[Show abstract][Hide abstract] ABSTRACT: The measurement of free immunoglobulin light chains is typically performed on serum; however, the use of alternative specimen types has potential benefits. Using the Freelite™ kappa and lambda free light chains assay on a Roche Diagnostics cobas 8000 c502 analyzer, we compared three specimen types (serum, EDTA-plasma and lithium heparin plasma separator gel-plasma) on 100 patients. Using Deming regression and eliminating outliers (limiting data to light chain concentrations below 400 mg/L), the three specimen types showed comparable results for kappa light chain concentration, lambda light chain concentration, and kappa/lambda ratio with slopes close to 1.0 and y-intercepts close to zero. EDTA-plasma showed slightly more positive bias relative to serum than lithium heparin. Analysis using EDTA-plasma and lithium heparin plasma showed comparable linearity, precision, and temperature stability. A single sample showing hook effect (not in the comparison set) gave comparable results using either plasma specimen type. For the Freelite™ kappa and lambda free light chains assay, both EDTA-plasma or lithium heparin-plasma can serve as acceptable substitutes for serum, at least for the Roche cobas 8000 analyzer.
[Show abstract][Hide abstract] ABSTRACT: This case study over time describes five years of experience with interventions to improve laboratory test utilization at an academic medical center. The high-frequency laboratory tests showing the biggest declines in order volume post intervention were serum albumin (36%) and erythrocyte sedimentation rate (17%). Introduction of restrictions for 170 high-cost send-out tests resulted in a 23% decline in order volume. Targeted interventions reduced mis-orders involving several “look-alike” tests: 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D; manganese, magnesium; beta-2-glycoprotein, beta-2-microglobulin. Lastly, targeted alerts reduced duplicate orders of germline genetic testing and orders of hepatitis B surface antigen within 2 weeks of hepatitis B vaccination.
Electronic supplementary material
The online version of this article (doi:10.1186/s12911-015-0137-7) contains supplementary material, which is available to authorized users.
Full-text · Article · Dec 2015 · BMC Medical Informatics and Decision Making
[Show abstract][Hide abstract] ABSTRACT: Ethylene glycol (EG) is a common cause of toxic ingestions. Gas chromatography (GC)-based laboratory assays are the gold standard for diagnosing EG intoxication. However, GC requires specialized instrumentation and technical expertise that limits feasibility for many clinical laboratories. The objective of this retrospective study was to determine the utility of incorporating a rapid EG assay for management of cases with suspected EG poisoning. The University of Iowa Hospitals and Clinics core clinical laboratory adapted a veterinary EG assay (Catachem, Inc.) for the Roche Diagnostics cobas 8000 c502 analyzer and incorporated this assay in an osmolal gap-based algorithm for potential toxic alcohol/glycol ingestions. The main limitation is that high concentrations of propylene glycol (PG), while readily identifiable by reaction rate kinetics, can interfere with EG measurement. The clinical laboratory had the ability to perform GC for EG and PG, if needed. A total of 222 rapid EG and 24 EG/PG GC analyses were documented in 106 patient encounters. Of ten confirmed EG ingestions, eight cases were managed entirely with the rapid EG assay. PG interference was evident in 25 samples, leading to 8 GC analyses to rule out the presence of EG. Chart review of cases with negative rapid EG assay results showed no evidence of false negatives. The results of this study highlight the use of incorporating a rapid EG assay for the diagnosis and management of suspected EG toxicity by decreasing the reliance on GC. Future improvements would involve rapid EG assays that completely avoid interference by PG.
No preview · Article · Nov 2015 · Journal of medical toxicology: official journal of the American College of Medical Toxicology
[Show abstract][Hide abstract] ABSTRACT: Objectives:
The primary objective of this study was to evaluate potential interference of Trinder-based chemistry assays by N-acetylcysteine (NAC). A secondary objective was to look for evidence of interference in patients treated with NAC for acetaminophen (APAP) overdose.
Design and methods:
Dilutions of NAC in plasma were tested for interference using the following Roche Diagnostics Trinder-based assays on a cobas 8000 system: enzymatic creatinine (Cr), cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), triglycerides (TRIG), and uric acid (UA). Two non-Trinder Roche assays - urea nitrogen (BUN) and glucose (GLUC) - were tested as controls. Sekisui N-geneous® low-density lipoprotein cholesterol (LDL-C) reagent was also evaluated. Retrospective chart review of APAP overdose cases over 49months was conducted to look for differences in plasma Cr before and after intravenous (IV) NAC administration.
