bluuebunny/crossref_metadata_2025_split huggingface dataset:
Laboratory Utilization and Analytical Validation of Fecal Electrolyte Tests
Authors: Parakh Rugvedita , Greene Dina N , Mathias Patrick C , Block Darci R , Ranjitkar Pratistha 
Published: July 2018

Abstract

Background
Chronic diarrhea can be categorized as fatty, watery, or inflammatory. Watery diarrhea is further divided into secretory or osmotic types and can be differentiated by measuring fecal electrolytes and osmotic gap. However, with widespread use of endoscopy, it is unclear if these measurements are being used clinically. Furthermore, because stool is not a validated specimen type for Food and Drug Administration–approved electrolyte assays, utilization is a practical concern for laboratories before analytical validation. Here, we determined the clinical utility and validated the performance characteristics of stool electrolytes on the Beckman Coulter AU680.

Methods
Historical results and literature review were used to determine the clinically relevant ranges for stool electrolytes (Na+, Cl−, K+, phosphate, and Mg2+). Additionally, medical chart review was performed (n = 44 patients) on results to evaluate their clinical utility in chronic diarrhea work-up. Linearity, precision, and stability studies were performed on the AU680. Accuracy was evaluated by comparing results to the Roche Cobas 6000 c501.

Results
For all cases, stool electrolytes and osmotic gap proved valuable in chronic diarrhea work-up. The imprecision of the assays ranged from 0% to 5.9%. All assays were found to be linear within the instrument's analytical measurement range with appropriate slopes and intercepts. The bias between the AU680 and the Roche c501 ranged from −0.48 to 2.39 (mmol/L or mg/dL). Na+, Cl−, and K+ were stable refrigerated for 5 days and up to 1 freeze-thaw cycle. Phosphate and Mg2+ were stable refrigerated for 48 h, but unstable to freeze-thaw cycles.

Conclusions
Stool osmotic gap is valuable for evaluating chronic diarrhea and can be calculated using electrolyte concentrations measured on the AU680.
Application of a Simulation Model to Estimate Treatment Error and Clinical Risk Derived from Point-of-Care International Normalized Ratio Device Analytic Performance
Authors: Lyon Martha E , Sinha Roona , Lyon Oliver A S , Lyon Andrew W 
Published: July 2018

Abstract

Background
In 2016, the Food and Drug Administration (FDA) proposed to enhance performance expectations for point-of-care testing (POCT) international normalized ratio (INR) devices relative to International Organization for Standardization (ISO) 17593:2007. The objective of the study was to estimate the frequency of warfarin dosing errors associated with a central laboratory INR method, a POCT INR method, and the proposed FDA performance goals.

Methods
A data set of INR results (n = 51912) from adult patients with INR ≤4 was used to assess the influence of adding assay imprecision and bias on warfarin dose decisions. The frequency of error in warfarin dose and size of error (≥1 or ≥2 dose categories) was compared using published assay specifications for the Instrumentation Laboratory ACL TOP® and the Roche Diagnostics CoaguChek® XS relative to the proposed FDA guidelines.

Results
The frequency of warfarin dose misclassification was largely influenced by bias and was not sensitive to assay imprecision. The central laboratory and POCT INR methods met the FDA performance specifications, had equal rates of ≥2 warfarin dose category error, and had statistically different rates of ≥1 warfarin dose category error in large samples (n &gt;250).

Conclusions
Simulation models are useful tools for evaluating POCT INR assay performance criteria required to achieve the proposed FDA guidelines. This simulation depicted how the Roche Diagnostics CoaguChek XS instrument meets the guideline.
Use of Automation and Process Improvement to Achieve a Six Sigma Level of Nonanalytic Quality
Authors: Messinger Bonnie L , Rogers David N , Hawker Charles D 
Published: July 2018

Abstract

Background
Clinical laboratories have focused on quality for more than 60 years. While analytic quality is considered excellent in most laboratories, nonanalytic quality is an area for focused improvement. One of our quality metrics, lost samples, has been tracked continuously for 25 years and has demonstrated steady improvement. Nonanalytic processes have become highly automated within our organization, which, we believe, was a major factor in reducing lost samples. We have also implemented numerous behavioral controls and completed many process reengineering projects that have had a demonstrable effect on lost sample rates. Our objective in this study was to determine the overall contributions of our error-proofing methods to reducing lost samples.

