Factors Affecting the Interpretation of Canine and Nonhuman Primate Clinical Pathology

2003 ◽  
Vol 31 (1_suppl) ◽  
pp. 6-10 ◽  
Author(s):  
Robert L. Hall ◽  
Nancy E. Everds
Keyword(s):  
Study Design ◽  
Nonhuman Primate ◽  
Clinical Chemistry ◽  
Clinical Pathology ◽  
Data Interpretation ◽  
Pharmacokinetic Analysis ◽  
Test Results ◽  
Sample Collection ◽  
Test Species ◽  
Design Variables

Interpreting canine and nonhuman primate clinical pathology data from preclinical studies can be challenging. Relatively few animals are tested (typically beagles and macaques), and they often undergo study-related procedures (eg, sample collection for pharmacokinetic analysis) that can affect clinical pathology test results. Data interpretation requires an understanding of the significance of each test, species differences for each test, normal interanimal and intraanimal variability, the effects of study design variables, and supporting data from other disciplines. Interpretation of hematology, coagulation, clinical chemistry, and urinalysis parameters are discussed, with emphasis on species peculiarities and study design variables that may affect clinical pathology test results.

scholarly journals Deciphering Sources of Variability in Clinical Pathology

2016 ◽  
Vol 45 (1) ◽  
pp. 90-93 ◽  
Author(s):  
Niraj K. Tripathi ◽  
Nancy E. Everds ◽  
A. Eric Schultze ◽  
Armando R. Irizarry ◽  
Robert L. Hall ◽  
...  
Keyword(s):  
Study Design ◽  
Toxicity Testing ◽  
Clinical Pathology ◽  
Data Interpretation ◽  
Potential Effect ◽  
Reference Intervals ◽  
Sample Collection ◽  
Related Factors ◽  
Specimen Handling ◽  
Pathology Data

The objectives of this session were to explore causes of variability in clinical pathology data due to preanalytical and analytical variables as well as study design and other procedures that occur in toxicity testing studies. The presenters highlighted challenges associated with such variability in differentiating test article–related effects from the effects of experimental procedures and its impact on overall data interpretation. These presentations focused on preanalytical and analytical variables and study design–related factors and their influence on clinical pathology data, and the importance of various factors that influence data interpretation including statistical analysis and reference intervals. Overall, these presentations touched upon potential effect of many variables on clinical pathology parameters, including animal physiology, sample collection process, specimen handling and analysis, study design, and some discussion points on how to manage those variables to ensure accurate interpretation of clinical pathology data in toxicity studies. This article is a brief synopsis of presentations given in a session entitled “Deciphering Sources of Variability in Clinical Pathology—It’s Not Just about the Numbers” that occurred at the 35th Annual Symposium of the Society of Toxicologic Pathology in San Diego, California.

scholarly journals Influence of Study Design Variables on Clinical Pathology Data

2016 ◽  
Vol 45 (2) ◽  
pp. 288-295 ◽  
Author(s):  
Adam Aulbach ◽  
Anne Provencher ◽  
Niraj Tripathi
Keyword(s):  
Study Design ◽  
Drug Class ◽  
Clinical Pathology ◽  
Test System ◽  
Test Results ◽  
Design Variables ◽  
Number Of Factors ◽  
Safety Studies ◽  
Animal Care ◽  
Pathology Data

A number of factors related to study design have the potential to impact clinical pathology test results during the conduct of nonclinical safety studies. A thorough understanding of these factors is paramount in drawing accurate conclusions from clinical pathology data generated during such studies, particularly when attempting to make the distinction between test article and nontest article–related effects. Study design and conduct variables with potential to impact clinical pathology data discussed in this overview include those related to species and test system, animal age, animal care and husbandry practices, fasting, acclimatization periods, effects of transportation and stressors, route of administration, effects of in-life and surgical procedures, influence of study length, timing of blood collections, impact of vehicle/formulation composition, and some general concepts related to drug class. The material presented here is a summary based on information presented at the 35th Annual Symposium of the Society of Toxicologic Pathology (June 2016), during Symposium Session 2 titled “Deciphering Sources of Variability in Clinical Pathology—It’s Not Just about the Numbers.”

scholarly journals Clinical Evaluation of the Torq Zero Delay Centrifuge System for Decentralized Blood Collection and Stabilization