NAC concentrations (shown in parentheses) that caused ≥10% inhibition for individual assays were (in order of sensitivity to interference): TRIG (570mg/L)>CHOL (740mg/L)≈Cr (790mg/L)>UA (1100mg/L)>HDL-C (1760mg/L)>LDL-C (2900mg/L). Neither BUN nor GLUC achieved significant inhibition up to 10,000mg/L NAC. Evidence for relatively minor inhibition of Cr was observed in patients after NAC administration.
NAC inhibition of the assays investigated typically occurs at concentrations higher than expected during IV and oral NAC therapy.
No preview · Article · Oct 2015 · Clinical biochemistry
[Show abstract][Hide abstract] ABSTRACT: Pathology data contained within the electronic health record (EHR), and laboratory information system (LIS) of hospitals represents a potentially powerful resource to improve clinical care. However, existing reporting tools within commercial EHR and LIS software may not be able to efficiently and rapidly mine data for quality improvement and research applications.
We present experience using a data warehouse produced collaboratively between an academic medical center and a private company. The data warehouse contains data from the EHR, LIS, admission/discharge/transfer system, and billing records and can be accessed using a self-service data access tool known as Starmaker. The Starmaker software allows users to use complex Boolean logic, include and exclude rules, unit conversion and reference scaling, and value aggregation using a straightforward visual interface. More complex queries can be achieved by users with experience with Structured Query Language. Queries can use biomedical ontologies such as Logical Observation Identifiers Names and Codes and Systematized Nomenclature of Medicine.
We present examples of successful searches using Starmaker, falling mostly in the realm of microbiology and clinical chemistry/toxicology. The searches were ones that were either very difficult or basically infeasible using reporting tools within the EHR and LIS used in the medical center. One of the main strengths of Starmaker searches is rapid results, with typical searches covering 5 years taking only 1-2 min. A "Run Count" feature quickly outputs the number of cases meeting criteria, allowing for refinement of searches before downloading patient-identifiable data. The Starmaker tool is available to pathology residents and fellows, with some using this tool for quality improvement and scholarly projects.
A data warehouse has significant potential for improving utilization of clinical pathology testing. Software that can access data warehouse using a straightforward visual interface can be incorporated into pathology training programs.
[Show abstract][Hide abstract] ABSTRACT: Serum angiotensin converting enzyme (ACE) levels may be decreased by use of ACE inhibitor (ACEI) medication. In this study, we determined how often ACE levels were performed in patients receiving ACEI therapy.
ACE levels analyzed over a 54 month "pre-intervention" time period at an academic medical center were reviewed retrospectively for tests performed during ACEI therapy. This data was compared with a large, de-identified dataset of ACE levels performed at a national reference laboratory, in vitro studies of ACEI inhibition, and liquid chromatography-time-of-flight mass spectrometry (LC-TOF-MS) detection of lisinopril in a subset of clinical specimens.
Over a 54 month period, 1,292 patients had ACE levels performed, with 108 patients (8.4%) on ACEI therapy at time of testing. ACE levels performed for patients on ACEI therapy were substantially lower. In general, clinical teams did not recognize medication effect on ACE levels. Introduction of a warning prompt in the electronic health record reduced ordering of ACE levels in patients on ACEIs by more than 60% in a seventeen month "post-intervention" time period. The de-identified dataset of ACE levels at a reference laboratory showed a bimodal distribution, with a peak of very low ACE levels. Using LC-TOF-MS, the presence of lisinopril was confirmed in a subset of specimens with low ACE activity. In vitro studies of two different ACE assays showed significant inhibition of activity at clinically relevant concentrations.
Assessment of ACE activity is often performed for patients on ACEIs, potentially leading to low ACE concentrations and inaccurate interpretations.
