Results Of Clinical Chemistry Tests Research Articles

Combined strategy of knowledge-based rule selection and historical data percentile-based range determination to improve an autoverification system for clinical chemistry test results.

BackgroundCurrent autoverification, which is only knowledge‐based, has low efficiency. Regular historical data analysis may improve autoverification range determination. We attempted to enhance autoverification by selecting autoverification rules by knowledge and ranges from historical data. This new system was compared with the original knowledge‐based system.MethodsNew types of rules, extreme values, and consistency checks were added and the autoverification workflow was rearranged to construct a framework. Criteria for creating rules for extreme value ranges, limit checks, consistency checks, and delta checks were determined by analyzing historical Zhongshan laboratory data. The new system's effectiveness was evaluated using pooled data from 20 centers. Efficiency improvement was assessed by a multicenter process.ResultsEffectiveness was evaluated by the true positive rate, true negative rate, and overall consistency rate, as compared to manual verification, which were 77.55%, 78.53%, and 78.3%, respectively for the new system. The original overall consistency rate was 56.2%. The new pass rates, indicating efficiency, were increased by 19%‒51% among hospitals. Further customization using individualized data increased this rate.ConclusionsThe improved system showed a comparable effectiveness and markedly increased efficiency. This transferable system could be further improved and popularized by utilizing historical data from each hospital.

Clinical Application of Overlapping Confidence Intervals for Monitoring Changes in Serial Clinical Chemistry Test Results.

BackgroundInterpretation of changes in serial laboratory results is necessary for both clinicians and laboratories; however, setting decision limits is not easy. Although the reference change value (RCV) has been widely used for auto-verification, it has limitations in clinical settings. We introduce the concept of overlapping confidence intervals (CIs) to determine whether the changes are statistically significant in clinical chemistry laboratory test results.MethodsIn total, 1,202,096 paired results for 33 analytes routinely tested in our clinical chemistry laboratory were analyzed. The distributions of delta% absolute values and cut-off values for certain percentiles were calculated. The CIs for each analyte were set based on biological variation, and data were analyzed at various confidence levels. Additionally, we analyzed the data using RCVs and compared their clinical utility.ResultsMost analytes had low indexes of individuality with large inter-individual variability. The 97.5th percentile cut-offs for each analyte were much larger than conventional RCVs. The percentages of results exceeding RCV95% and RCV99% corresponded to those with no overlap at the 83.4% and 93.2% confidence levels, respectively.ConclusionsThe use of overlapping CIs in serial clinical chemistry test results can overcome the limitations of existing RCVs and replace them, especially for analytes with large intra-individual variation.

Gentamicin and Vancomycin Interference on Results of Clinical Chemistry Parameters on Abbott Architect c8000.

Gentamicin and vancomycin are nephrotoxic antibiotics. Little is known about the influence of drug concentrations on results of clinical chemistry tests. To investigate gentamicin and vancomycin interference on results of 33 commonly measured biochemistry tests. The study was carried out in the University Department of Chemistry, Medical School University Hospital Sestre Milosrdnice (Zagreb, Croatia). For each drug, 10 aliquots of pooled serum were prepared. In order to cover toxic concentrations, pool serum samples were spiked with drugs to obtain 0 to 50 μg/mL of gentamicin and 0 to 200 μg/mL of vancomycin. Biochemistry tests were measured in duplicate on the Architect c8000 analyzer, and drug concentrations were measured on Architect i2000 SR (both Abbott Laboratories, Abbott Park, Illinois). For each tested concentration, bias was calculated against the initial measurement. Acceptance criteria were defined as measurement uncertainty of the commercial control with the value close to the measured range of the pool sample. For gentamicin, all bias values were below established criteria. For vancomycin, significant changes were observed for potassium, direct bilirubin, and immunoglobulin A. Significant bias was already detected at low vancomycin concentration (2.98 μg/mL) for direct bilirubin (bias = 9.7%; acceptable = 8%). Potassium bias at the highest vancomycin concentration (204.4 μg/mL) exceeded acceptance criteria (bias = 4.5%; acceptable = 4%). For immunoglobulin A, no apparent trend was observed, and bias is attributed to increased method imprecision. Gentamicin did not interfere with the results of clinical chemistry tests. Direct bilirubin concentration is falsely increased in the presence of vancomycin, and potassium is affected at high concentrations.

