Real-life experience with CPX-351 and impact on the outcome of high-risk AML patients: a multicentric French cohort.

CPX-351 is a liposomal formulation of cytarabine and daunorubicin approved for the treatment of adults with newly diagnosed, therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (MRC-AML). We retrospectively analyzed the efficacy and safety of CPX-351 in a real-world setting in 103 patients from 12 French centers, including the evaluation of molecular abnormalities at baseline and minimal residual disease (MRD) in responding patients, compared with a historical data set from Bordeaux-Toulouse DATAML registry. A favorable safety profile was observed, with a low frequency of alopecia (11%) and gastrointestinal toxicity (50%). The overall response rate after induction was 59%, and MRD <10-3 was achieved in 57% of complete response (CR)/CR with incomplete hematological recovery (CRi) patients. Only the presence of mutated TP53 (P = .02) or PTPN11 (P = .004) predicted lower response in multivariate analysis. Interestingly, high-risk molecular prognosis subgroups defined by 2017 European LeukemiaNet risk stratification, including ASXL1 and RUNX1 mutations, were not associated with a significantly lower response rate using CPX-351. With a median follow-up of 8.6 months, median overall survival (OS) was 16.1 months. Thirty-six patients underwent allogeneic stem cell transplantation with a significantly longer median OS compared with nontransplanted patients (P < .001). In multivariate analyses, only spliceosome mutations were associated with better OS (P = .04). In comparison with intensive chemotherapy, there was no difference in OS for patients <60 years. These data confirm the efficacy and safety of CPX-351 in high-risk AML (t-AML and MRC-AML) in a real-life setting. CPX-351 is a treatment of choice for patients aged ≥60 years.

BAM conditioning before autologous transplantation for lymphoma: a study on behalf of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC).

High-dose chemotherapy before autologous transplantation is a therapeutic option as consolidation in primary or relapsed lymphoma. Even if BEAM conditioning is generally used, alternative conditioning regimens have been published. The purpose of this study was to assess the outcome of 177 adult patients with lymphoma whose conditioning treatment included a BAM (busulfan, aracytine, and melphalan) regimen. With a median follow-up of 17.4 months, 2-year estimates of overall survival and progression-free survival for the entire group were 87% and 70.5%, respectively. Mucositis was the main reported complications and infectious episodes were described in 80.2% of patients. According to multivariate analysis, high performance status and age at diagnosis were adverse factors for survival and increased the risk of disease relapse and death. Despite its limitations, this retrospective study suggests that BAM combination is a valid conditioning regimen in lymphoma patients, with an acceptable rate of toxicity.

Effect of Bag-Mask Ventilation vs Endotracheal Intubation During Cardiopulmonary Resuscitation on Neurological Outcome After Out-of-Hospital Cardiorespiratory Arrest: A Randomized Clinical Trial.

Importance: Bag-mask ventilation (BMV) is a less complex technique than endotracheal intubation (ETI) for airway management during the advanced cardiac life support phase of cardiopulmonary resuscitation of patients with out-of-hospital cardiorespiratory arrest. It has been reported as superior in terms of survival. Objectives: To assess noninferiority of BMV vs ETI for advanced airway management with regard to survival with favorable neurological function at day 28. Design, Settings, and Participants: Multicenter randomized clinical trial comparing BMV with ETI in 2043 patients with out-of-hospital cardiorespiratory arrest in France and Belgium. Enrollment occurred from March 9, 2015, to January 2, 2017, and follow-up ended January 26, 2017. Intervention: Participants were randomized to initial airway management with BMV (n = 1020) or ETI (n = 1023). Main Outcomes and Measures: The primary outcome was favorable neurological outcome at 28 days defined as cerebral performance category 1 or 2. A noninferiority margin of 1% was chosen. Secondary end points included rate of survival to hospital admission, rate of survival at day 28, rate of return of spontaneous circulation, and ETI and BMV difficulty or failure. Results: Among 2043 patients who were randomized (mean age, 64.7 years; 665 women [32%]), 2040 (99.8%) completed the trial. In the intention-to-treat population, favorable functional survival at day 28 was 44 of 1018 patients (4.3%) in the BMV group and 43 of 1022 patients (4.2%) in the ETI group (difference, 0.11% [1-sided 97.5% CI, -1.64% to infinity]; P for noninferiority = .11). Survival to hospital admission (294/1018 [28.9%] in the BMV group vs 333/1022 [32.6%] in the ETI group; difference, -3.7% [95% CI, -7.7% to 0.3%]) and global survival at day 28 (55/1018 [5.4%] in the BMV group vs 54/1022 [5.3%] in the ETI group; difference, 0.1% [95% CI, -1.8% to 2.1%]) were not significantly different. Complications included difficult airway management (186/1027 [18.1%] in the BMV group vs 134/996 [13.4%] in the ETI group; difference, 4.7% [95% CI, 1.5% to 7.9%]; P = .004), failure (69/1028 [6.7%] in the BMV group vs 21/996 [2.1%] in the ETI group; difference, 4.6% [95% CI, 2.8% to 6.4%]; P < .001), and regurgitation of gastric content (156/1027 [15.2%] in the BMV group vs 75/999 [7.5%] in the ETI group; difference, 7.7% [95% CI, 4.9% to 10.4%]; P < .001). Conclusions and Relevance: Among patients with out-of-hospital cardiorespiratory arrest, the use of BMV compared with ETI failed to demonstrate noninferiority or inferiority for survival with favorable 28-day neurological function, an inconclusive result. A determination of equivalence or superiority between these techniques requires further research. Trial Registration: clinicaltrials.gov Identifier: NCT02327026.

