Nilotinib after imatinib first-line: a real-life longitudinal cohort of patients with chronic myeloid leukaemia in chronic phase.

This prospective, observational study enrolled 150 adult patients with chronic myeloid leukaemia (CML) in chronic phase (CP) treated with nilotinib as second-line after imatinib, in a real life setting in France. Two-thirds of patients switched to nilotinib treatment due to lack of imatinib efficacy. Of 146 evaluable patients, 16 (11·0%) (95% confidence interval: 6·4-17·2%) achieved uMR4 , defined as undetectable molecular disease in cDNA with MR4 sensitivity (≥10 000 ABL1 transcripts) at 18 months and confirmed at 24 months (primary endpoint). Among patients without major molecular response (MMR) or deep molecular response (DMR) at study entry, 66·3% achieved MMR and 44·2% DMR within a median of 5·7 and 6·24 months, respectively. Fifty-three patients (36·3%) have prematurely terminated the study before 24 months of follow-up, primarily due to nilotinib treatment discontinuation (n = 43; 29·5%), mainly motivated by treatment intolerance (n = 27; 18·5%) and inefficacy (n = 10; 6·8%). The most frequent extra-haematological adverse events (AEs) reported as related to treatment with nilotinib were pruritus (16·4%), asthenia (13·7%) and dry skin (13·0%). Ischaemic cardiovascular AEs were reported in 18 patients (12·3%). This French nationwide large cohort adds valuable information to the body of evidence on the efficiency and safety of nilotinib in the treatment of patients with CP-CML.

Colonization and infection with extended-spectrum ß-lactamase-producing Enterobacteriaceae in ICU patients: what impact on outcomes and carbapenem exposure?

OBJECTIVES: It remains uncertain whether colonization and infection with ESBL-producing Enterobacteriaceae (ESBL-PE) affect the outcomes for ICU patients. Our objectives were to measure the effects of ESBL-PE carriage and infection on mortality, ICU length of stay (LOS) and carbapenem exposure in this population. METHODS: A cause-specific hazard model based on prospectively collected data was built to assess the impact of ESBL-PE colonization and infection on competing risks of death and ICU discharge at day 28 in a multicentre cohort of ICU patients. Carbapenem exposure during the ICU stay was compared between infected carriers, uninfected carriers and non-carriers. RESULTS: Among the 16,734 included patients, 594 (3.5%) were ESBL-PE carriers, including 98 (16.4%) with one or more ESBL-PE infections during the ICU stay. After adjustment for baseline and time-dependent confounders, ESBL-PE infections increased the probability of death at day 28 [adjusted cause-specific hazard ratio (aCSHR), 1.825, 95% CI 1.235-2.699, P = 0.0026] and the ICU LOS (aCSHR for discharge alive at day 28, 0.563, 95% CI 0.432-0.733, P < 0.0001). ESBL-PE carriage without infection extended the LOS (aCSHR, 0.623, 95% CI, 0.553-0.702, P < 0.0001), without affecting mortality (aCSHR, 0.906, 95% CI, 0.722-1.136, P = 0.3916). Carbapenem exposure increased in both infected and uninfected carriers when compared with non-carriers (627, 241 and 69 carbapenem days per 1000 patient days, respectively, P < 0.001). CONCLUSIONS: ESBL-PE infections increased carbapenem consumption, LOS and day 28 mortality. ESBL-PE infections were rather infrequent in carriers; however, even ESBL-PE carriage without infection increased carbapenem exposure and delayed discharge, thereby amplifying the selective pressure and the colonization pressure in the ICU.

Treatment intensity and outcome of nonagenarians selected for admission in ICUs: a multicenter study of the Outcomerea Research Group.

BACKGROUND: Outcome of very elderly patients admitted in intensive care unit (ICU) was most often reported for octogenarians. ICU admission demands for nonagenarians are increasing. The primary objective was to compare outcome and intensity of treatment of octogenarians and nonagenarians. METHODS: We performed an observational study in 12 ICUs of the Outcomerea™ network which prospectively upload data into the Outcomerea™ database. Patients >90 years old (case patients) were matched with patients 80-90 years old (control patients). Matching criteria were severity of illness at admission, center, and year of admission. RESULTS: A total of 2419 patients aged 80 or older and admitted from September 1997 to September 2013 were included. Among them, 179 (7.9 %) were >90 years old. Matching was performed for 176 nonagenarian patients. Compared with control patients, case patients were more often hospitalized for unscheduled surgery [54 (30.7 %) vs. 42 (23.9 %), p < 0.01] and had less often arterial monitoring for blood pressure [37 (21 %) vs. 53 (30.1 %), p = 0.04] and renal replacement therapy [5 (2.8 %) vs. 14 (8 %), p = 0.05] than control patients. ICU [44 (25 %) vs. 36 (20.5 %), p = 0.28] or hospital mortality [70 (39.8 %) vs. 64 (36.4 %), p = 0.46] and limitation of life-sustaining therapies were not significantly different in case versus control patients, respectively. Only 16/176 (14 %) of case patients were transferred to a geriatric unit. CONCLUSION: This multicenter study reported that nonagenarians represented a small fraction of ICU patients. When admitted, these highly selected patients received similar life-sustaining treatments, except RRT, than octogenarians. ICU and hospital mortality were similar between the two groups.