[Show abstract][Hide abstract] ABSTRACT: Thyroglobulin (Tg) is used as a tumor marker to monitor disease progression and recurrence of differentiated thyroid cancers. However, Tg measured by standard immunoassay (IMA) is not a reliable marker in the presence of anti-Tg antibodies (TgAbs) due to interference that may result in either false positive or false negative results. TgAbs concentrations are used to monitor for cancer recurrence thus making DTC in these cases more challenging. The levels of TgAbs can be high not only due to recurrence of thyroid cancer but also due to exogenous administration of immunoglobulins (Ig).
We present an example of elevated Tg Abs due to administration of subcutaneous immunoglobulin (SCIg) in a patient with thyroid cancer.
A 57 year old man was diagnosed with stage I papillary thyroid cancer (PTC). Tg Abs were negative prior to the diagnosis of thyroid cancer and became positive after thyroidectomy and radioactive iodine. A detailed work-up including whole body scan did not reveal recurrent disease. He had been diagnosed with CVID and dermatomyositis at the age of 50 and was started on immunoglobulin replacement therapy shortly after diagnosis. Tg was negative when assessed with a liquid chromatography-mass spectrometry assay (LC-MS/MS). Therefore, elevated Tg Ab titers were attributed to concomitant treatment with SCIg. We also demonstrated SCIg medication had Tg Ab activity that was removed by protein A column treatment. Dilutions of SCIg medication also caused positive IgG serologies for cytomegalovirus, herpes simplex, measles, mumps, rubella, and varicella-zoster viruses.
Exogenous source of TgAbs from SCIg lead to extensive imaging work-up to assess for recurrence of PTC. LC-MS/MS is a conceptually attractive approach to overcome TgAb interference with Tg IMA measurement.
No preview · Article · Jul 2015 · Endocrine Practice
[Show abstract][Hide abstract] ABSTRACT: Clinical laboratories frequently receive orders to perform additional tests on existing specimens ('add-ons'). Previous studies have examined add-on ordering patterns over short periods of time. The objective of this study was to analyze add-on ordering patterns over an extended time period. We also analyzed the impact of a robotic specimen archival/retrieval system on add-on testing procedure and manual effort.
In this retrospective study at an academic medical center, electronic health records from were searched to obtain all add-on orders that were placed in the time period of May 2, 2009 to December 31, 2014.
During the time period of retrospective study, 880,359 add-on tests were ordered on 96,244 different patients. Add-on testing comprised 3.3 % of total test volumes. There were 443,411 unique ordering instances, leading to an average of 1.99 add-on tests per instance. Some patients had multiple episodes of add-on test orders at different points in time, leading to an average of 9.15 add-on tests per patient. The majority of add-on orders were for chemistry tests (78.8 % of total add-ons) with the next most frequent being hematology and coagulation tests (11.2 % of total add-ons). Inpatient orders accounted for 66.8 % of total add-on orders, while the emergency department and outpatient clinics had 14.8 % and 18.4 % of total add-on orders, respectively. The majority of add-ons were placed within 8 hours (87.3 %) and nearly all by 24 hours (96.8 %). Nearly 100 % of add-on orders within the emergency department were placed within 8 hours. The introduction of a robotic specimen archival/retrieval unit saved an average of 2.75 minutes of laboratory staff manual time per unique add-on order. This translates to 24.1 hours/day less manual effort in dealing with add-on orders.
Our study reflects the previous literature in showing that add-on orders significantly impact the workload of the clinical laboratory. The majority of add-on orders are clinical chemistry tests, and most add-on orders occur within 24 hours of original specimen collection. Robotic specimen archival/retrieval units can reduce manual effort in the clinical laboratory associated with add-on orders.
Preview · Article · Jun 2015 · BMC Clinical Pathology
[Show abstract][Hide abstract] ABSTRACT: The case study is a 33-year-old white female with persistently elevated serum human chorionic gonadotropin (hCG) levels following methotrexate treatment and emergency surgery for ectopic pregnancy. At the time of the first methotrexate dose, the serum hCG concentration was 27,995 IU/L. The laboratory was consulted 3.5 months after the surgery, because serum hCG levels had stopped declining and had leveled off to around 80 to 90 IU/L but with negative urine pregnancy tests. Laboratory studies ruled out heterophile antibody interference and hook effect by multiple methods including analysis by different serum hCG assays, treatment with heterophile antibody blocking agents, and dilution studies. Three additional doses of methotrexate over six months were required for serum hCG concentrations to decline to undetectable levels. This case illustrates challenges that may arise with serum hCG measurements in management of ectopic pregnancies. Close collaboration between the laboratory and clinical service is key for optimal patient care.
