EXPRESS: Negative values and variance functions: Implications for statistical analysis

2020 ◽  
pp. 000456322098554
Author(s):  
William Sadler
Keyword(s):  
Clinical Practice ◽  
Statistical Analysis ◽  
Data Reduction ◽  
Limit Of Detection ◽  
Limit Of Quantification ◽  
Reporting Practices ◽  
Negative Results ◽  
Variance Functions

Abstract When reporting concentrations of substances in biological specimens it has been virtually universal practice to suppress negative results, initially by left-censoring negative results to zero and more recently by left-censoring to values such as Limit of Blank (LoB), Limit of Detection (LoD) or even Limit of Quantification (LoQ). Negative concentrations are obviously nonsensical and current reporting practices place proper emphasis on assisting the clinician. However, it is easily overlooked that negative concentrations are merely artefacts of data reduction and while adjusting them is sensible clinical practice there are potentially adverse consequences for statistical analysis, in particular for those parametric summaries and analyses which rely on reliable estimates of low-end uncertainty. This article puts a case for the availability of negative results, describes complications with respect to estimating variance functions and discusses practical workarounds.

scholarly journals Faecal immunochemical testing (FIT): Sources of analytical variation based on three years of routine testing in the context of DG30

2020 ◽  
Author(s):  
Tim James ◽  
Brian D Nicholson ◽  
Rhiannon Marr ◽  
Maria Paddon ◽  
James E East ◽  
...  
Keyword(s):  
Primary Care ◽  
Limit Of Detection ◽  
Care Practice ◽  
Limit Of Quantification ◽  
Cancer Symptoms ◽  
Negative Results ◽  
Independent Verification ◽  
Nice Guidance ◽  
Primary Care Patients ◽  
Immunochemical Test

AbstractAimsTo determine analytical capabilities of a commonly used faecal immunochemical test (FIT) to detect haemoglobin (Hb) in the context of NICE guidance DG30, and the likely use of FIT to reprioritise patients delayed by the COVID-19 pandemic.MethodsData obtained from independent verification studies and clinical testing of the HM-JACKarc FIT method in routine primary care practice were analysed to derive analytical performance characteristics.ResultsDetection capabilities for the FIT method were 0.5 µg/g (limit of blank), 1.1 (limit of detection) and 15.0 µg/g (limit of quantification). 31 of 33 (94%) non-homogenised specimens analysed in triplicate were consistently categorised relative to 10 µg/g compared to all 33 (100%) homogenised specimens. Imprecision in non-homogenised specimens was higher (median 27.8%, (range 20.5% - 48.6%)) than in homogenised specimens (10.2%, (7.0 to 13.5%)). Considerable variation was observed in sequential clinical specimens from individual patients but no positive or negative trend in specimen degradation was observed (p=0.26).ConclusionsThe FIT method is capable of detecting Hb at concentrations well below the DG30 threshold of 10 µg/g. However, total imprecision is considerable when including sampling variation. Binary categorisation against a single defined threshold above and below 10 µg/g was more consistent and improved following specimen homogenisation. This approach may be more appropriate when reporting results for symptomatic patients tested in primary care, including those who have had definitive investigation delayed by the COVID-19 pandemic and need to be re-prioritised.Key MessagesFaecal immunochemical testing (FIT) is increasingly used to detect blood at low haemoglobin (Hb) concentrations in specimens from symptomatic primary care patients but the analytical characteristics in this context have not been fully documented.A commonly used FIT method showed good capability in a routine UK clinical setting to detect Hb at the NICE recommended threshold of 10µg/g. Imprecision estimates were considerable when sampling was considered, even above the limit of quantification of 15 µg/g.Analytical variability appears too high for reliable reporting of quantitative Hb concentrations: reporting positive or negative results around a threshold of 10µg/g appears more appropriate after sample homogenisation.Dichotomous FIT reporting is likely to be an important tool to risk stratify patients with lower GI cancer symptoms who have had their test deferred due to the COVID-19 pandemic

scholarly journals Cardiac Troponin Assays: Guide to Understanding Analytical Characteristics and Their Impact on Clinical Care

2017 ◽  
Vol 63 (1) ◽  
pp. 73-81 ◽  
Author(s):  
Fred S Apple ◽  
Yader Sandoval ◽  
Allan S Jaffe ◽  
Jordi Ordonez-Llanos
Keyword(s):  
Clinical Practice ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Limit Of Detection ◽  
Troponin T ◽  
Clinical Care ◽  
High Sensitivity ◽  
Reference Population ◽  
Limit Of Quantification ◽  
Coronary Syndrome

