Background Prolonged (val)ganciclovir [(V)GCV] exposure for ≥ 6 weeks is a known predisposing factor for cytomegalovirus (CMV) drug resistance. However, the selection of this threshold was based on limited data. Here, we sought to reappraise the risk factors for the development of (V)GCV resistance through a specific focus on kidney transplant recipients (KTRs). Methods This single-center retrospective study included 313 consecutive KTRs treated for a first CMV episode. Adjusted Cox multivariate regression analysis was used for identifying independent risk factors. Results Antiviral drug resistance was identified in 20 (6%) KTRs. A cumulative (V)GCV exposure for more than 6 weeks (regardless of the viral load) was not associated with antiviral drug resistance (hazard ratio [HR] = 2.45, 95% confidence interval [CI] = 0.33−18.30, p = 0.38). On the opposite, persistent CMV DNAemia requiring (V)GCV treatment for more than 8 weeks was the main independent risk factor for antiviral drug resistance (HR = 11.68, 95% CI = 2.62−52.01, p = 0.001). (V)GCV treatment for more than 8 weeks was given to 9% and 18% of patients who had persistent or recurrent CMV DNAemia, respectively. These scenarios were associated with the occurrence of drug resistance in 39% and 12% of cases, respectively. Conclusions Cumulative (V)GCV exposure ≥ 6 weeks regardless of the viral load is not associated with antiviral drug resistance. On the opposite, prolonged exposure to (V)GCV during CMV replication (with a cutoff  ³ 8 weeks) appears to be a key factor.

AbstractmTOR inhibitors exert a preventive effect on cytomegalovirus (CMV) disease in CMV seropositive (R+) kidney transplant recipients, but their impact during the curative treatment of CMV disease in high‐risk kidney transplant recipients has not been investigated. We aimed to evaluate the efficacy and tolerance of mTOR inhibitors compared with mycophenolic acid in 63 consecutive kidney transplant recipients (80% of D+R−) suffering from CMV disease with a persistent or a recurrent CMV DNAemia. In this monocentric retrospective study, 16 had their treatment converted to mTOR inhibitors and 47 did not. The Kaplan–Meier curves did not show any significant differences in CMV DNAemia eradication (77% vs. 88% respectively; hazard ratio (HR), 1.648 [95% confidence interval (CI), 0.913–2.973]; log‐rank test, P = .132), DNAemia recurrence (36% vs. 47%; HR, 1.517 [95% CI, 0.574–4.007]; log‐rank test, P = .448) and CMV clinical recurrence (17% vs. 27%; HR, 1.375 [95% CI, 0.340–5.552]; log‐rank test, P = .677) between patients who received mTOR inhibitors and those who did not. These results were confirmed in uni‐ and multivariate time‐dependent Cox regressions. In summary, conversion from mycophenolic acid to mTOR inhibitors seems inadequate for improving CMV clearance or in better preventing CMV recurrences during severe or persistent CMV disease.

Background In France, physician-assisted suicide or euthanasia are not legal but are still debated. French intensive care unit (ICU) health care workers (HCWs) have an insider’s perspective on the global quality of the patient’s end-of-life, whether it occurs in ICU or not. However, their opinion about euthanasia/physician-assisted suicide remains unknown. The aim of this study is to investigate the opinion of French ICU HCWs about physician-assisted suicide/euthanasia. Results A total of 1149 ICU HCWs participated to a self-administered anonymous questionnaire: 411 (35.8%) physicians and 738 (64.2%) non-physicians. Among them, 76.5% indicated they were in favor of legalizing euthanasia/physician-assisted suicide. Non-physicians HCWs were significantly more in favor of the legalization of euthanasia/physician assisted suicide than physicians (87% vs 57.8% p < 0.001). Euthanasia/physician-assisted suicide of an ICU patient raised the most important difference in positive judgment between physicians and non-physicians HCWs (80.3% vs 42.2%; p < 0.001 of non-physicians and physicians, respectively). The questionnaire included three case vignettes of concrete examples which participated to the increase in the rate of response in favor of euthanasia/physician-assisted suicide legalization (76.5–82.9%; p < 0.001). Conclusions Keeping in mind the unknown representation of our sample, ICU HCWs, particularly non physicians, would be in favor of a law legalizing euthanasia/physician-assisted suicide.

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