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Expert Review of Molecular Diagnostics Jan 2020: The development of point-of-care testing (POCT) has made clinical diagnostics available, affordable, rapid, and easy to use since the 1990s.The significance of this... (Review)
Review
: The development of point-of-care testing (POCT) has made clinical diagnostics available, affordable, rapid, and easy to use since the 1990s.The significance of this platform rests on its potential to empower patients to monitor their own health status more frequently, in the convenience of their home, so that diseases can be diagnosed at the earliest possible time-point. Recent advances have expanded traditional formats such as qualitative or semi-quantitative dipsticks and lateral flow immunoassays to newer platforms such as microfluidics and paper-based assays where signals can be measured quantitatively using handheld devices.: This review discusses: (1) working principles and operating mechanisms of both existing and emerging POCT platforms, (2) urine analytes measured using POCT in comparison to the laboratory or clinical 'gold standard,' and (3) limitations of existing POCT and expectations of emerging POCT in urinalysis.: Currently, a variety of biological samples such as urine, saliva, serum, plasma, and other fluids can be applied to POCT for quick diagnosis, especially in resource-limited settings. Emerging platforms will increasingly empower individuals to monitor their health status through frequent urine analysis even from their homes. The impact of these emerging technologies on healthcare is likely to be transformative.
Topics: Humans; Immunoassay; Microfluidics; Molecular Diagnostic Techniques; Point-of-Care Systems; Urinalysis
PubMed: 31795785
DOI: 10.1080/14737159.2020.1699063 -
European Journal of Internal Medicine Jan 2021Urinalysis and urine culture are two of the most commonly ordered tests. A positive urine test in asymptomatic patients often leads to overtreatment. Antimicrobials for...
BACKGROUND
Urinalysis and urine culture are two of the most commonly ordered tests. A positive urine test in asymptomatic patients often leads to overtreatment. Antimicrobials for asymptomatic bacteriuria is one of the most common unnecessary treatments. We aimed to explore the current ordering patterns of urinalysis and cultures.
METHODS
This is a substudy of the multicentre RICAT-trial, a successful quality improvement project to reduce inappropriate use of intravenous and urinary catheters in seven hospitals in the Netherlands. Adult patients with a (central or peripheral) venous or urinary catheter admitted to internal medicine and non-surgical subspecialty wards were eligible for inclusion. Data were collected every other week during baseline (seven months) and intervention periods (seven months). The primary outcome was the proportion of urine cultures performed following a negative urinalysis, i.e. dipstick and/or microscopic analysis, within 24 h.
RESULTS
Between September 2016 and April 2018, we included 3748 patients, of which 3111 (83%) were admitted from the emergency department. Urinalysis and/or urine cultures were obtained in 2610 (70%) of 3748 patients. 626 (23.7%) of 2636 urine cultures and 1351 (55.8%) of 2419 microscopic analysis were unnecessary performed after a negative urinalysis. Cancelling urine testing orders after a negative dipstick would have saved almost € 19.500 during the study period in these seven hospitals.
CONCLUSION
Unnecessary urine testing is frequent in non-surgical patients in the Netherlands. We need to take action to reduce unnecessary urinalysis and cultures, and thereby probably reduce overtreatment of asymptomatic bacteriuria.
Topics: Adult; Bacteriuria; Humans; Netherlands; Urinalysis; Urinary Catheters; Urinary Tract Infections; Urine
PubMed: 32830036
DOI: 10.1016/j.ejim.2020.08.013 -
Parasite (Paris, France) 2021Toxoplasma gondii is an obligate intracellular protozoan parasite that causes toxoplasmosis and threatens warm-blooded animal and human health worldwide. Simple and...