Presentation of clinical laboratory results: an experimental comparison of four visualization techniques

ObjectiveTo evaluate how clinical chemistry test results were assessed by volunteers when presented with four different visualization techniques.Materials and methodsA total of 20 medical students reviewed quantitative test results from 4 patients using 4 different visualization techniques in a balanced, crossover experiment. The laboratory data represented relevant patient categories, including simple, emergency, chronic and complex patients. Participants answered questions about trend, overall levels and covariation of test results. Answers and assessment times were recorded and participants were interviewed on their preference of visualization technique.ResultsAssessment of results and the time used varied between visualization techniques. With sparklines and relative multigraphs participants made faster assessments. With relative multigraphs participants identified more covarying test results. With absolute multigraphs participants found more trends. With sparklines participants more often assessed laboratory results to be within reference ranges. Different visualization techniques were preferred for the four different patient categories. No participant preferred absolute multigraphs for any patient.DiscussionAssessments of clinical chemistry test results were influenced by how they were presented. Importantly though, this association depended on the complexity of the result sets, and none of the visualization techniques appeared to be ideal in all settings.ConclusionsSparklines and relative multigraphs seem to be favorable techniques for presenting complex long-term clinical chemistry test results, while tables seem to suffice for simpler result sets.

Oromucosal Δ 9-tetrahydrocannabinol/cannabidiol for neuropathic pain associated with multiple sclerosis: An uncontrolled, open-label, 2-year extension trial

Background: Central neuropathic pain (CNP), pain initiated or caused by a primary lesion or dysfunction of the central nervous system, occurs in ~28% of patients with multiple sclerosis (MS). Δ 9-Tetrahydrocannabinol/cannabidiol (THC/CBD), an endocannabinoid system modulator, has demonstrated efficacy for up to 4 weeks in randomized controlled trials in the treatment of CNP in patients with MS. Objective: The purpose of this extension was to establish long-term tolerability and effectiveness profiles for THC/CBD (Sativex ®, GW Pharmaceuticals plc, Salisbury, United Kingdom) oromucosal spray in CNP associated with MS. Methods: This uncontrolled, open-label trial was an indefinite-duration extension of a previously reported 5-week randomized study in patients with MS and CNP. In the initial trial, patients were randomized to placebo or THC/CBD. Patients were only required to maintain their existing analgesia in the randomized study. In the open-label trial they could vary their other analgesia as required. All patients (placebo and THC/CBD) who completed the randomized trial commenced the open-label follow-up on THC/CBD (27 mg/mL: 25 mg/mL). Patients titrated their dosage, maintaining their existing analgesia. The primary end point of the trial was the number, frequency, and type of adverse events (AEs) reported by patients. Secondary end points included changes from baseline in 11-point numerical rating scale (NRS-11) neuropathic pain score, hematology and clinical chemistry test results, vital signs, trial drug usage, and intoxication visual analogue scale scores. Results: Sixty-six patients were enrolled in the randomized trial; 64 (97%) completed the randomized trial and 63 (95%) entered the open-label extension (race, white, 100%; sex, male, 14 [22%]; mean [SD] age, 49 [8.4] years [range, 27–71 years[). The mean (SD) duration of open-label treatment was 463 (378) days (median, 638 days; range, 3–917 days), with 34 (54%) patients completing >1 year of treatment with THC/CBD and 28 (44%) patients completing the open-label trial with a mean (SD) duration of treatment of 839 (42) days (median, 845 days; range, 701–917 days). Mean NRS-11 pain scores in the final week of the randomized trial were 3.8 in the treatment group and 5.0 in the placebo group. In the 28 (44%) patients who completed the 2-year follow up, the mean (SD) NRS-11 pain score in the final week of treatment was 2.9 (2.0) (range, 0-8.0). Fifty-eight (92%) patients experienced ≥1 treatment-related AE. These AEs were rated by the investigator as mild in 47 (75%) patients, moderate in 49 (78%), and severe in 32 (51%). The most commonly reported AEs were dizziness (27%), nausea (18 %), and feeling intoxicated (11%). Two treatmentrelated serious AEs (ventricular bigeminy and circulatory collapse) were judged to be treatment-related. Both serious AEs occurred in the same patient and resolved completely following a period of discontinuation. Eleven (17%) patients experienced oral discomfort, 4 persistently. Regular oral examinations revealed that 7 (11%) patients developed white buccal mucosal patches and 2 (3%) developed red buccal mucosal patches; all cases were deemed mild and resolved. Seventeen (25%) patients withdrew due to AEs. The mean number of sprays and patients experiencing intoxication remained stable throughout the follow-up trial. Conclusions: THC/CBD was effective, with no evidence of tolerance, in these select patients with CNP and MS who completed ∼2 years of treatment (n = 28). Ninety-two percent of patients experienced an AE, the most common of which were dizziness and nausea. The majority of AEs were deemed to be of mild to moderate severity by the investigators.