Methods
Using data spanning 25 years, we plotted the correlation between lost samples and the implementation dates for 8 major phases of automation along with 16 process improvements and engineering controls.

Results
The lost sample rate decreased nearly 100-fold. In Six Sigma terms, the 12-month moving average for lost samples currently hovers around 5.85-sigma, with several months at or better than 6-sigma. While implementation of process improvements, engineering controls, and automation all contributed to the reduction, automation was the most significant contributor.

Conclusions
The custom automation in use by our laboratory has led to improved nonanalytic quality. Although this level of automation might not be possible for all laboratories, our description of 16 behavior and engineering controls may be useful to other laboratories seeking to design high-quality nonanalytic processes.
Effects of Plasma Exchange and Heparin Concentration on the Serotonin Release Assay in Heparin-Induced Thrombocytopenia
Authors: Tillman Benjamin F , Matafonov Anton , Kingeter Adam J , Shah Ashish S , Gailani David 
Published: July 2018

Abstract

Background
Heparin-induced thrombocytopenia (HIT) is a hypercoagulable state caused by a transient antibody to heparin-bound platelet factor 4 (PF4). Treatment involves discontinuing heparin and administering a nonheparin anticoagulant. Procedures requiring heparin, such as cardiopulmonary bypass, are preferably delayed until the offending antibody is no longer detectable. For patients with a high-titer anti-PF4-heparin antibody and who require exposure to heparin, therapeutic plasma exchange (TPE) has been used to remove the antibody. Recent work indicates that a functional assay for detecting platelet-activating antibodies in HIT patients, the serotonin release assay (SRA), is preferable to ELISAs for anti-PF4-heparin antibodies for following the effectiveness of plasma exchange.

Methods
Two cases of acute heparin-induced thrombocytopenia managed with plasma exchange before emergent cardiac surgery were evaluated with SRAs using a range of heparin concentrations that included those used in cardiopulmonary bypass.

Results
We observed that a single round of plasma exchange led to greater reduction in platelet reactivity at heparin concentrations between 1 and 3 U/mL than at lower concentrations, consistent with the impression that heparin-PF4-antibody complexes form optimally within a limited heparin concentration range.

Conclusions
The findings suggest there may be a range of heparin concentration in which cardiac surgery may be safely performed in HIT patients, and that a single TPE in an emergent setting may lower antibody concentration sufficiently to lower platelet reactivity in the presence of heparin.
Pervasive Gabapentin Interference in the LC-MS/MS Analysis of Amphetamine
Authors: Shugarts Sarah B 
Published: July 2018

Abstract

Background
An LC-MS/MS urine confirmation assay was developed using a “dilute and shoot” sample preparation method that was subject to interference arising from gabapentin column overload in approximately 4% of patient samples, leading to interference in amphetamine analysis.

Methods
The initial analysis method used dilute and shoot sample preparation followed by LC-MS/MS analysis. The improved assay used solid-phase extraction sample preparation followed by LC-MS/MS analysis.

Results
The improved assay using solid-phase extraction and alternative chromatographic conditions resolved the gabapentin interference in amphetamine analysis.

Conclusions
This experience illustrates the importance of thorough knowledge of likely comedications in a patient population and these drugs' elimination mechanisms. Laboratorians should be aware of the phenomenon of mass effect LC-MS/MS interference, in addition to the more common LC-MS/MS interferences caused by matrix effects and isobaric compounds.
Analytical Considerations When Developing an LC-MS/MS Method for More than 30 Analytes
Authors: Enders Jeffrey R , Smith Jeremy P , Feng Sheng , Strickland Erin C , McIntire Gregory L 
Published: July 2018

Abstract

Background
While validation of analytical (LC-MS/MS) methods has been documented in any number of articles and reference texts, the optimal design and subsequent validation of a method for over 30 analytes presents special challenges. Conventional approaches to calibration curves, controls, and run time are not tenable in such methods. This report details the practical aspects of designing and implementing such a method in accordance with College of American Pathologists validation criteria.

Methods
Conventional criteria were followed in the design and validation of a method for 34 analytes and 15 internal standards by LC-MS/MS. These criteria are laid out in a standard operating procedure, which is followed without exception and is consistent with College of American Pathologists criteria.

