Performance of Mucorales spp. qPCR in bronchoalveolar lavage fluid for the diagnosis of pulmonary mucormycosis.

To estimate the diagnostic performance of Mucorales polymerase chain reaction (PCR) in Bronchoalveolar lavage fluid (BALF) in routine practice. This was a single-center retrospective study including all consecutive patients >18 years who underwent Mucorales PCR assay in BALF between January 2021 and May 2022. Index testing was prospectively performed using the MycoGENIE Aspergillus spp.-Mucorales spp. PCR. The reference was the diagnosis of pulmonary mucormycosis by the Adjudication Committee. Mucorales PCR in BALF was performed for 938 patients and was positive for 21 of 938 (2.2%). Eleven pulmonary mucormycosis (including one disseminated) were diagnosed. Among them, one (9.1%) was classified as proven mucormycosis, three (27.3%) as probable, and seven (63.6%) as possible according to the EORTC/MSGERC 2019 criteria. The main host factor was hematological malignancy (10 of 11, 90.9%). Mucorales PCR was positive in serum for eight patients (72.7%). Three patients had positive PCR in BALF, but negative in serum. The mean cycle threshold value was significantly lower in mucormycosis than false-positive cases. Sensitivity was 72.7% (95% confidence interval [CI], 43.4-90.3%), and specificity was 98.6% (95% CI, 97.6-99.2%). The positive and negative predictive values were 38.1% (95% CI, 20.8-59.1%) and 99.7% (95% CI, 99.1-99.9%), respectively. Mucorales PCR in BALF showed good diagnostic performance for mucormycosis, particularly in combination with serum PCR. A positive result should be interpreted with caution, given the possibility of carriage in the airway. However, its high negative predictive value and specificity suggest the utility of Mucorales PCR in BALF in the diagnosis of pulmonary mucormycosis.

Measurement of the Immunosuppressant Possession Ratio by Transplant Clinical Pharmacists Captures a Non-Adherence Associated With Antibody-Mediated Rejection.

Our objective was to calculate an immunosuppressant possession ratio (IPR) to diagnose non-adherence at the time of antibody-mediated rejection (ABMR). IPR was defined as the ratio of number of pills collected at the pharmacy to the number of pills prescribed over a defined period. In a first cohort of 91 kidney transplant recipients (KTRs), those with an IPR < 90% had more frequently a tacrolimus through level coefficient of variation >30% than patients with an IPR = 100% (66.7% vs. 29.4%, p = 0.05). In a case-control study, 26 KTRs with ABMR had lower 6 months IPRs than 26 controls (76% vs. 99%, p < 0.001). In KTRs with ABMR, non-adherence was more often diagnosed by a 6 months IPR < 90% than by clinical suspicion (73.1% vs 30.8%, p = 0.02). In the multivariable analysis, only de novo DSA and 6 months IPR < 90% were independently associated with ABMR, whereas clinical suspicion was not (odds ratio, 4.73; 95% CI, 1.17-21.88; p = 0.03; and odds ratio, 6.34; 95% CI, 1.73-25.59; p = 0.007, respectively). In summary, IPR < 90% is a quantifiable tool to measure immunosuppressant non-adherence. It is better associated with ABMR than clinical suspicion of non-adherence.

Benefit of a pharmacist-led intervention for medication management of renal transplant patients: a controlled before-and-after study.

AIMS: To assess the effect of a pharmacist-led intervention, using Barrows cards method, during the first year after renal transplantation, on patient knowledge about their treatment, medication adherence and exposure to treatment in a French cohort. METHODS: We conducted a before-and-after comparative study between two groups of patients: those who benefited from a complementary pharmacist-led intervention [intervention group (IG), n = 44] versus those who did not [control group (CG), n = 48]. The pharmacist-led intervention consisted of a behavioral and educational interview at the first visit (visit 1). The intervention was assessed 4 months later at the second visit (visit 2), using the following endpoints: treatment knowledge, medication adherence [proportion of days covered (PDC) by immunosuppressive therapy] and tacrolimus exposure. RESULTS: At visit 2, IG patients achieved a significantly higher knowledge score than CG patients (83.3% versus 72.2%, p = 0.001). We did not find any differences in treatment exposure or medication adherence; however, the intervention tended to reduce the proportion of non-adherent patients with low knowledge scores. Using the PDC by immunosuppressive therapy, we identified 10 non-adherent patients (10.9%) at visit 1 and six at visit 2. CONCLUSIONS: Our intervention showed a positive effect on patient knowledge about their treatment. However, our results did not show any improvement in overall medication adherence, which was likely to be because of the initially high level of adherence in our study population. Nevertheless, the intervention appears to have improved adherence in non-adherent patients with low knowledge scores.