Toxoplasma gondii is an obligate intracellular protozoan parasite that causes toxoplasmosis and threatens warm-blooded animal and human health worldwide. Simple and applicable diagnostic methods are urgently needed to guide development of effective approaches for prevention of toxoplasmosis. Most molecular diagnostic tools for T. gondii infection require high technical skills, sophisticated equipment, and a controlled lab environment. In this study, we developed a loop-mediated isothermal amplification-lateral-flow-dipstick (LAMP-LFD) assay that specifically targets the 529 bp for detecting T. gondii infection. This novel portable device is universal, fast, user-friendly, and guarantees experimental sensitivity as well as low risk of aerosol contamination. Our LAMP-LFD assay has a detection limit of 1 fg of T. gondii DNA, and shows no cross-reaction with other parasitic pathogens, including Cryptosporidium parvum, Leishmania donovani, and Plasmodium vivax. We validated the developed assay by detecting T. gondii in DNA extracted from blood samples collected from 318 stray cats and dogs sampled from Deqing, Wenzhou, Yiwu, Lishui and Zhoushan cities across Zhejiang province, Eastern China. The LAMP-LFD device detected T. gondii DNA in 4.76 and 4.69% of stray cats and dogs, respectively. In conclusion, the developed LAMP-LFD assay is efficient, minimizes aerosol contamination, and is therefore suitable for detecting T. gondii across basic medical institutions and field settings.
Topics: Animals; Cats; China; Cryptosporidiosis; Cryptosporidium; Dogs; Molecular Diagnostic Techniques; Nucleic Acid Amplification Techniques; Sensitivity and Specificity; Toxoplasma
PubMed: 33944774
DOI: 10.1051/parasite/2021039 -
Journal of Veterinary Science Jan 2021Quantitation of urine protein is important in dogs with chronic kidney disease. Various analyzers are used to measure urine protein-to-creatinine ratios (UPCR). (Comparative Study)
Comparative Study
BACKGROUND
Quantitation of urine protein is important in dogs with chronic kidney disease. Various analyzers are used to measure urine protein-to-creatinine ratios (UPCR).
OBJECTIVES
This study aimed to compare the UPCR obtained by three types of analyzers (automated wet chemistry analyzer, in-house dry chemistry analyzer, and dipstick reading device) and investigate whether the differences could affect clinical decision process.
METHODS
Urine samples were collected from 115 dogs. UPCR values were obtained using three analyzers. Bland-Altman and Passing Bablok tests were used to analyze agreement between the UPCR values. Urine samples were classified as normal or proteinuria based on the UPCR values obtained by each analyzer and concordance in the classification evaluated with Cohen's kappa coefficient.
RESULTS
Passing and Bablok regression showed that there were proportional as well as constant difference between UPCR values obtained by a dipstick reading device and those obtained by the other analyzers. The concordance in the classification of proteinuria was very high (κ = 0.82) between the automated wet chemistry analyzer and in-house dry chemistry analyzer, while the dipstick reading device showed moderate concordance with the automated wet chemistry analyzer (κ = 0.52) and in-house dry chemistry analyzer (κ = 0.53).
CONCLUSIONS
Although the urine dipstick test is simple and a widely used point-of-care test, our results indicate that UPCR values obtained by the dipstick test are not appropriate for clinical use. Inter-instrumental variability may affect clinical decision process based on UPCR values and should be emphasized in veterinary practice.
Topics: Animals; Creatinine; Diagnostic Tests, Routine; Dog Diseases; Dogs; Female; Male; Proteinuria; Urinalysis
PubMed: 33522166
DOI: 10.4142/jvs.2021.22.e14 -
The Cochrane Database of Systematic... Jan 2015Urinary dipsticks are sometimes used for screening asymptomatic people, and for case-finding among inpatients or outpatients who do not have genitourinary symptoms.... (Review)
Review
BACKGROUND
Urinary dipsticks are sometimes used for screening asymptomatic people, and for case-finding among inpatients or outpatients who do not have genitourinary symptoms. Abnormalities identified on screening sometimes lead to additional investigations, which may identify serious disease, such as bladder cancer and chronic kidney disease (CKD). Urinary dipstick screening could improve prognoses due to earlier detection, but could also lead to unnecessary and potentially invasive follow-up testing and unnecessary treatment.
OBJECTIVES
We aimed to quantify the benefits and harms of screening with urinary dipsticks in general populations and patients in hospitals.
SEARCH METHODS
We searched the Cochrane Renal Group's Specialised Register to 8 September 2014 through contact with the Trials Search Co-ordinator using search terms relevant to this review.
SELECTION CRITERIA
Randomised controlled trials and other study types that compared urinary dipstick screening with no dipstick screening were eligible for inclusion. We searched for studies that investigated the use of urinary dipsticks for detecting haemoglobin, protein, albumin, albumin-creatinine ratio, leukocytes, nitrite, or glucose, alone or in any combination, and in any setting. We planned to exclude studies conducted in patients with urinary disorders.