Abstract BACKGROUND Cardiac troponin I (cTnI) and cardiac troponin T (cTnT) determinations are fixtures in clinical practice and research. Cardiac troponin testing has been the standard of practice for the diagnosis of acute myocardial infarction (AMI), early rule-out, risk stratification, and outcomes assessment in patients presenting with acute coronary syndrome (ACS) and non-ACS myocardial injury. We recognize from reading the literature over the past several years how poorly understood the analytical characteristics are for cTnI and cTnT assays by laboratorians, clinicians, and scientists who use these assays. CONTENT The purposes of this mini-review are (a) to define limit of blank, limit of detection, limit of quantification, and imprecision, (b) overview the analytical characteristics of the existing cardiac troponin assays, (c) recommend approaches to define a healthy (normal) reference population for determining the 99th percentile and the appropriate statistic to use for this calculation, (d) clarify how an assay becomes designated as “high sensitivity,” and (e) provide guidance on determining delta (Δ) change values. SUMMARY This review raises important educational information regarding cTnI and cTnT assays, their 99th percentile upper reference limits (URL) differentiated by sex, and specifically addresses high-sensitivity (hs)-assays used to measure low concentrations. Recommendations are made to help clarify the nomenclature and analytical and clinical characteristics to define hs-assays. The review also identifies challenges for the evolving implementation of hs-assays into clinical practice. It is hoped that with the introduction of these concepts, laboratorians, clinicians and researchers can develop a more unified view of how these assays should be used worldwide.

scholarly journals Determination of cholesterol in human serum by an enzymatic method with the application of daos reagent

2000 ◽  
Vol 65 (7) ◽  
pp. 473-479
Author(s):  
Milena Jelikic-Stankov ◽  
Dejan Stankov ◽  
Snezana Paunovic
Keyword(s):  
Clinical Practice ◽  
Human Serum ◽  
Free Cholesterol ◽  
Limit Of Detection ◽  
Enzymatic Method ◽  
Limit Of Quantification ◽  
Experimental Conditions ◽  
Relative Standard ◽  
Influence Of Ph

A sensitive and specific enzymatic method has been developed for the determination of the total and free cholesterol in human serum based on the application of the newly-synthesized N-ethyl-N-(2-hydroxy-3-sulfopropyl)-3,5-dimethoxyaniline, (DAOS) Trinder's reagent. Using the proposed method, cholesterol could be determined in the concentration range of 0.15 mmol/L with a relative standard deviation of up to 1.1%. In order to find the optimal experimental conditions for the application of the DAOS reagent, the influence of its concentration on the linearity of the method, the influence of pH, as well as the influence of the activities of cholesterolesterase and cholesteroloxidase were examined. The obtained results of the determination of the total and free cholesterol were compared to the results obtained by the application of the most frequently employed enzymatic method in clinical practice, based on phenol as a reagent. The sensitivity of the method was 0.070 A/mmol/L, the limit of detection DL=0.03 mmol/L and the limit of quantification QL=0.09 mmol/L of cholesterol.

scholarly journals Total polyphenols from Syzygium cumini (L.) Skeels fruit extract

2009 ◽  
Vol 45 (1) ◽  
pp. 121-126 ◽  
Author(s):  
Ketylin Fernanda Migliato ◽  
Elisângela Simões de Carvalho ◽  
Luis Vitor Silva do Sacramento ◽  
João Carlos Palazzo de Mello ◽  
André Rolim Baby ◽  
...  
Keyword(s):  
Statistical Analysis ◽  
Spectrophotometric Method ◽  
Limit Of Detection ◽  
Low Cost ◽  
Syzygium Cumini ◽  
Fruit Extract ◽  
Total Polyphenols ◽  
Limit Of Quantification ◽  
Pyrogallic Acid

A precise, accurate and low cost spectrophotometric method was developed and validated for routine determination of total polyphenols, as pyrogallic acid equivalents, from the percolated and lyophilized extract of Syzygium cumini (L.) Skeels fruits. Validation was assessed experimentally and data were rigorously treated by statistical analysis. Analytical parameters were: linearity, interval (range), precision and recovery/accuracy, limit of detection (LOD, μg mL-1) and limit of quantification (LOQ, μg mL-1). The visible spectrophotometric method presented linearity (r² = 0.9979 ± 0.0010) over the concentration range 0.25-7.5 μg mL-1 of standard pyrogallic acid, precision < 2.918171%, recovery/accuracy ranging from 96.228693 to 107.17701%, LOD = 0.21 μg mL-1 and LOQ = 0.64 μg mL-1.