Results
The method presented herein provides quality results and accurate medication monitoring. The method was optimized to negate interferences (both from within the method and from potential concomitant compounds), increase throughput, and provide reproducible quality quantification over relevant analyte concentrations ranges.

Conclusions
The method was designed primarily with quality and accurate medication monitoring in mind. The method achieves these goals by use of novel approaches to calibration curves and controls that both improve performance and minimize risk (financial and operational). As automation and LC-MS/MS equipment continue to improve, it is expected that more methods like this one will be developed.
Selective, Accurate, and Precise Quantitation of Glutarylcarnitine in Human Urine from a Patient with Glutaric Acidemia Type I
Authors: Minkler Paul E , Stoll Maria S K , Ingalls Stephen T , Hoppel Charles L 
Published: July 2018

Abstract

Background
Although correctly used in expanded newborn screening programs to identify patients with possible diseases, flow-injection tandem mass spectrometry (MS/MS) acylcarnitine “profiles” are inadequate for standard clinical uses owing to their limited quantitative accuracy and lack of selectivity. We report the application of our selective, accurate, and precise method for quantification of acylcarnitines, applied to urine glutarylcarnitine from a patient with glutaric acidemia type I (GAI).

Methods
A previously validated acylcarnitine ultra-HPLC-MS/MS method was used, with a focus on analysis of glutarylcarnitine. Calibrants and samples were isolated by solid-phase extraction and derivatized with pentafluorophenacyl trifluoromethanesulfonate. Acylcarnitine pentafluorophenacyl esters were eluted in 14-min chromatograms. Standardized calibrants and a 13-point, 200-fold concentration range calibration curve were used for accurate quantification of glutarylcarnitine. Quality control samples validated method accuracy and long-term analytic stability.

Results
Quantification of glutarylcarnitine in urine from a patient with GAI is reported. Long-term analytical stability of the method over a 5-year period is shown.

Conclusions
Our method for acylcarnitine quantification is shown to be selective, accurate, and precise; thus, we recommend it for confirmatory testing and monitoring of plasma and urine samples from patients with GAI.
Development and Population Results of a Fully Automated Homogeneous Assay for LDL Triglyceride
Authors: Ito Yasuki , Ohta Motoko , Ikezaki Hiroaki , Hirao Yuhko , Machida Asako , Schaefer Ernst J , Furusyo Norihiro 
Published: July 2018

Abstract

Background
Low-density lipoprotein (LDL) is measured by its cholesterol content (LDL-C), but it has been suggested that LDL triglyceride (LDL-TG) may also be related to coronary artery disease risk. LDL-TG can be measured after ultracentrifugation or electrophoresis, but these are labor intensive methods, indicating the need for an automated homogeneous assay.

Methods
TG-rich lipoproteins (TRLs), LDL, and HDL were isolated by ultracentrifugation and used to determine optimal characteristics of surfactants and various enzymes for assay development. We analyzed assay precision and linearity, and compared results with those obtained after ultracentrifugation. Serum samples from a large population study (n = 12284 subjects) were used to generate reference intervals for LDL-TG and to determine levels in various types of hyperlipidemia.

Results
An assay for LDL-TG has been developed by use of surfactants 1 and 2, and enzymes to measure LDL-TG directly on an automated analyzer. There was an excellent correlation between results obtained with this assay and after isolation of LDL by ultracentrifugation. When the assay was applied to serum samples from normal and hyperlipidemic subjects, median normal values were 0.09 mmol/L, with significant median elevations observed in subjects with increased LDL-C, hypertriglyceridemia, combined hyperlipidemia, and hyperchylomicronemia of 0.19, 0.18, 0.28, and 0.43 mmol/L, respectively, as compared with mean LDL-C values in these subjects of 2.25, 4.01, 2.66, 3.96, and 2.43 mmol/L, respectively.

