Safety and efficacy of fumagillin for the treatment of intestinal microsporidiosis. A French prospective cohort study.

BACKGROUND: Intestinal microsporidiosis due to Enterocytozoon bieneusi is a cause of chronic diarrhoea in immunocompromised patients. Fumagillin has been approved in France for its treatment. OBJECTIVES: To investigate the efficacy and safety of fumagillin in a real-life setting. METHODS: As required by the French Medicine Agency, all patients receiving fumagillin were enrolled in a prospective study to evaluate its efficacy and safety. Stool examination with identification of E. bieneusi by PCR was performed at baseline, end of treatment and monthly thereafter for 6 months. Safety was monitored up to 6 months and full blood counts were monitored up to 42 days after treatment initiation. The primary endpoint was safety. Parasite clearance and relapses were secondary endpoints. RESULTS: From 2007 to 2018, 166 patients received fumagillin, including 6 children. Patients were transplant recipients (84%), HIV-infected patients (13%) or had another cause of immunosuppression (5%). Serious adverse events were reported in 41 patients (25%), mainly thrombocytopenia (15%) and neutropenia (5%), with two haemorrhagic events leading to one death. Severe thrombocytopenia (<50 G/L) developed in 50 patients (29.6%), neutropenia (<1 G/L) in 20 patients (11.8%) and severe anaemia (<8 g/dL) in 21 patients (12.4%). At the end of treatment, 94% of patients with available stool examination (n = 132) had no spores detected. Among 99 patients with available follow-up after the end of treatment, three parasite relapses were documented. CONCLUSIONS: E. bieneusi microsporidiosis was mainly diagnosed in transplant recipients. Fumagillin was associated with haematological toxicity but showed high efficacy with a low relapse rate.

Prediction of all-cause mortality in haemodialysis patients using a Bayesian network.

BACKGROUND: All-cause mortality in haemodialysis (HD) is high, reaching 15.6% in the first year according to the European Renal Association. METHODS: A new clinical tool to predict all-cause mortality in HD patients is proposed. It uses a post hoc analysis of data from the prospective cohort study Photo-Graph V3. A total of 35 variables related to patient characteristics, laboratory values and treatments were used as predictors of all-cause mortality. The first step was to compare the results obtained using a logistic regression to those obtained by a Bayesian network. The second step aimed to increase the performance of the best prediction model using synthetic data. Finally, a compromise between performance and ergonomics was proposed by reducing the number of variables to be entered in the prediction tool. RESULTS: Among the 9010 HD patients included in the Photo-Graph V3 study, 4915 incident patients with known medical status at 2 years were analysed. All-cause mortality at 2 years was 34.1%. The Bayesian network provided the most reliable prediction. The final optimized models that used 14 variables had areas under the receiver operating characteristic curves of 0.78 ± 0.01, sensitivity of 72 ± 2%, specificity of 69 ± 2%, predictive positive value of 70 ± 1% and negative predictive value of 71 ± 2% for the prediction of all-cause mortality. CONCLUSIONS: Using artificial intelligence methods, a new clinical tool to predict all-cause mortality in incident HD patients is proposed. The latter can be used for research purposes before its external validation at: https://www.hed.cc/? a=twoyearsallcausemortalityhemod&n=2-years%20All-cause%20Mortality%20Hemodialysis.neta.