DATA COLLECTION AND ANALYSIS
It was planned that two authors would independently extract data from included studies and assess risk of bias using the Cochrane risk of bias tool. However, no studies met our inclusion criteria.
MAIN RESULTS
Literature searches to 8 September 2014 yielded 4298 records, of which 4249 were excluded following title and abstract assessment. There were 49 records (44 studies) eligible for full text assessment; of these 18 studies were not RCTs and 26 studies compared interventions or controls that were not relevant to this review. Thus, no studies were eligible for inclusion.
AUTHORS' CONCLUSIONS
We found no evidence to assess the benefits and harms of screening with urinary dipsticks, which remain unknown.
Topics: Humans; Kidney Diseases; Reagent Kits, Diagnostic
PubMed: 25626128
DOI: 10.1002/14651858.CD010007.pub2 -
Trends in Biotechnology Dec 2017Lateral flow assays (LFAs) are highly attractive for point-of-care (POC) diagnostics for infectious disease, food safety, and many other medical uses. The unique... (Review)
Review
Lateral flow assays (LFAs) are highly attractive for point-of-care (POC) diagnostics for infectious disease, food safety, and many other medical uses. The unique optical, electronic, and chemical properties that arise from the nanostructured and material characteristics of nanoparticles provide an opportunity to increase LFA sensitivity and impart novel capabilities. However, interfacing to nanomaterials in complex biological environments is challenging and can result in undesirable side effects such as non-specific adsorption, protein denaturation, and steric hindrance. These issues are even more acute in LFAs where there are many different types of inorganic-biological interfaces, often of a complex nature. Therefore, the unique properties of nanomaterials for LFAs must be exploited in a way that addresses these interface challenges.
Topics: Antibodies; Antigens; Biosensing Techniques; Equipment Design; Humans; Immunoassay; Nanoparticles; Nanotechnology; Quantum Dots
PubMed: 28965747
DOI: 10.1016/j.tibtech.2017.09.001 -
MSphere May 2021Isothermal nucleic acid amplification tests (iNATs), such as loop-mediated isothermal amplification (LAMP), are good alternatives to PCR-based amplification assays,...
Isothermal nucleic acid amplification tests (iNATs), such as loop-mediated isothermal amplification (LAMP), are good alternatives to PCR-based amplification assays, especially for point-of-care and low-resource use, in part because they can be carried out with relatively simple instrumentation. However, iNATs can often generate spurious amplicons, especially in the absence of target sequences, resulting in false-positive results. This is especially true if signals are based on non-sequence-specific probes, such as intercalating dyes or pH changes. In addition, pathogens often prove to be moving, evolving targets and can accumulate mutations that will lead to inefficient primer binding and thus false-negative results. Multiplex assays targeting different regions of the analyte and logical signal readout using sequence-specific probes can help to reduce both false negatives and false positives. Here, we describe rapid conversion of three previously described SARS-CoV-2 LAMP assays that relied on a non-sequence-specific readout into individual and multiplex one-pot assays that can be visually read using sequence-specific oligonucleotide strand exchange (OSD) probes. We describe both fluorescence-based and Boolean logic-gated colorimetric lateral flow readout methods and demonstrate detection of SARS-CoV-2 virions in crude human saliva. One of the key approaches to treatment and control of infectious diseases, such as COVID-19, is accurate and rapid diagnostics that is widely deployable in a timely and scalable manner. To achieve this, it is essential to go beyond the traditional gold standard of quantitative PCR (qPCR) that is often faced with difficulties in scaling due to the complexity of infrastructure and human resource requirements. Isothermal nucleic acid amplification methods, such as loop-mediated isothermal amplification (LAMP), have been long pursued as ideal, low-tech alternatives for rapid, portable testing. However, isothermal approaches often suffer from false signals due to employment of nonspecific readout methods. We describe general principles for rapidly converting nonspecifically read LAMP assays into assays that are read in a sequence-specific manner by using oligonucleotide strand displacement (OSD) probes. We also demonstrate that inclusion of OSD probes in LAMP assays maintains the simplicity of one-pot assays and a visual yes/no readout by using fluorescence or colorimetric lateral-flow dipsticks while providing accurate sequence-specific readout and the ability to logically query multiplex amplicons for redundancy or copresence. These principles not only yielded high-surety isothermal assays for SARS-CoV-2 but might also aid in the design of more sophisticated molecular assays for other analytes.