Spectrophotometeric Determination of Trifluoperazine HCL in Pure Forms and Pharmaceutical Preperations

2017 ◽  
Vol 9 (5) ◽  
Author(s):  
Mohammad Hamzah Hamzah ◽  
Rawa M M Taqi ◽  
Muna M. Hasan ◽  
Raid J. M. Al-Timimi
Keyword(s):  
Standard Method ◽  
Limit Of Detection ◽  
Molar Absorptivity ◽  
Dosage Forms ◽  
Oxidizing Agent ◽  
Optimum Conditions ◽  
Limit Of Quantification ◽  
Cerium Ion ◽  
Blank Solution

A simple and accurate spectrophotometric method for the determination of Trifluoperazine HCl in pure and dosage forms was developed. The method is based on the reaction between Trifluoperazine HCl and p-chloroaniline in the presence of cerium ion as oxidizing agent which lead to the formation of violate color product that absorbed at a maximum wavelength 570nm while the blank solution was pink. Under the optimum conditions a linear relationship between the intensity and concentration of TRF in the range 4-50μg/ml was obtained . The molar absorptivity 3.74×103 L.mol-1.cm-1 , Limit of detection (2.21μg/ml), while limit of quantification was 7.39μg/ml. The proposed analytical method was compared with standard method using t-test and F-test , the obtained results shows there is no significant differences between proposed method and standard method. Based on that the proposed method can be used as an alternative method for the determination of TRF in pure and dosage forms.

Recent Trends in Development of Nanomaterials Based Green Analytical Methods for Environmental Remediation

2020 ◽  
Vol 16 ◽  
Author(s):  
Sidra Amin ◽  
Amber R. Solangi ◽  
Dilawar Hassan ◽  
Nadir Hussain ◽  
Jamil Ahmed ◽  
...  
Keyword(s):  
Optical Sensors ◽  
Environmental Remediation ◽  
Environmental Chemistry ◽  
Limit Of Detection ◽  
Environmental Pollutants ◽  
Toxic Metal ◽  
Electrochemical Analysis ◽  
Good Choice ◽  
Nano Materials ◽  
Limit Of Quantification

Background: In recent years, the occurrence and fate of environmental pollutants has been recognized as one of the emerging issues in environmental chemistry. A survey documented about a wide variety of these pollutants, which are often detected in our environment and these are major cause of shortened life spans and the global warming. These pollutants include toxic metal, pesticides, fertilizers, drugs and dyes released into soil and major water bodies. The presence of these contaminants causes major disturbance in eco-system’s balance. To tackle these issues many technological improvements are made to detect minute contaminations. The latest issue being answered by the scientists is the use of green nano materials as sensors which are economical, instant and give much better results at low concentrations and can be used for the field measurements resulting in no dangerous by-product that could lead to more environmental contamination. Nano materials are known for their wide band gap, enhanced physical and optical properties with option of tuneablity as per need, by optimizing certain parameters. They are proved to be good choice for analytical/optical sensors with high sensitivity. Objective: This review holds information about multiple methods that use green nanomaterials for the analytical assessment of environmental pollutants. UV-Vis spectrophotometry and electrochemical analysis using green and reproducible nanomaterials are the major focus of this review article. To date, there are number of spectrophotometric and electro chemical methods available that have been used for the detection of environmental pollutants such as toxic metals, pesticides and dyes. Conclusion: The use of nanomaterials can drastically change the detection limits due to having large surface area, strong catalytic properties, and tunable possibility. With the use of nano materials, lower than the marked limit of detection and limit of quantification were seen when compared with previously reported work. The used nano-materials could be washed, dried, and reused, which makes the methods more proficient, cost effective and environmentally friendly.