Diagnostics ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1019
Author(s):  
Kyungjin Hong ◽  
Gabriella Iacovetti ◽  
Ali Rahimian ◽  
Sean Hong ◽  
Jon Epperson ◽  
...  
Keyword(s):  
Clinical Chemistry ◽  
Blood Collection ◽  
Test Results ◽  
Sample Collection ◽  
Rapid Separation ◽  
Cell Counts ◽  
Collection Device ◽  
Precision Study ◽  
Clinically Significant ◽  
Blood Specimens

Blood sample collection and rapid separation—critical preanalytical steps in clinical chemistry—can be challenging in decentralized collection settings. To address this gap, the Torq™ zero delay centrifuge system includes a lightweight, hand-portable centrifuge (ZDrive™) and a disc-shaped blood collection device (ZDisc™) enabling immediate sample centrifugation at the point of collection. Here, we report results from clinical validation studies comparing performance of the Torq System with a conventional plasma separation tube (PST). Blood specimens from 134 subjects were collected and processed across three independent sites to compare ZDisc and PST performance in the assessment of 14 analytes (K, Na, Cl, Ca, BUN, creatinine, AST, ALT, ALP, total bilirubin, albumin, total protein, cholesterol, and triglycerides). A 31-subject precision study was performed to evaluate reproducibility of plasma test results from ZDiscs, and plasma quality was assessed by measuring hemolysis and blood cells from 10 subject specimens. The ZDisc successfully collected and processed samples from 134 subjects. ZDisc results agreed with reference PSTs for all 14 analytes with mean % biases well below clinically significant levels. Results were reproducible across different operators and ZDisc production lots, and plasma blood cell counts and hemolysis levels fell well below clinical acceptance thresholds. ZDiscs produce plasma samples equivalent to reference PSTs. Results support the suitability of the Torq System for remotely collecting and processing blood samples in decentralized settings.

scholarly journals Practical Considerations in Clinical Pathology Data Interpretation and Description

2016 ◽  
Vol 45 (2) ◽  
pp. 362-365 ◽  
Author(s):  
Robert L. Hall
Keyword(s):  
Safety Assessment ◽  
Clinical Pathology ◽  
Data Interpretation ◽  
Potential Effect ◽  
Reference Intervals ◽  
Standard Approach ◽  
Test Results ◽  
Assessment Study ◽  
Preclinical Safety ◽  
Pathology Data

Although interpretation and description of clinical pathology test results for any preclinical safety assessment study should employ a consistent standard approach, companies differ regarding that approach and the appearance of the end product. Some rely heavily on statistical analysis, others do not. Some believe reference intervals are important, most do not. Some prefer severity of effects be described by percentage differences from, or multiples of, baseline or control, others prefer only word modifiers. Some expect a definitive decision for every potential effect, others accept uncertainty. This commentary addresses these differences and underscores the need for flexibility in a “consistent standard approach” because the conditions of every study are unique. This article constitutes an overview of material originally presented at Session 2 of the 2016 Society of Toxicologic Pathology Annual Symposium.

scholarly journals Comparative Pathologists: Ultimate Control Freaks Seeking Validation!

2018 ◽  
Vol 56 (1) ◽  
pp. 19-23 ◽  
Author(s):  
Krista M. D. La Perle
Keyword(s):  
Experimental Design ◽  
Model Development ◽  
Clinical Pathology ◽  
Scoring Systems ◽  
Data Interpretation ◽  
Tissue Sampling ◽  
Sample Collection ◽  
Slide Preparation ◽  
Histopathologic Evaluation ◽  
Pathology Data

Definable, reproducible, and meaningful are elemental features of grading/scoring systems, while thoroughness, accuracy, and consistency are quality indicators of pathology reports. The expertise of pathologists is significantly underutilized when it is limited to rendering diagnoses. The opportunity to provide guidance on animal model development, experimental design, optimal sample collection, and data interpretation not only contributes to job satisfaction but also, more importantly, promotes validation of the pathology data. Keys to validation include standard operating procedures, experimental controls, and standardized nomenclature applied throughout the experimental design and execution, tissue sampling, and slide preparation, as well as the creation or adaptation and application of semiquantitative grading/scoring systems. Diagnostic drift, thresholds, mental noise, and various diurnal fluctuations strongly influence the repeatability of grading/scoring systems used by the same or different pathologists. Quantitative image analyses are not plagued by the visual and cognitive traps that affect manual semiquantitative grading schemes but may still be affected by technical variables associated with necropsy, tissue sampling, and slide preparation. The validity of a grading scheme is ultimately assessed by its repeatability and biologic relevance, so it is important to correlate scores with comprehensive pathobiology data such as results of antemortem imaging, clinical pathology data, body and organ weights, and histopathologic evaluation of full tissue sets.

