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Background: Reliable animal models are critical for preclinical research and should closely mimic the disease. With respect to route of infection, pathogenic agent, disease progression, clinical signs, and histopathological changes. Sheep have similar bone micro- and macrostructure as well as comparable biomechanical characteristics to humans. Their use in bone research is established, however their use in bone infection research is limited. This systematic review will summarise the key features of the available bone infection models using sheep, providing a reference for further development, validation, and application. Method: This systematic review was designed according to the PRISMA guidelines and registered with PROSPERO. Quality was assessed using SYRICLE's risk of bias tool adapted for animal studies. PubMed, MEDLINE, Web of Science and EMBASE were searched until March 2022.1921 articles were screened by two independent reviewers, and 25 were included for analysis. Results: Models have been developed in nine different breeds. Staphylococcus aureus was used in the majority of models, typically inoculating 108 colony forming units in tibial or femoral cortical defects. Infection was established with either planktonic or biofilm adherent bacteria, with or without foreign material implanted. Most studies used both radiological and microbiological analyses to confirm osteomyelitis. Conclusions: There is convincing evidence supporting the use of sheep in bone infection models of clinical disease. The majority of sheep studied demonstrated convincing osteomyelitis and tolerated the infection with minimal complications. Furthermore, the advantages of comparable biology and biomechanics may increase the success for translating in vivo results to successful therapies. The Translational potential of this article: In the realm of preclinical research, the translation to viable clinical therapies is often perilous, and the quest for reliable and representative animal models remains paramount. This systematic review accentuates the largely untapped potential of sheep as large animal models, especially in bone infection research. The anatomical and biomechanical parallels between sheep and human bone structures position sheep as an invaluable asset for studying osteomyelitis and periprosthetic joint infection. This comprehensive exploration of the literature demonstrates the robustness and translational promise of these models. Furthermore, this article underscores the potential applicability for sheep in developing effective therapeutic strategies for human bone infections.
RESUMEN
BACKGROUND: Cognitive or communication issues may preclude direct modified Rankin Scale interview, necessitating interview with a suitable surrogate. The clinimetric properties of this proxy modified Rankin Scale assessment have not been described. AIMS: To describe reliability of proxy-derived modified Rankin Scale and compare with traditional direct patient interview. METHODS: Researchers assessed consenting stroke inpatients and their proxies using a nonstructured modified Rankin Scale approach. Paired interviewers (trained in modified Rankin Scale) performed independent and blinded modified Rankin Scale assessment of patients and appropriate proxies. Interobserver variability and agreement between patient and proxy modified Rankin Scale were described using kappa statistics (k, 95% confidence interval) and percentage agreement. RESULTS: Ninety-seven stroke survivors were assessed. Proxies were family members (n = 29), nurses (n = 50), or physiotherapists (n = 25). Median modified Rankin Scale from both patient and proxies was 3 [interquartile range (IQR): 2-4]. Reliability for patient modified Rankin Scale interview was weighted kappa = 0·70 (95% confidence interval: 0·30-1·00). Reliability for proxy modified Rankin Scale weighted kappa = 0·62 (95% confidence interval: 0·34-0·90). Subgroup analysis of various proxy information sources were as follows: family weighted kappa = 0·61; nurse weighted kappa = 0·58; therapist weighted kappa = 0·58. There was disagreement between patient-derived modified Rankin Scale and corresponding proxy modified Rankin Scale weighted kappa = 0·64 (95% CI: 0·42-0·86). CONCLUSIONS: There is potential for substantial interobserver variability in proxy modified Rankin Scale and validity of certain proxy assessments is questionable. Direct modified Rankin Scale interview is preferred.