No preview · Article · Jun 2015 · Laboratory Medicine
[Show abstract][Hide abstract] ABSTRACT: Background:
Pentobarbital is used for management of intractable seizures and for reducing elevated intracranial pressure. Dosing of pentobarbital can be aided by therapeutic drug monitoring (TDM). There is no commercially available automated assay for measurement of pentobarbital serum/plasma concentrations; consequently, chromatography-based assays are often used.
Pentobarbital TDM was studied over a 14-year period at an academic medical center. 154 patients (94 adult, 60 pediatric) were identified who had pentobarbital levels ordered at least once during a hospital encounter. Chart review included patient diagnosis, indication for pentobarbital therapy, recent or concomitant medication with other barbiturates, patient disposition, organ donation, pentobarbital dosing changes, and neurosurgical procedures. Pentobarbital serum/plasma concentrations were determined on an automated clinical chemistry platform with a laboratory-developed test adapted from a urine barbiturates immunoassay.
Chart review showed therapeutic use of pentobarbital generally consistent with previously published literature. The most common errors observed involved confusion in barbiturate names (eg, mix-up of pentobarbital and phenobarbital in test ordering or in provider notes) that seemed to have minimal impact on TDM effectiveness, with pentobarbital serum/plasma concentrations generally within target ranges. The laboratory-developed pentobarbital immunoassay showed cross-reactivity with phenobarbital and butalbital that was eliminated by alkaline and heat pretreatment. The immunoassay was linear to 20 mcg/mL and correlated closely with gas chromatography-mass spectrometry measurements at a reference laboratory.
Pentobarbital TDM can be performed by immunoassay on an automated clinical chemistry platform, providing an alternative to chromatography-based methods. Confusion in barbiturate names is common, especially pentobarbital and phenobarbital.
No preview · Article · Apr 2015 · Therapeutic Drug Monitoring
[Show abstract][Hide abstract] ABSTRACT: Meconium drug testing is performed to detect potentially harmful drug exposures in a newborn. Interpretation of meconium drug testing results can be complicated based on the patterns and proportional concentrations of the drug(s) and/or drug metabolite(s) detected.
The objective of this study was to analyze meconium drug testing patterns in a de-identified dataset from a national reference laboratory (n=76,631) and in a subset of the data, wherein specimens originated at a single academic medical center for which detailed chart review was possible (n=3,635). Meconium testing was performed using eleven immunoassay-based drug screens. Specimens that were positive for one or more drug screens were reflexed to corresponding confirmation tests performed by gas- or liquid-chromatography with mass spectrometric detection, targeted to identify and quantitate specific parent drug(s) and metabolite(s).
The positivity rate was highest for the cannabis metabolite 11-nor-9-carboxy-Δ-tetrahydrocannabinol (25.2%, n=18,643), followed by opiates/oxycodone (23.2%, n=17,778), amphetamine/methamphetamine (6.7%, n=5,134), cocaine metabolites (5.5%, n=4,205), methadone (5.3%, n=4,093), benzodiazepines (3.4%, n=2,603), barbiturates (1.1%, n=834), propoxyphene (1.0%, n=749), and phencyclidine (0.1%, n=44). Based on documented pharmacy history, drugs administered to either the mother or newborn during the birth hospitalization were detected in meconium, providing evidence that drugs can be incorporated into meconium rapidly. Drugs administered directly to the newborn after birth were recovered in meconium as both parent drug and metabolites, providing evidence of neonatal metabolism. Overall, patterns observed in meconium exhibited many similarities to those patterns commonly reported with urine drug testing.
Interpretation of meconium drug testing results requires comparison of results with clinical and analytical expectations, including maternal admissions to drug use, pharmacy history, recognized metabolic patterns for drugs of interest, cutoff concentrations, and other performance characteristics of the test. Concentrations of drug(s) and drug metabolites(s) may not reliably predict timing of drug use, extent of drug use, or frequency of drug exposures.