scholarly journals The influence of dynamic environmental interactions on detection efficiency of acoustic transmitters in a large, deep, freshwater lake

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Natalie V. Klinard ◽  
Edmund A. Halfyard ◽  
Jordan K. Matley ◽  
Aaron T. Fisk ◽  
Timothy B. Johnson
Keyword(s):  
Study Design ◽  
Environmental Conditions ◽  
Power Output ◽  
Environmental Variables ◽  
Acoustic Telemetry ◽  
Detection Efficiency ◽  
Data Interpretation ◽  
Heterogeneous Environments ◽  
Depth Range ◽  
Dynamic Relationship

Abstract Background Acoustic telemetry is an increasingly common method used to address ecological questions about the movement, behaviour, and survival of freshwater and marine organisms. The variable performance of acoustic telemetry equipment and ability of receivers to detect signals from transmitters have been well studied in marine and coral reef environments to inform study design and improve data interpretation. Despite the growing use of acoustic telemetry in large, deep, freshwater systems, detection efficiency and range, particularly in relation to environmental variation, are poorly understood. We used an array of 90 69-kHz acoustic receivers and 8 sentinel range transmitters of varying power output deployed at different depths and locations approximately 100–9500 m apart for 215 days to evaluate how the detection efficiency of acoustic receivers varied spatially and temporally in relation to environmental conditions. Results The maximum distance that tags were detected ranged from 5.9 to 9.3 km. Shallow tags consistently had lower detection efficiency than deep tags of the same power output and detection efficiency declined through the winter months (December–February) of the study. In addition to the distance between tag and receiver, thermocline strength, surface water velocity, ice thickness, water temperature, depth range between tag and receiver, and number of fish detections contributed to explaining variation in detection efficiency throughout the study period. Furthermore, the most significant models incorporated interactions between several environmental variables and tag–receiver distance, demonstrating the complex temporal and spatial relationships that exist in heterogeneous environments. Conclusions Relying on individual environmental variables in isolation to interpret receiver performance, and thus animal behaviour, may be erroneous when detection efficiency varies across distances, depths, or tag types. As acoustic telemetry becomes more widely used to study ecology and inform management, it is crucial to understand its limitations in heterogeneous environments, such as freshwater lakes, to improve the quality and interpretation of data. We recommend that in situ range testing and retrospective analysis of detection efficiency be incorporated into study design for telemetry projects. Furthermore, we caution against oversimplifying the dynamic relationship between detection efficiency and environmental conditions for the sake of producing a correction that can be applied directly to detection data of tagged animals when the intended correction may not be justified.

Brief Synopsis: “Instruction Manual for Juvenile Clinical Pathology”

2021 ◽  
pp. 019262332110413
Author(s):  
Anne Provencher ◽  
Paula Katavolos
Keyword(s):  
Data Analysis ◽  
Clinical Pathology ◽  
Data Interpretation ◽  
Physiological Functions ◽  
Instruction Manual ◽  
Test Article ◽  
Accurate Interpretation ◽  
Key Points ◽  
Pathology Data

This symposium synopsis summarizes key points discussed related to clinical pathology data interpretation for reproduction and juvenile toxicology studies. In pregnant and growing animals, several changes in clinical pathology parameters linked to growth/maturation of organ and physiological functions can occur, and understanding these changes is important to enable accurate interpretation of clinical pathology data. A brief overview of the general approach to clinical pathology data analysis according to contemporary practices is provided, followed by a discussion focused specifically on reproductive and juvenile clinical pathology. In this context, the approach to recognize and differentiate changes that may be related to pregnancy and growth as opposed to those that may be related to test article effects is highlighted.

scholarly journals Investigation of the Combination of Pregabalin with Duloxetine or Amitriptyline on the Pharmacokinetics and Antiallodynic Effect During Neuropathic Pain in Rats

2021 ◽  
pp. E511-E520
Keyword(s):  
Neuropathic Pain ◽  
Motor Coordination ◽  
Combined Therapy ◽  
Pharmacokinetic Analysis ◽  
Test Results ◽  
Rotarod Test ◽  
Model Study ◽  
Liquid Chromatography Tandem Mass ◽  
Male Wistar Rats ◽  
Antiallodynic Effect

