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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 -
BMC Nephrology Jun 2021Most studies of chronic kidney disease (CKD) in Sub-Saharan Africa (SSA) have been conducted in urban settings. They relied on GFR estimated from serum creatinine alone...
BACKGROUND
Most studies of chronic kidney disease (CKD) in Sub-Saharan Africa (SSA) have been conducted in urban settings. They relied on GFR estimated from serum creatinine alone and on the inexpensive, convenient urinary dipstick to assess proteinuria. The dipstick for proteinuria has not been directly compared with the gold standard albumin-to-creatinine ratio (ACR) in a large-sized study in SSA. We hereby assessed the influence of rural versus urban location on the level, interpretation, and diagnostic performance of proteinuria dipstick versus ACR.
METHODS
In a cross-sectional population-based study of CKD in both urban (n = 587) and rural (n = 730) settings in South-Kivu, Democratic Republic of Congo (DRC), we assessed the prevalence, performance (sensitivity, specificity, positive predictive value and negative predictive value) and determinants of a positive dipstick proteinuria as compared with albuminuria (ACR). Albuminuria was subdivided into: A1 (< 30 mg/g creatinine), A2 (30 to 299 mg/g creatinine) and A3 (≥ 300 mg/g creatinine).
RESULTS
The overall prevalence of positive dipstick proteinuria (≥ 1+) was 9.6 % (95 % CI, 7.9-11.3) and was higher in rural than in urban residents (13.1 % vs. 4.8 %, p < 0.001), whereas the prevalence of albuminuria (A2 or A3) was similar in both sites (6 % rural vs. 7.6 % urban, p = 0.31). In both sites, dipstick proteinuria ≥ 1 + had a poor sensitivity (< 50 %) and positive predictive value (< 11 %) for the detection of A2 or A3. The negative predictive value was 95 %. Diabetes [aOR 6.12 (1.52-24.53)] was a significant predictor of A3 whereas alkaline [aOR 7.45 (3.28-16.93)] and diluted urine [aOR 2.19 (1.35-3.57)] were the main predictors of positive dipstick proteinuria.
CONCLUSIONS
ACR and dipstick proteinuria have similar positivity rates in the urban site whereas, in the rural site, dipstick was 2-fold more often positive than ACR. The poor sensitivity and positive predictive value of the dipstick as compared with ACR makes it unattractive as a screening tool in community studies of CKD in SSA.
Topics: Adult; Creatinine; Cross-Sectional Studies; Democratic Republic of the Congo; Female; Glomerular Filtration Rate; Humans; Hydrogen-Ion Concentration; Male; Predictive Value of Tests; Proteinuria; Reagent Strips; Renal Insufficiency, Chronic; Rural Health; Urban Health; Urine
PubMed: 34172013
DOI: 10.1186/s12882-021-02431-w -
Clinical Microbiology and Infection :... Feb 2022Cholera is an acute diarrheal disease caused by Vibrio cholerae O1 or O139. Cholera rapid diagnostic tests (RDTs) are widely used to screen for cholera cases. However,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cholera is an acute diarrheal disease caused by Vibrio cholerae O1 or O139. Cholera rapid diagnostic tests (RDTs) are widely used to screen for cholera cases. However, their accuracy has not been systematically reviewed.
OBJECTIVES
To evaluate the diagnostic accuracy of cholera RDTs.
METHODS
Systematic review and meta-analysis.
DATA SOURCES
Medline, EMBASE and Web of science through to November 2020; references of included studies and a technical guidance on cholera RDTs. This review is registered with PROSPERO (CRD42021233124).
STUDY ELIGIBILITY CRITERIA
Cross-sectional studies comparing the performance of cholera RDTs either to stool culture or PCR.
PARTICIPANTS
Individuals with clinically suspected cholera.
DATA EXTRACTION
Two authors independently extracted data and assessed the quality using Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) criteria.
RESULTS
Eighteen studies were included in the systematic review of which 17 were used for meta-analysis. Crystal VC was the most frequently used RDT (13 studies), followed by Cholkit and Institut Pasteur cholera dipstick (three studies each), SD Bioline (two studies), Artron (one study) and Smart (one study). Using direct testing (n = 12 627 specimens), the bivariate random-effects model yielded a pooled sensitivity and specificity of 91% (95% CI 87%-94%) and 80% (95% CI 74%-84%), respectively. However, through alkaline peptone water (APW) enrichment (n = 3403 specimens), the pooled sensitivity and specificity were 89% (95% CI 79%-95%) and 98% (95% CI 95%-99%), respectively.