Serum markers detect the presence of liver fibrosis: A cohort study

Histologic examination of a liver biopsy specimen is regarded as the reference standard for detecting liver fibrosis. Biopsy can be painful and hazardous, and assessment is subjective and prone to sampling error. We developed a panel of sensitive automated immunoassays to detect matrix constituents and mediators of matrix remodeling in serum to evaluate their performance in the detection of liver fibrosis. In an international multicenter cohort study, serum levels of 9 surrogate markers of liver fibrosis were compared with fibrosis stage in liver biopsy specimens obtained from 1021 subjects with chronic liver disease. Discriminant analysis of a test set of samples was used to identify an algorithm combining age, hyaluronic acid, amino-terminal propeptide of type III collagen, and tissue inhibitor of matrix metalloproteinase 1 that was subsequently evaluated using a validation set of biopsy specimens and serum samples. The algorithm detected fibrosis (sensitivity, 90%) and accurately detected the absence of fibrosis (negative predictive value for significant fibrosis, 92%; area under the curve of a receiver operating characteristic plot, .804; standard error, .02; P < .0001; 95% confidence interval, .758-.851). Performance was excellent for alcoholic liver disease and nonalcoholic fatty liver disease. The algorithm performed equally well in comparison with each of the pathologists. In contrast, pathologists' agreement over histologic scores ranged from very good to moderate (kappa = .97-.46). Assessment of liver fibrosis with multiple serum markers used in combination is sensitive, specific, and reproducible, suggesting they may be used in conjunction with liver biopsy to assess a range of chronic liver diseases.

Use of a computer to analyse data from a children's hospital clinical chemistry laboratory

This paper reports attempts to make results of clinical chemistry tests carried out on children more meaningful. Results of tests performed on the initial blood sample obtained from patients over an 18-mth period were transferred to punch cards and processed on a Burroughs 500 Computer using programmes written by one of us (F.L.M.). Patients were classified according to age, sex and location, and specimens according to nature of blood collection and time of day. The initial print-out of each test showed the number and percentage of patients with each result and the cumulative percentage over each range observed. The study has provided previously unknown information about results obtained by the laboratory and has assisted in deriving reference ranges for various groups within the hospital population. By liaison with the Medical Records Department, diagnoses of patients with extreme values and the pattern of findings in particular disorders have been obtained. This paper reports attempts to make results of clinical chemistry tests carried out on children more meaningful. Results of tests performed on the initial blood sample obtained from patients over an 18-mth period were transferred to punch cards and processed on a Burroughs 500 Computer using programmes written by one of us (F.L.M.). Patients were classified according to age, sex and location, and specimens according to nature of blood collection and time of day. The initial print-out of each test showed the number and percentage of patients with each result and the cumulative percentage over each range observed. The study has provided previously unknown information about results obtained by the laboratory and has assisted in deriving reference ranges for various groups within the hospital population. By liaison with the Medical Records Department, diagnoses of patients with extreme values and the pattern of findings in particular disorders have been obtained.