Topics: COVID-19; COVID-19 Testing; Humans; Molecular Diagnostic Techniques; Nucleic Acid Amplification Techniques; Point-of-Care Testing; RNA, Viral; SARS-CoV-2; Saliva
PubMed: 34011690
DOI: 10.1128/mSphere.00911-20 -
Biosensors Dec 2023Ketones are well-known biomarkers of fat oxidation produced in the liver as a result of lipolysis. These biomarkers include acetoacetic acid and β-hydroxybutyric acid...
Ketones are well-known biomarkers of fat oxidation produced in the liver as a result of lipolysis. These biomarkers include acetoacetic acid and β-hydroxybutyric acid in the blood/urine and acetone in our breath and skin. Monitoring ketone production in the body is essential for people who use caloric intake deficit to reduce body weight or use ketogenic diets for wellness or therapeutic treatments. Current methods to monitor ketones include urine dipsticks, capillary blood monitors, and breath analyzers. However, these existing methods have certain disadvantages that preclude them from being used more widely. In this work, we introduce a novel acetone sensor device that can detect acetone levels in breath and overcome the drawbacks of existing sensing approaches. The critical element of the device is a robust sensor with the capability to measure acetone using a complementary metal oxide semiconductor (CMOS) chip and convenient data analysis from a red, green, and blue deconvolution imaging approach. The acetone sensor device demonstrated sensitivity of detection in the micromolar-concentration range, selectivity for detection of acetone in breath, and a lifetime stability of at least one month. The sensor device utility was probed with real tests on breath samples using an established blood ketone reference method.
Topics: Humans; Acetone; Body Fluids; Ketones; 3-Hydroxybutyric Acid; Biomarkers
PubMed: 38248381
DOI: 10.3390/bios14010004 -
Health Technology Assessment... Mar 2009To estimate clinical and dipstick predictors of infection and develop and test clinical scores; to compare management using clinical and dipstick scores with commonly... (Review)
Review
Dipsticks and diagnostic algorithms in urinary tract infection: development and validation, randomised trial, economic analysis, observational cohort and qualitative study.
OBJECTIVES
To estimate clinical and dipstick predictors of infection and develop and test clinical scores; to compare management using clinical and dipstick scores with commonly used alternative strategies; to estimate the cost-effectiveness of each strategy; and to understand the natural history of urinary tract infection (UTI) and women's concerns about its presentation and management.
DESIGN
There were six studies: (1) validation development for diagnostic clinical and dipstick scores; (2) validation of the scores developed; (3) observation of the natural history of UTI; (4) randomised controlled trial (RCT) of scores developed in study 1; (5) economic analysis of the RCT; (6) qualitative study of patients in the RCT.
SETTING
Primary care.
PARTICIPANTS
Women aged 17-70 with suspected UTI.
INTERVENTIONS
Patients were randomised to five management approaches: empirical antibiotics; empirical delayed antibiotics; target antibiotics based on a higher symptom score; target antibiotics based on dipstick results; or target antibiotics based on a positive mid-stream specimen of urine (MSU).
MAIN OUTCOME MEASURES
Antibiotic use, use of MSUs, rates of reconsultation and duration, and severity of symptoms.