Calcium/Copper alginate framework doped with CuO nano-particles as a novel adsorbent for micro-extraction of benzodiazepines from human serum

2020 ◽  
Vol 16 ◽  
Author(s):  
Nadereh Rahbar ◽  
Fatemeh Ahmadi ◽  
Zahra Ramezani ◽  
Masoumeh Nourani
Keyword(s):  
Human Serum ◽  
High Performance ◽  
Limit Of Detection ◽  
Solid Phase ◽  
Nano Particles ◽  
Limit Of Quantification ◽  
Analytical Methodology ◽  
Fiber Fabrication ◽  
Relative Standard ◽  
Green Procedure

Background: Sample preparation is one of the most challenging phases in pharmaceutical analysis, especially in biological matrices, affecting the whole analytical methodology. Objective: In this study, a new Ca(II)/Cu(II)/alginate/CuO nanoparticles hydrogel fiber (CCACHF) was synthesized through a simple, green procedure and applied for fiber micro solid phase extraction (FMSPE) of diazepam (DIZ) and oxazepam (OXZ) as model drugs prior to high-performance liquid chromatography-UV detection (HPLC-UV). Methods: Composition and morphology of the prepared fiber were characterized and the effect of main parameters on the fiber fabrication and extraction efficiency have been studied and optimized. Results: In optimal conditions, calibration curves were linear ranging between 0.1–500 µg L−1 with regression coefficients of 0.9938 and 0.9968. Limit of detection (LOD) (S/N=3) and limit of quantification (LOQ) (S/N=10) of the technique for DIZ and OXZ were 0.03 to 0.1 µg L−1. Within-day and between-day relative standard deviations (RSDs) for DIZ and OXZ were 6.0–12.5% and 3.3–9.4%, respectively. Conclusion: The fabricated adsorbent has been substantially employed to extraction of selected benzo-diazepines (BZDs) from human serum real specimens and the obtained recoveries were also satisfactory (82.1-109.7%).

Eco-Friendly Green Liquid Chromatographic Separations of a Novel Combination of Azelastine and Fluticasone in the Presence of their Pharmaceutical Dosage form Additives

2020 ◽  
Vol 16 (3) ◽  
pp. 277-286
Author(s):  
Amal A. El-Masry ◽  
Mohammed E. A. Hammouda ◽  
Dalia R. El-Wasseef ◽  
Saadia M. El-Ashry
Keyword(s):  
Lower Limit ◽  
Dosage Form ◽  
Limit Of Detection ◽  
Sodium Dodecyl ◽  
Uv Detection ◽  
Simultaneous Estimation ◽  
Limit Of Quantification ◽  
Chromatographic Separations ◽  
Pharmaceutical Dosage Form ◽  
Liquid Chromatographic

Background: The first highly sensitive, rapid and specific green microemulsion liquid chromatographic (MELC) method was established for the simultaneous estimation of fluticasone propionate (FLU) and azelastine HCl (AZL) in the presence of their pharmaceutical dosage form additives (phenylethyl alcohol (PEA) and benzalkonium chloride (BNZ)). Methods: The separation was performed on a C18 column using (o/w) microemulsion as a mobile phase which contains 0.2 M sodium dodecyl sulphate (SDS) as surfactant, 10% butanol as cosurfactant, 1% n-octanol as internal phase and 0.3% triethylamine (TEA) adjusted at pH 6 by 0.02 M phosphoric acid; with UV detection at 220 nm and programmed with flow rate of 1 mL/min. Results: The validation characteristics e.g. linearity, lower limit of quantification (LOQ), lower limit of detection (LOD), accuracy, precision, robustness and specificity were investigated. The proposed method showed linearity over the concentration range of (0.5-25 µg/mL) and (0.1-25 µg/mL) for FLU and AZL, respectively. Besides that, the method was adopted in a short chromatographic run with satisfactory resolution factors of (2.39, 3.78 and 6.74 between PEA/FLU, FLU/AZL and AZL/BNZ), respectively. The performed method was efficiently applied to pharmaceutical nasal spray with (mean recoveries ± SD) (99.80 ± 0.97) and (100.26 ± 0.96) for FLU and AZL, respectively. Conclusion: The suggested method was based on simultaneous determination of FLU and AZL in the presence of PEA and BNZ in pure form, laboratory synthetic mixture and its combined pharmaceutical dosage form using green MELC technique with UV detection. The proposed method appeared to be superior to the reported ones of being more sensitive and specific, as well as the separation was achieved with good performance in a relatively short analysis time (less than 7.5 min). Highly acceptable values of LOD and % RSD make this method superior to be used in quality control laboratories with of HPLC technique.