Conclusions
We have developed an automated homogeneous assay for LDL-TG for potential use in research and clinical laboratories, and documented that the TG molar content of LDL is about 5% of its cholesterol content.
Thrombophilia: Women-Specific Reference Ranges Can Prevent Misdiagnosis in Women
Authors: Veen Caroline S B , Durian Marc F , Kruip Marieke J.H.A , Ahmadi Mustafa , Petronia Sizwe M , van Asten Sjef G , Visser Willy , de Maat Moniek P M 
Published: July 2018

Abstract

Background
Thrombophilia is a state where abnormalities of the hemostatic system predispose a patient to thrombosis. Some coagulation factors are generally lower in women than in men. Therefore, the use of routine reference ranges (RRRs) based on male or mixed-sex groups may be misleading in the diagnosis of thrombophilia in women. We hypothesize that this affects the analysis of thrombophilia after pregnancy complications. Therefore, the aim of our study was to investigate the effect of women-specific reference ranges (WRRs) on the interpretation of hemostatic variables in postpartum women.

Methods
Coagulant and anticoagulant variables were measured 3 months postpartum in 61 healthy women with an uncomplicated pregnancy and in 197 women who experienced preeclampsia (PE). In 55 of the healthy women, these variables were also measured at least 6 months after an uncomplicated pregnancy and used to calculate WRR.

Results
In total, 48% of healthy women had normal results when using routine reference ranges compared with 89% when using WRRs (P &lt; 0.05). In the women with PE, there were normal results in 26% of women when using routine reference ranges compared with 66% when using WRRs (P &lt; 0.05).

Conclusion
When using WRRs, fewer abnormalities were seen in healthy women as well as in women with a history of PE, which may prevent misdiagnosis of thrombophilia.
Method Performance of Bicarbonate and Electrolytes by Use of Duodenal Fluid for Assessment of Exocrine Pancreatic Function
Authors: Pyle-Eilola Amy , Pagan Jill , Kayatin Adam , Povse Patrick N , Rietschlin Jacqua A , Cotten Steven W 
Published: July 2018

Abstract

Background
Evaluation of exocrine pancreatic insufficiency is challenging for both clinicians and laboratories. Indirect pancreatic function tests such as serum trypsinogen, fecal elastase, and fecal fat measurements are moderately sensitive for diagnosis of advanced chronic pancreatitis but show reduced sensitivity and specificity for diagnosis of early disease. An alternative is the endoscopic pancreatic function test, which uses duodenal secretions after administration of IV secretin. Samples are collected at various times via the endoscopic tube and then analyzed for bicarbonate, sodium, potassium, and chloride.

Methods
Precision, linearity, method comparison, and stability studies were performed on the Beckman Coulter AU5822 chemistry analyzer with duodenal fluid. Comparison with the Vitros 4600 dry slide chemistry instrument was used to interrogate differences between methods.

Results
All assays produced a CV &lt;2% without any measurable effects from the endoscopy fluid matrix and showed acceptable imprecision near the limit of detection (CV &lt; 5%). All analytes showed linear dilution across the analytical measuring range. All the calculated error biases from dilutions were within 50% of the CLIA-allowable error for serum for each of the respective analytes. The calculated slopes ranged from 0.841 to 1.274 when compared to the Vitros 4600. Stability studies demonstrated that sodium, potassium, chloride, and bicarbonate remained stable after storage at −20 °C and after multiple freeze–thaw cycles. The percent change for all analytes was &lt;5% mmol/L.

Conclusions
The AU5800 series demonstrated adequate performance for the analysis of bicarbonate in duodenal fluid and therefore can be used for assessment of exocrine pancreatic function. However, notable discrepancies were observed for sodium, potassium, and chloride between the AU5800 series and the Vitros 4600.
A Novel Approach to Estimating M-Protein Concentration: Capillary Electrophoresis Quantitative Immunosubtraction
Authors: Schroeder Lee F , Huls Forest , Williams Christopher L , Li Shih-Hon , Keren David F 
Published: July 2018

Abstract

Introduction
M-protein quantification is routinely performed by demarcating serum protein electrophoresis (SPE) regions. However, quantification of β-migrating M-protein is hindered by overlapping nonimmunoglobulin protein. Immunosubtraction (ISUB) on capillary electrophoresis is a method currently used qualitatively to subtract out (and therefore highlight) immunoglobulin isotypes in serum, thus reducing the masking effect of normal serum proteins. This study expands on traditional ISUB by developing a quantitative immunosubtraction (qIS) methodology.