CONCLUSION
Cholera RDTs, especially when enriched with APW, have moderate sensitivity and specificity. Although less useful for clinical management, the current generation of RDTs have clear utility for surveillance efforts if used in a principled manner. Enrichment of stool specimens in APW before using cholera RDTs reduces the possibility of obtaining false-positive results, despite the few cholera cases that go undetected. It is noteworthy that APW-enriched cholera RDTs are not necessarily rapid tests, and are not listed in the Global Task Force on Cholera Control/WHO target product profile.
Topics: Cholera; Cross-Sectional Studies; Humans; Reagent Kits, Diagnostic; Sensitivity and Specificity; Vibrio cholerae O1
PubMed: 34506946
DOI: 10.1016/j.cmi.2021.08.027 -
Australian Family Physician Nov 2005Urinary abnormalities are commonly detected in children and can be due to a wide range of conditions. (Review)
Review
BACKGROUND
Urinary abnormalities are commonly detected in children and can be due to a wide range of conditions.
OBJECTIVE
This article provides an overview of common urinary abnormalities presenting in childhood to assist general practitioners in planning further investigation and management.
DISCUSSION
An initial assessment based upon a comprehensive history, examination and urinalysis should ensure that serious conditions are not overlooked and that unnecessary laboratory studies are not performed. Urinary dipstick testing should not be used to diagnose a urinary tract infection, but can often be used as a screen to exclude one. Isolated microscopic haematuria is only rarely a sign of significant kidney or urinary tract disease and nonpostural proteinuria is a more important diagnostic and prognostic finding that requires specialist assessment. In the majority of cases, the family can be reassured that the risk of significant kidney disease in asymptomatic children with minor urinary abnormalities is small.
Topics: Child; Child, Preschool; Family Practice; Female; Hematuria; Humans; Infant; Male; Nephrotic Syndrome; Predictive Value of Tests; Proteinuria; Urinalysis; Urinary Tract Infections; Urologic Diseases
PubMed: 16299627
DOI: No ID Found -
Journal of Epidemiology Jan 2021Previous studies have suggested the potential association between renal diseases and gallstone. The extent of proteinuria is recognized as a marker for the severity of...
BACKGROUND
Previous studies have suggested the potential association between renal diseases and gallstone. The extent of proteinuria is recognized as a marker for the severity of chronic kidney disease. However, little data is available to identify the risk of incident gallstone according to the level of proteinuria.
METHODS
Using a data of 207,356 Koreans registered in National Health Insurance Database, we evaluated the risk of gallstone according to the levels of urine dipstick proteinuria through an average follow-up of 4.36 years. Study subjects were divided into 3 groups by urine dipstick proteinuria (negative: 0, mild: 1+ and heavy: 2+ or greater). Multivariate Cox-proportional hazard model was used to assess the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident cholelithiasis according to urine dipstick proteinuria.
RESULTS
The group with higher urine dipstick proteinuria had worse metabolic, renal, and hepatic profiles than those without proteinuria, which were similarly observed in the group with incident cholelithiasis. The heavy proteinuria group had the greatest incidence of cholelithiasis (2.39%), followed by mild (1.54%) and negative proteinuria groups (1.39%). Analysis for multivariate Cox-proportional hazard model indicated that the heavy proteinuria group had higher risk of cholelithiasis than other groups (negative: reference, mild proteinuria: HR 0.97 [95% CI, 0.74-1.26], and heavy proteinuria: HR 1.46 [95% CI, 1.09-1.96]).
CONCLUSION
Urine dipstick proteinuria of 2+ or greater was significantly associated with increased risk for incident gallstone.
Topics: Adult; Biomarkers; Cholelithiasis; Databases, Factual; Female; Gallstones; Glomerular Filtration Rate; Humans; Incidence; Male; Middle Aged; Predictive Value of Tests; Proteinuria; Republic of Korea; Risk Factors; Urinalysis
PubMed: 31956168
DOI: 10.2188/jea.JE20190223 -
Neurourology and Urodynamics Apr 2017Antibiotic prophylaxis before urodynamic testing (UDS) is widely utilized to prevent urinary tract infection (UTI) with only limited guidance. The Society of... (Review)
Review
AIMS
Antibiotic prophylaxis before urodynamic testing (UDS) is widely utilized to prevent urinary tract infection (UTI) with only limited guidance. The Society of Urodynamics, Female Pelvic Medicine, and Urogenital Reconstruction (SUFU) convened a Best Practice Policy Panel to formulate recommendations on the urodynamic antibiotic prophylaxis in the non-index patient.
METHODS
Recommendations are based on a literature review and the Panel's expert opinion, with all recommendations graded using the Oxford grading system.