Ifosfamide-induced encephalopathy: Brand-name (HOLOXAN®) vs generic formulation (IFOSFAMIDE EG®).

WHAT IS KNOWN AND OBJECTIVE: Two forms of ifosfamide are commercially available in France: HOLOXAN® (brand-name drug) and IFOSFAMIDE EG® (generic drug). Following the marketing launch of the generic drug, there has been a significant increase in cases of ifosfamide-induced encephalopathy reported in France. Our objective is to compare the incidence of ifosfamide-induced encephalopathy in adult patients treated with HOLOXAN® or IFOSFAMIDE EG®. METHODS: This is a retrospective study of adult patients treated with ifosfamide in two medical centers from 2013 to 2017, with data analysed from medical records. Comparisons of patients were made, according to the formulation used and according to the occurrence of ifosfamide-induced encephalopathy. The groups of patients were compared using a chi-square or Fisher's exact test for qualitative parameters and a Wilcoxon test for quantitative parameters. To include confounding factors in the analysis of the impact of drug formulation on the occurrence of ifosfamide-induced encephalopathy, a generalized linear model was performed with the occurrence of ifosfamide-induced encephalopathy as the dependent parameter, and the formulation and the confounding factors as explanatory parameters. RESULTS AND DISCUSSION: A total of 191 patients were included: 103 patients received HOLOXAN® (53.9%) and 88 patients received IFOSFAMIDE EG® (46.1%). In the HOLOXAN® group, the median infusion time was higher (12 hours vs 3h, P < 0.001) and aprepitant was administered more frequently (78.6% vs 69.7%, P < 0.001) than for the IFOSFAMIDE EG® group. Ifosfamide-induced encephalopathy occurred in 11 patients (5.8%, CI 95% [2.9%, 10.0%]). In the ifosfamide-induced encephalopathy group, median infusion time was higher (12 hours [12; 24] vs 3 hours [2; 12] P < 0.001) and a poor performance status was more frequent (54.5% vs 13.9%, P = 0.002) than in the group without ifosfamide-induced encephalopathy. The frequency of ifosfamide-induced encephalopathy in the HOLOXAN® group was 1.9% (2/103) against 10.2% (9/88) in the IFOSFAMIDE EG® group (P = 0.014). Multivariate analysis revealed that treatment with IFOSFAMIDE EG® resulted in significantly more ifosfamide-induced encephalopathies compared to HOLOXAN® (OR and CI 95%:7.4 [1.4; 39.5], P = 0.018). We identified two other risk factors for ifosfamide-induced encephalopathy: long-term infusion and a performance status of two or higher. WHAT IS NEW AND CONCLUSION: The formation of chloroethylamine in solution could be the cause of more frequent ifosfamide-induced encephalopathies with IFOSFAMIDE EG® compared to HOLOXAN®. Application of these data could help in the choice of ifosfamide formulation in adult patients to decrease the risk of ifosfamide-induced encephalopathy, and more specifically for patients with risk factors.

The effect of intravenous isosorbide dinitrate in acute decompensated heart failure in hospital.

Background According to new recommendations for the management of acute decompensated heart failure (ADHF) in 2015, intravenous vasodilator therapy might be given as an early therapy when systolic blood pressure is normal to high (≥110 mmHg). Only 29% of patients with ADHF are treated with vasodilators without medical contraindication. Objective To evaluate the effect of the systematic use of ISDN on ADHF without contraindication especially on rehospitalization rate. Settings The 600-bed hospital (Centre Hospitalier de l'Ouest Vosgien, Neufchâteau, France). Methods This is a retrospective study with data analysed from medical records. Patients with ADHF episodes and hospitalization in the cardiology department or intensive care unit (ICU) between November 2013 and December 2015 were included resulting in 199 hospitalizations in the analysis (37 were treated by ISDN, and 162 were not). Main outcome measure Effects of ISDN on 180-day hospital readmission for ADHF or acute myocardial infarction (AMI), in-hospital mortality, length of stay, number of ICU admissions, and ICU length of stay. Results Patients who received ISDN required more ICU admissions than the other patients (54.1 vs 33.3%, p = 0.02). Nevertheless 180-day hospital readmission was lower for patients who were receiving ISDN (8.1 vs 22.8%, p = 0.04). ISDN did not influence other clinical outcomes tested. Conclusion ISDN may minimize or prevent the consequences of altered haemodynamics. Lower rehospitalization rate with ISDN was seen in this study.