Cushing's syndrome due to interaction between ritonavir or cobicistat and corticosteroids: a case-control study in the French Pharmacovigilance Database.

OBJECTIVES: To explore the frequent interaction between antiretroviral-boosting agents and corticosteroids causing Cushing's syndrome (CS) in the French Pharmacovigilance Database (FPVD). METHODS: We conducted a retrospective case-control study describing CS recorded in the FPVD between 1996 and 2018. Case was defined as CS occurring in people living with HIV (PLWH) and control was defined as CS in uninfected individuals. Drug-drug interaction (DDI) was defined as an interaction between corticosteroids and CYP3A4 inhibitors. Data concerning the DDI, corticosteroids involved, route of administration and seriousness of the CS were described. RESULTS: Among the 139 instances of CS identified, 34/35 cases (97%) had DDIs (31 with ritonavir and 3 with cobicistat) and 7/104 controls (7%) had DDIs (6 with itraconazole and 1 with verapamil). The main corticosteroid involved was inhaled fluticasone (28/35, 80%) among the cases and oral prednisone (38/104, 37%) among the controls. More CS cases (30/35, 86%) than CS controls (62/104, 60%) were serious (OR = 4.0, 95% CI = 1.4-14.4; P = 0.007). CONCLUSIONS: Antiretroviral-boosting agents were responsible for one out of four iatrogenic CS cases in a French national database. Prescribers should be aware of the risk of potentially serious DDIs between antiretroviral-boosting agents and corticosteroids, including single-tablet regimens containing cobicistat.

Improvement of patient care through hirudotherapy and the management of leeches from their reception to their disposal in France.

OBJECTIVE: Medicinal leech therapy - known as hirudotherapy (HT) - is an empirical medical technique that has become popular again in reconstructive surgery. However, at each step of leech management there are risks for blood contamination of the caregivers and severe infections for patients. This reduces the success of the treatment. The aim of this study was to improve the management of leeches from ordering to disposal to improve patient care. METHODS: First, a review of the literature was performed. Second, we conducted a retrospective study of patients' antibiotic prophylaxis from January 2018 to December 2019. The data we collected were patient characteristics, the specific care unit at the hospital, indication, contra-indication, posology, duration of HT, number of leeches delivered, antibiotic prophylaxis prescribed and microbial organism, if identified. Third, an interdisciplinary meeting was organised to review the entire leech circuit: ordering, maintenance, prescription, dispensing, application and disposal. RESULTS: At the end of the literature review, six articles based on practices implemented in France were selected for inclusion. These articles discussed antibiotic prophylaxis, iron supplementation, and leech storage, application and disposal. On the retrospective study performed, antibiotic prophylaxis for HT was performed for 60% (30/50) of patients, 77% (23/30) of the prescriptions followed the recommendations for antibiotic prophylaxis, and 20 patients did not receive antibiotic prophylaxis. The interdisciplinary meeting made it possible to define a collegially validated protocol, containing a computerised antibiotic prophylaxis prescription, including per os ciprofloxacin antibiotic prophylaxis, intravenous iron supplementation and biological monitoring. A leech application protocol was created, and the method of leech disposal was revised. CONCLUSION: Despite the absence of clear guidelines and heterogeneous practices, this study reveals the importance of a standard procedure including leech management practices before use, antibiotic prophylaxis and application and disposal guides. The interdisciplinary protocol allows improved patient care management and makes leech management safer for caregivers.