF analysis with an ASP was the most cost-effective strategy, resulting in savings of $29,205 per quality-adjusted life year and preventing 1 death per 14 patients with suspected bloodstream infection tested compared to conventional laboratory methods without an ASP (ICER, -$29,205/quality-adjusted life year). BC-GN with an ASP (ICER, -$23,587/quality-adjusted life year), PCR with an ASP (ICER, -$19,833/quality-adjusted life year), and PCR without an ASP (ICER, -$21,039/quality-adjusted life year) were other cost-effective options. In the probabilistic analysis, mRDT was dominant and cost-effective in 85.1% of simulations. Importantly, mRDT with an ASP had an 80.0% chance of being cost-effective, while mRDT without an ASP had only a 41.1% chance. In conclusion, our findings suggest that mRDTs are cost-effective for the diagnosis of patients with suspected bloodstream infection and can reduce health care expenditures. Notably, the combination of mRDT and an ASP can result in substantial health care savings.
Background
Accurate diagnosis of tuberculosis in people living with HIV is difficult. HIV‐positive individuals have higher rates of extrapulmonary tuberculosis and the diagnosis of tuberculosis is ...often limited to imaging results. Ultrasound is such an imaging test that is widely used as a diagnostic tool (including point‐of‐care) in people suspected of having abdominal tuberculosis or disseminated tuberculosis with abdominal involvement.
Objectives
To determine the diagnostic accuracy of abdominal ultrasound for detecting abdominal tuberculosis or disseminated tuberculosis with abdominal involvement in HIV‐positive individuals.
To investigate potential sources of heterogeneity in test accuracy, including clinical setting, ultrasound training level, and type of reference standard.
Search methods
We searched for publications in any language up to 4 April 2019 in the following databases: MEDLINE, Embase, BIOSIS, Science Citation Index Expanded (SCI‐EXPANDED), Social Sciences Citation Index (SSCI), Conference Proceedings Citation Index‐ Science (CPCI‐S), and also ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform to identify ongoing trials.
Selection criteria
We included cross‐sectional, cohort, and diagnostic case‐control studies (prospective and retrospective) that compared the result of the index test (abdominal ultrasound) with one of the reference standards. We only included studies that allowed for extraction of numbers of true positives (TPs), true negatives (TNs), false positives (FPs), and false negatives (FNs). Participants were HIV‐positive individuals aged 15 years and older. A higher‐quality reference standard was the bacteriological confirmation of Mycobacterium tuberculosis from any clinical specimen, and a lower‐quality reference standard was a clinical diagnosis of tuberculosis without microbiological confirmation. We excluded genitourinary tuberculosis.
Data collection and analysis
For each study, two review authors independently extracted data using a standardized form. We assessed the quality of studies using a tailored Quality Assessment of Diagnostic Accuracy Studies‐2 (QUADAS‐2) tool. We used the bivariate model to estimate pooled sensitivity and specificity. When studies were few we simplified the bivariate model to separate univariate random‐effects logistic regression models for sensitivity and specificity. We explored the influence of the type of reference standard on the accuracy estimates by conducting separate analyses for each type of reference standard. We assessed the certainty of the evidence using the GRADE approach.
Main results
We included 11 studies. The risks of bias and concern about applicability were often high or unclear in all domains. We included six studies in the main analyses of any abnormal finding on abdominal ultrasound; five studies reported only individual lesions.
The six studies of any abnormal finding were cross‐sectional or cohort studies. Five of these (83%) were conducted in low‐ or middle‐income countries, and one in a high‐income country. The proportion of participants on antiretroviral therapy was none (1 study), fewer then 50% (4 studies), more than 50% (1 study), and not reported (5 studies). The first main analysis, studies using a higher‐quality reference standard (bacteriological confirmation), had a pooled sensitivity of 63% (95% confidence interval (CI) 43% to 79%; 5 studies, 368 participants; very low‐certainty evidence) and a pooled specificity of 68% (95% CI 42% to 87%; 5 studies, 511 participants; very low‐certainty evidence). If the results were to be applied to a hypothetical cohort of 1000 people with HIV where 200 (20%) have tuberculosis then:
‐ About 382 individuals would have an ultrasound result indicating tuberculosis; of these, 256 (67%) would be incorrectly classified as having tuberculosis (false positives).
‐ Of the 618 individuals with a result indicating that tuberculosis is not present, 74 (12%) would be incorrectly classified as not having tuberculosis (false negatives).
In the second main analysis involving studies using a lower‐quality reference standard (clinical diagnosis), the pooled sensitivity was 68% (95% CI 45% to 85%; 4 studies, 195 participants; very low‐certainty evidence) and the pooled specificity was 73% (95% CI 41% to 91%; 4 studies, 202 participants; very low‐certainty evidence).
Authors' conclusions
In HIV‐positive individuals thought to have abdominal tuberculosis or disseminated tuberculosis with abdominal involvement, abdominal ultrasound appears to have 63% sensitivity and 68% specificity when tuberculosis was bacteriologically confirmed. These estimates are based on data that is limited, varied, and low‐certainty.
The low sensitivity of abdominal ultrasound means clinicians should not use a negative test result to rule out the disease, but rather consider the result in combination with other diagnostic strategies (including clinical signs, chest x‐ray, lateral flow urine lipoarabinomannan assay (LF‐LAM), and Xpert MTB/RIF). Research incorporating the test into tuberculosis diagnostic algorithms will help in delineating more precisely its value in diagnosing abdominal tuberculosis or disseminated tuberculosis with abdominal involvement.
26 September 2019
Up to date
All studies incorporated from most recent search
All studies identified during the most recent search (4 Apr, 2019) have been incorporated in the review, and one ongoing study identified
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