No preview · Article · Jan 2015 · Therapeutic Drug Monitoring
[Show abstract][Hide abstract] ABSTRACT: Background:
Interfacing of clinical laboratory instruments with the laboratory information system (LIS) via “middleware” software is increasingly common. Our clinical laboratory implemented capillary electrophoresis using a Sebia® Capillarys-2™ (Norcross, GA, USA) instrument for serum and urine protein electrophoresis. Using Data Innovations Instrument Manager, an interface was established with the LIS (Cerner) that allowed for bi-directional transmission of numeric data. However, the text of the interpretive pathology report was not properly transferred. To reduce manual effort and possibility for error in text data transfer, we developed scripts in AutoHotkey, a free, open-source macro-creation and automation software utility.
Materials and Methods:
Scripts were written to create macros that automated mouse and key strokes. The scripts retrieve the specimen accession number, capture user input text, and insert the text interpretation in the correct patient record in the desired format.
The scripts accurately and precisely transfer narrative interpretation into the LIS. Combined with bar-code reading by the electrophoresis instrument, the scripts transfer data efficiently to the correct patient record. In addition, the AutoHotKey script automated repetitive key strokes required for manual entry into the LIS, making protein electrophoresis sign-out easier to learn and faster to use by the pathology residents. Scripts allow for either preliminary verification by residents or final sign-out by the attending pathologist.
Using the open-source AutoHotKey software, we successfully improved the transfer of text data between capillary electrophoresis software and the LIS. The use of open-source software tools should not be overlooked as tools to improve interfacing of laboratory instruments.
[Show abstract][Hide abstract] ABSTRACT: The objective of this study was to identify high-yield screening risk factors for detecting maternal non-medical drug use during pregnancy.
A four year retrospective analysis was conducted at an academic medical center. Detailed chart review of both the newborn and mother’s medical record was performed on all cases for which one or more drug(s) or metabolite(s) were identified and confirmed in meconium or urine.
229 (9.2%) of 2,497 meconium samples out of 7,749 live births confirmed positive for one or more non-medical drugs. History of maternal non-medical drug and/or tobacco use in pregnancy was present in 90.8% of non-medical drug use cases. Addition of social risk factors and inadequate prenatal care increased the yield to 96.9%.
Use of focused screening criteria based on specific maternal and social risk factors may detect many prenatal non-medical drug exposures.
[Show abstract][Hide abstract] ABSTRACT: Background
Immunoassays are widely used in clinical laboratories for measurement of plasma/serum concentrations of steroid hormones such as cortisol and testosterone. Immunoassays can be performed on a variety of standard clinical chemistry analyzers, thus allowing even small clinical laboratories to do analysis on-site. One limitation of steroid hormone immunoassays is interference caused by compounds with structural similarity to the target steroid of the assay. Interfering molecules include structurally related endogenous compounds and their metabolites as well as drugs such as anabolic steroids and synthetic glucocorticoids.
Cross-reactivity of a structurally diverse set of compounds were determined for the Roche Diagnostics Elecsys assays for cortisol, dehydroepiandrosterone (DHEA) sulfate, estradiol, progesterone, and testosterone. These data were compared and contrasted to package insert data and published cross-reactivity studies for other marketed steroid hormone immunoassays. Cross-reactivity was computationally predicted using the technique of two-dimensional molecular similarity.
The Roche Elecsys Cortisol and Testosterone II assays showed a wider range of cross-reactivity than the DHEA sulfate, Estradiol II, and Progesterone II assays. 6-Methylprednisolone and prednisolone showed high cross-reactivity for the cortisol assay, with high likelihood of clinically significant effect for patients administered these drugs. In addition, 21-deoxycortisol likely produces clinically relevant cross-reactivity for cortisol in patients with 21-hydroxylase deficiency, while 11-deoxycortisol may produce clinically relevant cross-reactivity in 11β-hydroxylase deficiency or following metyrapone challenge. Several anabolic steroids may produce clinically significant false positives on the testosterone assay, although interpretation is limited by sparse pharmacokinetic data for some of these drugs. Norethindrone therapy may impact immunoassay measurement of testosterone in women. Using two-dimensional similarity calculations, all compounds with high cross-reactivity also showed a high degree of similarity to the target molecule of the immunoassay.