RESULTS
(1) 62.5% of women had confirmed UTI. Only nitrite, leucocyte esterase and blood independently predicted diagnosis of UTI. A dipstick rule--based on having nitrite or both leucocytes and blood--was moderately sensitive (77%) and specific (70%) [positive predictive value (PPV) 81%, negative predictive value (NPV) 65%]. A clinical rule--based on having two of urine cloudiness, offensive smell, reported moderately severe dysuria, moderately severe nocturia--was less sensitive (65%) (specificity 69%, PPV 77%, NPV 54%). (2) 66% of women had confirmed UTI. The predictive values of nitrite, leucocyte esterase and blood were confirmed. The dipstick rule was moderately sensitive (75%) but less specific (66%) (PPV 81%, NPV 57%). (3) Symptoms rated as moderately bad or worse lasted 3.25 days on average for infections sensitive to antibiotics; resistant infections lasted 56% longer, infections not treated with antibiotics 62% longer and symptoms associated with urethral syndrome 33% longer. Symptom duration was shorter if the doctor was perceived to be positive about prognosis, and longer with frequent somatic symptoms, previous history of cystitis, urinary frequency and more severe symptoms at baseline. (4) 66% of the MSU group had laboratory-confirmed UTI. Women suffered 3.5 days of moderately bad symptoms if they took antibiotics immediately but 4.8 days if they delayed taking antibiotics for 48 hours. Taking bicarbonate or cranberry juice had no effect. (5) The MSU group was more costly over 1 month but not over 1 year. Cost-effectiveness acceptability curves showed that for a value per day of moderately bad symptoms of over 10 pounds, the dipstick strategy is most likely to be cost-effective. (6) Fear of spread to the kidneys, blood in the urine, and the impact of symptoms on vocational and leisure activities were important triggers for seeking help. When patients are asked to delay taking antibiotics the uncomfortable and worrying journey from 'person to patient' needs to be acknowledged and the rationale behind delaying the antibiotics made clear.
CONCLUSIONS
To achieve good symptom control and reduce antibiotic use clinicians should either offer a 48-hour delayed antibiotic prescription to be used at the patient's discretion or target antibiotic treatment by dipsticks (positive nitrite or positive leucocytes and blood) with the offer of a delayed prescription if dipstick results are negative.
Topics: Algorithms; Anti-Bacterial Agents; Attitude to Health; Cohort Studies; Cost-Benefit Analysis; Decision Trees; Female; Humans; Patient Selection; Practice Patterns, Physicians'; Predictive Value of Tests; Primary Health Care; Qualitative Research; Randomized Controlled Trials as Topic; Reagent Strips; Reproducibility of Results; Research Design; Severity of Illness Index; Time Factors; Urinary Tract Infections; Women
PubMed: 19364448
DOI: 10.3310/hta13190 -
Clinica Chimica Acta; International... Aug 2023To address the situation that the accuracy of concentration intervals (CI) corresponding to dipstick grades is not given by the manufacturers or literature, we developed...
BACKGROUND
To address the situation that the accuracy of concentration intervals (CI) corresponding to dipstick grades is not given by the manufacturers or literature, we developed a method that determined reasonable dipstick grades with concentration intervals (GCIs) based on the percent agreement (PA) and discussed the GCI application to comparability among currently dipstick tests.
METHODS
By comparing the results of 2 dipstick tests (iChem and KU-500) with the quantitative test (AU5800), the GCIs were verified and established based on the PAs, which were calculated and used as an indicator of GCI's accuracy. The overlap (percent) between the 2 GCIs with the same grade (2 dipstick devices), was calculated and used to evaluate the agreement between their test results.
RESULTS
After verification and adjustment, the GCI and PA combinations for iChem Velocity were as follows: - (<0.1 g/l, 85 %), ± (0.1-0.3 g/l, 66 %), 1+ (0.3-1 g/l, 78 %), 2+ (1-3 g/l, 74 %), 3+ (3-6 g/l, 77 %), and 4+ (≥6 g/l, 84 %). The determined GCI and PA combinations for KU-500 were: - (<0.1.2 g/l, 75 %), ± (0.12-0.5 g/l, 63 %), 1+ (0.5-1.2 g/l, 69 %), 2+ (1.2-3.2 g/l, 76 %), and 3+ (≥3.2 g/l, 82 %). The GCI overlaps between the 2 dipstick devices were - (83 %), ± (45 %), 1+ (56 %), 2+ (82 %), and 3+ or ≥3+ (94 %). The overall overlap was 72 %. Since the overlaps ± (45 %) and 1+ (56 %) were within the overlap reject limit for any grade (70 %), and the overall overlap (72 %) was within the overall overlap reject limit (80 %), the test results of the 2 devices were not comparable.
CONCLUSIONS
GCIs can be verified and established correctly based on PAs, and industry standards for dipstick tests can be established based on GCIs and PAs. Comparability between dipstick devices, historical data, and literature data can be roughly determined based on the overlap.
Topics: Humans; Sensitivity and Specificity; Urinalysis; Reagent Strips
PubMed: 37500032
DOI: 10.1016/j.cca.2023.117500