Methods
qIS is achieved by estimating the monoclonal class-specific immunoglobulin contribution to the SPE region containing the M-protein. We conducted a recovery study by use of serial dilutions from 3 patients with β-region M-proteins (n = 22), performing SPE and ISUB on each dilution. We visualized the difference between the ISUB electrophoresis trace and the involved ISUB isotype-subtracted trace to distinguish M-protein and background polyclonal immunoglobulins, which was demarcated independently by 3 pathologists. The M-protein contribution to the β-region was calculated and applied to the β-region protein concentration producing the quantitative M-protein concentration, while minimizing contamination by nonimmunoglobulin or polyclonal immunoglobulin proteins.

Results
Using a quality target of 25% error, we determined that our analytical measurable range spanned the maximum concentration tested (0.81 g/dL) to 0.05 g/dL. Passing–Bablok regression between qIS and the expected M-protein produced a slope of 1.04 (95% CI, 0.94–1.09), r = 0.99. Total CV was 4.8% and intraclass correlation between pathologists was 0.998.

Discussion
qIS promises quantification of β-migrating M-proteins at concentrations an order of magnitude lower than traditional SPE methodology, allowing earlier detection of increasing or decreasing M-protein.
A Stubborn Case of Syphilitic Hepatitis
Authors: Campitelli Marco , Al Moussawi Hassan , Zeineddine Nabil , Maslak Stephen 
Published: July 2018

Background
Syphilitic hepatitis is a rare occurrence, but delay in its diagnosis can expose patient to unnecessary testing. The treatment available for this condition can also vary from one intramuscular injection of Penicillin G to a 2-weeks course of intravenous penicillin.
Case presentation:
A 53 years old male, presented for fever and abdominal pain, was found on physical examination to have a macular rash on the palms and soles, with fever and abdominal tenderness.
Laboratory findings revealed AST 199 IU/L, ALT 132 IU/L, positive RPR, FTA-ABS and HIV antibodies test and a high HIV viral load.
He was diagnosed with secondary syphilis and HIV co-infection. His hepatitis did not improve after intramuscular injection of penicillin G, his symptoms continued to worsen. A liver biopsy was done and revealed acute hepatitis and canalicular cholestasis, without evidence of treponemes.
Patient was started on intravenous penicillin. He showed significant clinical improvement, and his LFT normalized.
Conclusion:
This case describes severe syphilitic hepatitis with unusual cytolytic disturbance of the liver function that failed to improve with one intramuscular penicillin injection. It demonstrates the need of intravenous penicillin therapy to achieve adequate clinical response, particularly in patients with severe laboratory evidence of liver inflammation.
To Study The Serum Vitamin –D And Oxidative Stress Status In Rheumatoid Arthritis
Authors: Uma T 
Published: July 2018

Aim and objectives: Rheumatoid arthritis (RA) is a chronic autoimmune systemic disease characterized predominantly by synovial inflammation, leading to joint destruction. The study was undertaken to analyze the vitamin –D and oxidative stress status in Rheumatoid arthritis

Materials and methods: The Study includes Patients diagnosed as RA by using RA factor within the age group of30 to 60 years and comprised of 20 age matched control group. To assess oxidative stress, serum Malonyldialdehyde (MDA) was by thiobarbituric acid method and antioxidant level was assessed by estimation of serum vitamin C by dinitrophenyl hydrazine method. And vitamin D total is estimated by chemiluminescent immunoassay.
Results: There is a significant decreased level of vitamin -D in the RA patients (37.58±5.7ng/ml) as compared to healthy controls (58.5±5.6ngl/ml). There is a a significant increased levels of MDA in the RA patients (7.6±1.09) as compared to healthy controls (8.4±2.8). There is a significant decreased level of vitamin -c in the RA patients (0.6±0.3mg/dl) as compared to healthy controls (1.0±0.31mg/dl).

Conclusion: Low levels of Vitamin D deficiency in RA patients is associated with inflammation which leads to Increased oxidative stress status , which may lead to connective tissue degradation leading to joint and periarticular deformities in rheumatoid arthritis.
“Public Health Hints: How To Best Breath And More Which Everyone Must Know And Use To Be Healthy!”--
Authors: Nigro Samuel A. 
Published: July 2018

Simple clinical health improving procedures are offered which should be promoted by public health organizations everywhere. These procedures are the result of discovering the cure for the author's severe laryngospasm disorder. Discovering the SAM prompted reflections on improving simple valuable self-care for all. All techniques are described and recommended for improving health care and comfortable living for everyone everywhere old enough to follow directions. They have to be daily practiced and made routine.