Compounds producing cross-reactivity in steroid hormone immunoassays generally have a high degree of structural similarity to the target hormone. Clinically significant interactions can occur with structurally similar drugs (e.g., prednisolone and cortisol immunoassays; methyltestosterone and testosterone immunoassays) or with endogenous compounds such as 21-deoxycortisol that can accumulate to very high concentrations in certain disease conditions. Simple similarity calculations can help triage compounds for future testing of assay cross-reactivity.
[Show abstract][Hide abstract] ABSTRACT: Little is published about newborn drug testing in multiple gestations. The objective of this study was to review the results of meconium drug screening in multiple births to compare drug(s) and/or drug metabolite(s) detected. A retrospective analysis was conducted using data from a national reference laboratory and an academic medical center. The data were de-identified for the reference laboratory dataset. For the academic center data, a detailed chart review of the newborn and mother's medical record was performed on cases for which one or more drug(s) and/or metabolites(s) were identified and confirmed in meconium. Meconium was analyzed for amphetamine, methamphetamine, barbiturates, benzodiazepines, cannabinoid metabolites, cocaine metabolites, methadone, opiates, oxycodone, phencyclidine and propoxyphene. One hundred and forty-two of 1,084 sets of twins and 2 of 20 sets of triplets had mismatched results. The incidence of mismatched results among the individual drug or drug classes tested was 0.9% (208 of 23,848 total results). For the panel of drug testing performed, mismatches were seen in 13% (142 of 1,084) sets of twins and 10% (2 of 20) sets of triplets. Barbiturates (33%), opiates (30%) and benzodiazepines (28%) were the most common mismatches in the national reference laboratory dataset. Benzodiazepines (89%) and opiates (51%) were most common in the academic medical center dataset with most explained by iatrogenic medications administered to one infant but not the other. Mismatches for cannabinoids most often occurred when tetrahydrocannabinol metabolites were present at a low concentration (near lower reporting limit) in one infant but not the other. Mismatched results of meconium drug testing in multiples not explainable by differences in prescribed medications are uncommon and most often occur when an analyte is barely above reporting cutoff in only one infant. Administration of iatrogenic medications to one infant but not the other(s) is another frequent cause of such mismatches.
Full-text · Article · Jun 2014 · Journal of analytical toxicology
[Show abstract][Hide abstract] ABSTRACT: In the past twenty-one years, 17 new antiepileptic drugs have been approved for use in the United States and/or Europe. These drugs are clobazam, ezogabine (retigabine), eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, pregabalin, rufinamide, stiripentol, tiagabine, topiramate, vigabatrin and zonisamide. Therapeutic drug monitoring is often used in the clinical dosing of the newer anti-epileptic drugs. The drugs with the best justifications for drug monitoring are lamotrigine, levetiracetam, oxcarbazepine, stiripentol, and zonisamide. Perampanel, stiripentol and tiagabine are strongly bound to serum proteins and are candidates for monitoring of the free drug fractions. Alternative specimens for therapeutic drug monitoring are saliva and dried blood spots. Therapeutic drug monitoring of the new antiepileptic drugs is discussed here for managing patients with epilepsy.
No preview · Article · Jun 2014 · Clinica Chimica Acta
[Show abstract][Hide abstract] ABSTRACT: Background
A challenge for drug of abuse testing is presented by ‘designer drugs’, compounds typically discovered by modifications of existing clinical drug classes such as amphetamines and cannabinoids. Drug of abuse screening immunoassays directed at amphetamine or methamphetamine only detect a small subset of designer amphetamine-like drugs, and those immunoassays designed for tetrahydrocannabinol metabolites generally do not cross-react with synthetic cannabinoids lacking the classic cannabinoid chemical backbone. This suggests complexity in understanding how to detect and identify whether a patient has taken a molecule of one class or another, impacting clinical care.
Cross-reactivity data from immunoassays specifically targeting designer amphetamine-like and synthetic cannabinoid drugs was collected from multiple published sources, and virtual chemical libraries for molecular similarity analysis were built. The virtual library for synthetic cannabinoid analysis contained a total of 169 structures, while the virtual library for amphetamine-type stimulants contained 288 compounds. Two-dimensional (2D) similarity for each test compound was compared to the target molecule of the immunoassay undergoing analysis.