BACKGROUND: Amitriptyline, duloxetine, and pregabalin are among the most pharmacotherapeutic, effective treatments for neuropathic pain control. However, the evaluation of synergism by combining these treatments is still poorly investigated. OBJECTIVES: To evaluate the pharmacokinetics of the combination of pregabalin plus duloxetine and pregabalin plus amitriptyline, as well as the effect of these on neuropathic pain on rodent model. STUDY DESIGN: The experimental study. SETTING: The research took place in the research laboratories at the Federal University of Alfenas after ethics committee approval. METHODS: This study used male Wistar rats weighing between 220 and 250 g. The animals were randomly divided into the following groups: monotherapy (pregabalin, amitriptyline, duloxetine), combined therapy (pregabalin + amitriptyline, pregabalin + duloxetine), and vehicle (ultrapure water). Pharmacokinetic analysis of pregabalin or combination (pregabalin + amitriptyline or pregabalin + duloxetine) in the plasma were performed by ultraperformance liquid chromatography tandem mass spectrometry. Neuropathic pain was induced by sciatic nerve constriction (chronic constriction injury [CCI]) model, and nociceptive threshold was measured by von Frey filaments test. In addition, to evaluate the influence of the treatments on the motor coordination, the rotarod test was used. RESULTS: The pharmacokinetic disposition of pregabalin was changed in the association with amitriptyline, presenting a clearance reduction and consequently an increase in bioavailability. Furthermore, after the 14th day of CCI, pregabalin was administered orally and induced antiallodynic effect after 1, 2:15, 4, and 8 hours of its administration and showed the greatest antiallodynic effect after 4 hours of its administration. Moreover, this effect was prolonged (up to 8 hours) by combination with amitriptyline. Additionally, pregabalin and pregabalin + duloxetine showed a hypoalgesic effect in sham rats. In addition, the rotarod test results showed that drugs did not influence the motor coordination of the rats. LIMITATIONS: Potential competition mechanisms during the excretion of pregabalin, when pregabalin was combined with amitriptyline, were not investigated in this study. CONCLUSIONS: The data demonstrated that combined therapy of pregabalin plus amitriptyline improved the bioavailability of pregabalin and potentiated the efficacy of the antiallodynic effect of pregabalin alone, proving to be advantageous for the treatment of sciatic neuropathic pain. KEY WORDS: Neuropathic pain, pregabalin, duloxetine, amitriptyline, pharmacokinetic, antiallodynic effect, combined therapy, rats

Implementation of a pharmacist-provided pharmacogenomics service in an executive health program

2021 ◽  
Author(s):  
Ina Liko ◽  
Lisa Corbin ◽  
Eric Tobin ◽  
Christina L Aquilante ◽  
Yee Ming Lee
Keyword(s):  
Health Program ◽  
Medical Center ◽  
Academic Medical Center ◽  
Test Results ◽  
Sample Collection ◽  
Team Members ◽  
University Of Colorado ◽  
Academic Medical ◽  
Previous Medication ◽  
Selection Of

Abstract Disclaimer In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose We describe the implementation of a pharmacist-provided pharmacogenomics (PGx) service in an executive health program (EHP) at an academic medical center. Summary As interest in genomic testing grows, pharmacists have the opportunity to advance the use of PGx in EHPs, in collaboration with other healthcare professionals. In November 2018, a pharmacist-provided PGx service was established in the EHP at the University of Colorado Hospital. The team members included 3 physicians, a pharmacist trained in PGx, a registered dietitian/exercise physiologist, a nurse, and 2 medical assistants. We conducted 4 preimplementation steps: (1) assessment of the patient population, (2) selection of a PGx test, (3) establishment of a visit structure, and (4) selection of a billing model. The PGx consultations involved two 1-hour visits. The first visit encompassed pretest PGx education, review of the patient’s current medications and previous medication intolerances, and DNA sample collection for genotyping. After this visit, the pharmacist developed a therapeutic plan based on the PGx test results, discussed the results and plan with the physician, and created a personalized PGx report. At the second visit, the pharmacist reviewed the PGx test results, personalized the PGx report, and discussed the PGx-guided therapeutic plan with the patient. Overall, the strategy worked well; minor challenges included evaluation of gene-drug pairs with limited PGx evidence, communication of information to non-EHP providers, scheduling issues, and reimbursement. Conclusion The addition of a PGx service within an EHP was feasible and provided pharmacists the opportunity to lead PGx efforts and collaborate with physicians to expand the precision medicine footprint at an academic medical center.

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