scholarly journals Electrochemical Detection of Endosulfan Using an AONP-PANI-SWCNT Modified Glassy Carbon Electrode

Materials ◽  
2021 ◽  
Vol 14 (4) ◽  
pp. 723
Author(s):  
Kgotla K. Masibi ◽  
Omolola E. Fayemi ◽  
Abolanle S. Adekunle ◽  
Amal M. Al-Mohaimeed ◽  
Asmaa M. Fahim ◽  
...  
Keyword(s):  
Glassy Carbon Electrode ◽  
Glassy Carbon ◽  
Limit Of Detection ◽  
Modified Electrodes ◽  
Antimony Oxide ◽  
Current Response ◽  
Carbon Electrode ◽  
Trace Detection ◽  
Limit Of Quantification ◽  
Walled Carbon Nanotubes

This report narrates the successful application of a fabricated novel sensor for the trace detection of endosulfan (EDS). The sensor was made by modifying a glassy-carbon electrode (GCE) with polyaniline (PANI), chemically synthesized antimony oxide nanoparticles (AONPs), acid-functionalized, single-walled carbon nanotubes (fSWCNTs), and finally, the AONP-PANI-SWCNT nanocomposite. The electrochemical properties of the modified electrodes regarding endosulfan detection were investigated via cyclic voltammetry (CV) and square-wave voltammetry. The current response of the electrodes to EDS followed the trend GCE-AONP-PANI-SWCNT (−510 µA) > GCE-PANI (−59 µA) > GCE-AONPs (−11.4 µA) > GCE (−5.52 µA) > GCE-fSWCNTs (−0.168 µA). The obtained results indicated that the current response obtained at the AONP-PANI-SWCNT/GCE was higher with relatively low overpotential compared to those from the other electrodes investigated. This demonstrated the superiority of the AONP-PANI-SWCNT-modified GCE. The AONP-PANI-SWCNT/GCE demonstrated good electrocatalytic activities for the electrochemical reduction of EDS. The results obtained in this study are comparable with those in other reports. The sensitivity, limit of detection (LoD), and limit of quantification (LoQ) of AONP-PANI-SWCNT/GCE towards EDS was estimated to be 0.0623 µA/µM, 6.8 µM, and 20.6 µM, respectively. Selectivity, as well as the practical application of the fabricated sensor, were explored, and the results indicated that the EDS-reduction current was reduced by only 2.0% when interfering species were present, whilst average recoveries of EDS in real samples were above 97%.

scholarly journals SaQuant: a real-time PCR assay for quantitative assessment of Staphylococcus aureus

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Colin Wood ◽  
Jason Sahl ◽  
Sara Maltinsky ◽  
Briana Coyne ◽  
Benjamin Russakoff ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Sensitivity And Specificity ◽  
Pathogen Detection ◽  
Limit Of Detection ◽  
Future Research ◽  
Limit Of Quantification ◽  
Pathogen Prevalence ◽  
Single Well ◽  
Effective Public Health ◽  
Detection And Quantification

Abstract Background Molecular assays are important tools for pathogen detection but need to be periodically re-evaluated with the discovery of additional genetic diversity that may cause assays to exclude target taxa or include non-target taxa. A single well-developed assay can find broad application across research, clinical, and industrial settings. Pathogen prevalence within a population is estimated using such assays and accurate results are critical for formulating effective public health policies and guiding future research. A variety of assays for the detection of Staphylococcus aureus are currently available. The utility of commercial assays for research is limited, given proprietary signatures and lack of transparent validation. Results In silico testing of existing peer-reviewed assays show that most suffer from a lack of sensitivity and specificity. We found no assays that were specifically designed and validated for quantitative use. Here we present a qPCR assay, SaQuant, for the detection and quantification of S. aureus as might be collected on sampling swabs. Sensitivity and specificity of the assay was 95.6 and 99.9 %, respectively, with a limit of detection of between 3 and 5 genome equivalents and a limit of quantification of 8.27 genome equivalents. The presence of DNA from non-target species likely to be found in a swab sample, did not impact qualitative or quantitative abilities of the assay. Conclusions This assay has the potential to serve as a valuable tool for the accurate detection and quantification of S. aureus collected from human body sites in order to better understand the dynamics of prevalence and transmission in community settings.

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