2D similarity differentiated between cross-reactive and non-cross-reactive compounds for immunoassays targeting mephedrone/methcathinone, 3,4-methylenedioxypyrovalerone, benzylpiperazine, mephentermine, and synthetic cannabinoids.
In this study, we applied 2D molecular similarity analysis to the designer amphetamine-type stimulants and synthetic cannabinoids. Similarity calculations can be used to more efficiently decide which drugs and metabolites should be tested in cross-reactivity studies, as well as to design experiments and potentially predict antigens that would lead to immunoassays with cross reactivity for a broader array of designer drugs.
Full-text · Article · May 2014 · Journal of Cheminformatics
[Show abstract][Hide abstract] ABSTRACT: Background:
Autoverification is a process of using computer-based rules to verify clinical laboratory test results without manual intervention. To date, there is little published data on the use of autoverification over the course of years in a clinical laboratory. We describe the evolution and application of autoverification in an academic medical center clinical chemistry core laboratory.
Subjects and Methods:
At the institution of the study, autoverification developed from rudimentary rules in the laboratory information system (LIS) to extensive and sophisticated rules mostly in middleware software. Rules incorporated decisions based on instrument error flags, interference indices, analytical measurement ranges (AMRs), delta checks, dilution protocols, results suggestive of compromised or contaminated specimens, and ‘absurd’ (physiologically improbable) values.
The autoverification rate for tests performed in the core clinical chemistry laboratory has increased over the course of 13 years from 40% to the current overall rate of 99.5%. A high percentage of critical values now autoverify. The highest rates of autoverification occurred with the most frequently ordered tests such as the basic metabolic panel (sodium, potassium, chloride, carbon dioxide, creatinine, blood urea nitrogen, calcium, glucose; 99.6%), albumin (99.8%), and alanine aminotransferase (99.7%). The lowest rates of autoverification occurred with some therapeutic drug levels (gentamicin, lithium, and methotrexate) and with serum free light chains (kappa/lambda), mostly due to need for offline dilution and manual filing of results. Rules also caught very rare occurrences such as plasma albumin exceeding total protein (usually indicative of an error such as short sample or bubble that evaded detection) and marked discrepancy between total bilirubin and the spectrophotometric icteric index (usually due to interference of the bilirubin assay by immunoglobulin (Ig) M monoclonal gammopathy).
Our results suggest that a high rate of autoverification is possible with modern clinical chemistry analyzers. The ability to autoverify a high percentage of results increases productivity and allows clinical laboratory staff to focus attention on the small number of specimens and results that require manual review and investigation.
[Show abstract][Hide abstract] ABSTRACT: A rapid headspace-gas chromatography (HS-GC) method was developed for the analysis of ethylene glycol and propylene glycol in plasma and serum specimens using 1,3-propanediol as the internal standard. The method employed a single-step derivitization using phenylboronic acid, was linear to 200 mg/dL and had a lower limit of quantitation of 1 mg/dL suitable for clinical analyses. The analytical method described allows for laboratories with HS-GC instrumentation to analyze ethanol, methanol, isopropanol, ethylene glycol, and propylene glycol on a single instrument with rapid switch-over from alcohols to glycols analysis. In addition to the novel HS-GC method, a retrospective analysis of patient specimens containing ethylene glycol and propylene glycol was also described. A total of 36 patients ingested ethylene glycol, including 3 patients who presented with two separate admissions for ethylene glycol toxicity. Laboratory studies on presentation to hospital for these patients showed both osmolal and anion gap in 13 patients, osmolal but not anion gap in 13 patients, anion but not osmolal gap in 8 patients, and 1 patient with neither an osmolal nor anion gap. Acidosis on arterial blood gas was present in 13 cases. Only one fatality was seen; this was a patient with initial serum ethylene glycol concentration of 1282 mg/dL who died on third day of hospitalization. Propylene glycol was common in patients being managed for toxic ingestions, and was often attributed to iatrogenic administration of propylene glycol-containing medications such as activated charcoal and intravenous lorazepam. In six patients, propylene glycol contributed to an abnormally high osmolal gap. The common presence of propylene glycol in hospitalized patients emphasizes the importance of being able to identify both ethylene glycol and propylene glycol by chromatographic methods.