Robustness of a multivariate composite score when evaluating distress of animal models for gastrointestinal diseases

Talbot, Steven R.; Kumstel, Simone; Schulz, Benjamin; Tang, Guanglin; Abdelrahman, Ahmed; Seume, Nico; Wendt, Edgar Heinz Uwe; Eichberg, Johanna; Häger, Christine; Bleich, André; Vollmar, Brigitte; Zechner, Dietmar

doi:10.1038/s41598-023-29623-8

Cited by 5 publications

(1 citation statement)

References 63 publications

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“…Although performed with great care, this study has some shortcomings. Evidence-based severity classification is upcoming and has been performed for different procedures and models, such as epilepsy [ 22 , 23 , 24 ], repeated anesthesia [ 25 , 26 ], depression [ 27 ] and models of gastrointestinal diseases [ 28 ]. Recently, a mathematical model to estimate the severity of animal procedures has been described by Morton [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Severity Classification of Laboratory Animal Procedures in Two Belgian Academic Institutions

Vleeschauwer

Lambaerts

Hernot

et al. 2023

Animals

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According to the EU Directive 2010/63, all animal procedures must be classified as non-recovery, mild, moderate or severe. Several examples are included in the Directive to help in severity classification. Since the implementation of the Directive, different publications and guidelines have been disseminated on the topic. However, due to the large variety of disease models and animal procedures carried out in many different animal species, guidance on the severity classification of specific procedures or models is often lacking or not specific enough. The latter is especially the case in disease models where the level of pain, suffering, distress and lasting harm depends on the duration of the study (for progressive disease models) or the dosage given (for infectious or chemically induced disease models). This, in turn, may lead to inconsistencies in severity classification between countries, within countries and even within institutions. To overcome this, two Belgian academic institutions with a focus on biomedical research collaborated to develop a severity classification for all the procedures performed. This work started with listing all in-house procedures and assigning them to 16 (sub)categories. First, we determined which parameters, such as clinical signs, dosage or duration, were crucial for severity classification within a specific (sub)category. Next, a severity classification was assigned to the different procedures, which was based on professional judgment by the designated veterinarians, members of the animal welfare body (AWB) and institutional animal ethics committee (AEC), integrating the available literature and guidelines. During the classification process, the use of vague terminology, such as ‘minor impact’, was avoided as much as possible. Instead, well-defined cut-offs between severity levels were used. Furthermore, we sought to define common denominators to group procedures and to be able to classify new procedures more easily. Although the primary aim is to address prospective severity, this can also be used to assess actual severity. In summary, we developed a severity classification for all procedures performed in two academic, biomedical institutions. These include many procedures and disease models in a variety of animal species for which a severity classification was not reported so far, or the terms that assign them to a different severity were too vague.

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Section: Discussionmentioning

confidence: 99%

Severity Classification of Laboratory Animal Procedures in Two Belgian Academic Institutions

Vleeschauwer

Lambaerts

Hernot

et al. 2023

Animals

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Continuous monitoring of physiological data using the patient vital status fusion score in septic critical care patients

Ohland,

Jack,

Mast

et al. 2024

Sci Rep

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Accurate and standardized methods for assessing the vital status of patients are crucial for patient care and scientific research. This study introduces the Patient Vital Status (PVS), which quantifies and contextualizes a patient's physical status based on continuous variables such as vital signs and deviations from age-dependent normative values. The vital signs, heart rate, oxygen saturation, respiratory rate, mean arterial blood pressure, and temperature were selected as input to the PVS pipeline. The method was applied to 70 pediatric patients in the intensive care unit (ICU), and its efficacy was evaluated by matching high values with septic events at different time points in patient care. Septic events included systemic inflammatory response syndrome (SIRS) and suspected or proven sepsis. The comparison of maximum PVS values between the presence and absence of a septic event showed significant differences (SIRS/No SIRS: p < 0.0001, η2 = 0.54; Suspected Sepsis/No Suspected Sepsis: p = 0.00047, η2 = 0.43; Proven Sepsis/No Proven Sepsis: p = 0.0055, η2 = 0.34). A further comparison between the most severe PVS in septic patients with the PVS at ICU discharge showed even higher effect sizes (SIRS: p < 0.0001, η2 = 0.8; Suspected Sepsis: p < 0.0001, η2 = 0.8; Proven Sepsis: p = 0.002, η2 = 0.84). The PVS is emerging as a data-driven tool with the potential to assess a patient's vital status in the ICU objectively. Despite real-world data challenges and potential annotation biases, it shows promise for monitoring disease progression and treatment responses. Its adaptability to different disease markers and reliance on age-dependent reference values further broaden its application possibilities. Real-time implementation of PVS in personalized patient monitoring may be a promising way to improve critical care. However, PVS requires further research and external validation to realize its true potential.

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Using weight loss to predict outcome and define a humane endpoint in preclinical sepsis studies

Brochut,

Heinonen,

Snäkä

et al. 2024

Sci Rep

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Preclinical mouse models are critical for understanding the pathophysiological response to infections and developing treatment strategies for sepsis. In keeping with ethical values, researchers follow guidelines to minimize the suffering of the mice. Weight loss is a criteria used as a humane end point, but there is no official recommendation for a maximum weight loss leading to euthanasia. To evaluate whether the thresholds used in daily practice are optimal, we performed a comprehensive retrospective analysis of data generated over 10 years with > 2300 mice used in models of infection with Listeria monocytogenes, Streptococcus pneumoniae, Candida albicans and H1N1 influenza virus. Weight loss segregated mice that survived from those that did not. Statistical analyses revealed that lowering the weight loss thresholds used (none, 30% or 20%) would have increased mortality rates due to the sacrifice of mice that survived infections (p < 0.01–0.001). Power calculations showed high variability and reduction of power as weight loss thresholds approached 20% for S. pneumoniae and L. monocytogenes models. Hence, weight loss thresholds need to be adapted to each model of infection used in a laboratory. Overall, weight loss is a valuable predictor of mortality that contributes to the robustness of composite scores. To our knowledge, this is the most extensive study exploring the relationship between weight loss threshold and sepsis outcome. It underscores the importance of the infection-model-specific evaluation of weight loss for use in clinical scores defining humane endpoints to minimize mouse suffering without compromising statistical power and scientific objectives.

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Robustness of a multivariate composite score when evaluating distress of animal models for gastrointestinal diseases

Cited by 5 publications

References 63 publications

Severity Classification of Laboratory Animal Procedures in Two Belgian Academic Institutions

Severity Classification of Laboratory Animal Procedures in Two Belgian Academic Institutions

Continuous monitoring of physiological data using the patient vital status fusion score in septic critical care patients

Using weight loss to predict outcome and define a humane endpoint in preclinical sepsis studies

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