Detecting horses' sickness: In search of visible signs

International audienceAssessing sickness in animals, by which we refer to non-specific states involving both physical discomfort and negative emotional states, is a real challenge. In this review, we demonstrate the need for clear and simple indicators of sickness in horses, a species in which suffering is largely underestimated. We provide a critical review of existing tools available to assess sickness in equids, which include composite pain scales and scores and welfare assessment scoring. Many such scales and scoring systems involve subjective assessments and lack of clear definitions. We discuss possible objective, visible indicators (qualitative and quantitative behavioural modifications and some postures) associated with sickness in horses, highlighting the two predominant modalities of expression (becoming unresponsive to environmental stimuli and “lethargic”, or becoming aggressive and hostile). Much work is still needed before an agreement can be achieved on the indicators of sickness in horses; there are however signs that, even if non-specific, should attract the owners’ attention on the horses’ welfare state

Drug Interaction between Sirolimus and Ranolazine in a Kidney Transplant Patient

Purpose. The case of a kidney transplant recipient who experienced a probable drug interaction between sirolimus and ranolazine is reported. Summary. The narrow therapeutic window of immunosuppressive therapy in transplant recipients requires close monitoring for potential drug-drug interactions. The patient, a 57-year-old Caucasian male kidney transplant recipient, was stable for years on sirolimus as his primary immunosuppressive agent and had a history of chronic angina, for which he was prescribed ranolazine. Upon addition and dose escalation of ranolazine, whole blood sirolimus levels more than tripled, rising to immeasurably high concentrations. After holding sirolimus on multiple occasions and reducing dosage more than 50%, blood levels returned to therapeutic range, while continuing ranolazine. Conclusion. Since ranolazine is a documented P-GP and CYP3A inhibitor, and sirolimus a known substrate for both pathways, it is proposed that ranolazine inhibition of P-GP and CYP3A4 contributed to the significant elevation in sirolimus exposure. No alternative causes for the rise in sirolimus exposure were found, and assessment with the Drug Interaction Probability Scale finds this interaction to be probable. Clinicians should be aware of the potential for this interaction to cause elevated sirolimus exposure and subsequent increase in clinical effect or toxicity, in this case overimmunosuppression

Improved kidney function and one-year survival with transitioning from intravenous to enteral tacrolimus in lung transplant recipients

Background: Acute kidney injury (AKI) is common after lung transplant and may increase risk of chronic kidney disease (CKD). Calcineurin inhibitors (CNIs) such as tacrolimus contribute to AKI risk. This study evaluated outcomes among lung transplant recipients administered enteral or oral versus intravenous (IV) tacrolimus immediately post-lung transplant. Methods: We performed a single-center retrospective study of lung transplant recipients from 2011 to 2019. Tacrolimus concentrations, rates of perioperative AKI, CKD, and one-year survival were compared between those that received IV versus oral tacrolimus post-LT. Results: A total of 153 patients were included; 110 and 43 received IV tacrolimus and enteral or oral tacrolimus, respectively. AKI within 14 days post-LT occurred more frequently in patients that received IV tacrolimus versus enteral administration (84.5 vs 44.1 %, p = <0.001). Additionally, those patients that received IV tacrolimus had supratherapeutic tacrolimus concentrations for more days than those that received enteral (3 days, IQR 1–5 vs 1 day, IQR 0–1; p < 0.001). CKD rates at 1 year were not significantly different between groups. One year survival was 97.7 % in group that received enteral tacrolimus compared to 82.7 % in IV tacrolimus group (p = 0.01) Conclusion: IV tacrolimus in the initial period post-LT was associated with higher AKI rates and lower 1-year survival compared to enteral tacrolimus. There was no difference in CKD rates at 1 year