RESULTS
All patients should be screened for symptoms of UTI and undergo dipstick urinalysis. If the clinician suspects a UTI, the UDS should be postponed until it has been treated. The first choice for prophylaxis is a single oral dose of trimethoprim-sulfamethoxazole before UDS, with alternative antibiotics chosen in case of allergy or intolerance. Individuals who do NOT require routine antibiotic prophylaxis include those without known relevant genitourinary anomalies, diabetics, those with prior genitourinary surgery, a history of recurrent UTI, post-menopausal women, recently hospitalized patients, patients with cardiac valvular disease, nutritional deficiencies or obesity. Identified risk factors that increase the potential for UTI following UDS and for which the panel recommends peri-procedure antibiotics include: known relevant neurogenic lower urinary tract dysfunction, elevated PVR, asymptomatic bacteriuria, immunosuppression, age over 70, and patients with any indwelling catheter, external urinary collection device, or performing intermittent catheterization. Patients with orthopedic implants have a separate risk stratification.
CONCLUSIONS
These recommendations can assist urodynamic providers in the appropriate use of antibiotics for UDS testing. Clinical judgment of the provider must always be considered.
Topics: Antibiotic Prophylaxis; Diagnostic Techniques, Urological; Humans; Practice Guidelines as Topic; Urinary Tract Infections; Urodynamics
PubMed: 28345769
DOI: 10.1002/nau.23253 -
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 -
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 -
Malaria Journal Nov 2015Isothermal amplification techniques are emerging as a promising method for malaria diagnosis since they are capable of detecting extremely low concentrations of parasite...
BACKGROUND
Isothermal amplification techniques are emerging as a promising method for malaria diagnosis since they are capable of detecting extremely low concentrations of parasite target while mitigating the need for infrastructure and training required by other nucleic acid based tests. Recombinase polymerase amplification (RPA) is promising for further development since it operates in a short time frame (<30 min) and produces a product that can be visually detected on a lateral flow dipstick. A self-sealing paper and plastic system that performs both the amplification and detection of a malaria DNA sequence is presented.
METHODS
Primers were designed using the NCBI nBLAST tools and screened using gel electrophoresis. Paper and plastic devices were prototyped using commercial design software and parts were cut using a laser cutter and assembled by hand. Synthetic copies of the Plasmodium 18S gene were spiked into solution and used as targets for the RPA reaction. To test the performance of the device the same samples spiked with synthetic target were run in parallel both in the paper and plastic devices and using conventional bench top methods.
RESULTS
Novel RPA primers were developed that bind to sequences present in the four species of Plasmodium which infect humans. The paper and plastic devices were found to be capable of detecting as few as 5 copies/µL of synthetic Plasmodium DNA (50 copies total), comparable to the same reaction run on the bench top. The devices produce visual results in an hour, cost approximately $1, and are self-contained once the device is sealed.
CONCLUSIONS
The device was capable of carrying out the RPA reaction and detecting meaningful amounts of synthetic Plasmodium DNA in a self-sealing and self-contained device. This device may be a step towards making nucleic acid tests more accessible for malaria detection.
Topics: Costs and Cost Analysis; DNA, Protozoan; DNA, Ribosomal; Equipment and Supplies; Humans; Malaria; Molecular Diagnostic Techniques; Nucleic Acid Amplification Techniques; Paper; Plasmodium; Plastics; RNA, Ribosomal, 18S; Time Factors
PubMed: 26611141
DOI: 10.1186/s12936-015-0995-6 -
Lab on a Chip Feb 2019Influenza is a viral respiratory tract infection responsible for up to 5 million cases of severe infection and nearly 600 000 deaths worldwide each year. While...
Influenza is a viral respiratory tract infection responsible for up to 5 million cases of severe infection and nearly 600 000 deaths worldwide each year. While treatments for influenza exist, diagnostics for the virus at the point of care are limited in their sensitivity and ability to differentiate between subtypes. We have developed an integrated two-dimensional paper network (2DPN) for the detection of the influenza virus by the surface glycoprotein, hemagglutinin. The hemagglutinin assay was developed using proteins computationally designed to bind with high affinity to the highly-conserved sialic acid binding site. The integrated 2DPN uses a novel geometry that allows automated introduction of an enzymatic amplification reagent directly to the detection zone. This assay was integrated into a prototype device and demonstrated successful detection of clinically relevant virus concentrations spiked into 70 μL of virus-free pediatric nasal swab samples. Using this novel geometry, we found improved assay performance on the device (compared to a manually-operated dipstick method), with a sensitivity of 4.45 × 102 TCID50 per mL on device.
Topics: Hemagglutinin Glycoproteins, Influenza Virus; Humans; Influenza, Human; Molecular Diagnostic Techniques; Paper; Point-of-Care Systems
PubMed: 30724293
DOI: 10.1039/c8lc00691a