Questionnaire of Memory (Q-MEM): A new measure of everyday memory functioning in school-age children.

We present a new measure of everyday memory, the Questionnaire of Memory (Q-MEM), which is specifically adapted for the ecological assessment of memory disorders in school-age children and constructed with four sections tapping effortful/intentional learning, automatic/procedural learning, prospective memory/organization, and working memory. Confirmatory Factor Analyses supported the Q-MEM's four-factor structure in 700 five-to twelve-year-old children. The analyses also revealed a good internal reliability and a good test-retest fidelity. Finally, comparisons between Q-MEM profiles of children with learning disabilities and typically developing children revealed significant differences. Therefore, the Q-MEM is a promising measure for identifying memory problems in children.

Performance characteristics of the Access AMH assay for the quantitative determination of anti-Müllerian hormone (AMH) levels on the Access* family of automated immunoassay systems.

OBJECTIVES: Anti-Müllerian hormone (AMH) measurement is useful as an aid in the evaluation of ovarian reserve. In the past, its conventional use was restricted by the low-throughput and variability of existing manual AMH assays. We developed the automated Access AMH assay for the quantitative determination of AMH levels on the Access family of immunoassay systems. The analytical performance of this new assay was evaluated. DESIGN AND METHODS: Sensitivity, dilution linearity, assay imprecision, AMH sample stability, lot-to-lot comparison and correlation with AMH Gen II assay (Beckman Coulter, Inc.) were evaluated. Reference intervals for Access AMH were established in healthy females, males, newborns (≤60days) and pediatric males classified by Tanner stages. RESULTS: The limit of blank and limit of detection were below 0.0077 and 0.0098ng/mL, respectively. The limit of quantitation was 0.010ng/mL. The total imprecision ranged from 2.4 to 5.2%. Linearity was observed up to 24ng/mL. Sample storage at room temperature up to 48h, at 2-8°C up to 7days and at -20°C up to 15months had no impact on measured AMH. The correlation study gave a coefficient between 0.99 and 1 and a regression slope between 0.89 and 0.92. Excellent lot-to-lot comparability was observed on controls and patient samples with a maximum bias of 3.7% between 2.81 and 15.03ng/mL. CONCLUSIONS: The fully automated Access AMH immunoassay demonstrates excellent analytical performance. As a consequence, the availability of this assay will represent a robust, fast and precise alternative to manual AMH assay testing.

Time's up! Involvement of metamemory knowledge, executive functions, and time monitoring in children's prospective memory performance.

This study examined time-based prospective memory (PM) in children and explored the possible involvement of metamemory knowledge and executive functions in the use of an appropriate time-monitoring strategy depending on the ongoing task's difficulty. Specifically, a sample of 72 typically developing children aged 4, 6, and 9 years old were given an original PM paradigm composed of both an ongoing procedural activity and a PM task. Half of the participants (expert group) were trained in the ongoing activity before the prospective test. As expected, results show that time monitoring had a positive effect on children's PM performance. Furthermore, mediation analyses reveal that strategic time monitoring was predicted by metamemory knowledge in the expert group but only by executive functions in the novice group. Overall, these findings provide interesting avenues to explain how metamemory knowledge, strategy use, and executive functions interact to improve PM performance during childhood.

Procedural learning, consolidation, and transfer of a new skill in Developmental Coordination Disorder.

The aim of this study was to explore the differences in procedural learning abilities between children with DCD and typically developing children by investigating the steps that lead to skill automatization (i.e., the stages of fast learning, consolidation, and slow learning). Transfer of the skill to a new situation was also assessed. We tested 34 children aged 6-12 years with and without DCD on a perceptuomotor adaptation task, a form of procedural learning that is thought to involve the cerebellum and the basal ganglia (regions whose impairment has been associated with DCD) but also other brain areas including frontal regions. The results showed similar rates of learning, consolidation, and transfer in DCD and control children. However, the DCD children's performance remained slower than that of controls throughout the procedural task and they reached a lower asymptotic performance level; the difficulties observed at the outset did not diminish with practice.

Age difference in dual-task interference effects on procedural learning in children.

The current study aimed to investigate the role played by explicit mechanisms during procedural learning in two age groups of children (7 and 10 years) using a dual-task paradigm. To do this, we explored the effect of an interference task during the early and late phases of a mirror tracing learning task. The results showed a differential impact of the secondary task on the two age groups, but only during the first learning phase; the performance of 10-year-olds was affected by the second task, whereas in 7-year-olds no performance difference was found between the single- and dual-task conditions. Overall, our study suggests that there are differences in the amount of effortful processing in which 7- and 10-year-olds engage at the beginning of the learning process; procedural learning in young children is mainly implicit, as attested by its lesser sensitivity to an interference task, whereas high-level explicit mechanisms seem to contribute to the procedural performance of 10-year-olds. However, these explicit mechanisms, even if they have an effect on performance, might not have an impact on the learning curve given that no difference in rate of acquisition was found between age groups. These findings are discussed in the light of classical conceptions of procedural learning.

The benefits of errorless learning for serial reaction time performance in Alzheimer's disease.

Identifying the conditions favoring new procedural skill learning in Alzheimer's disease (AD) could be important for patients' autonomy. It has been suggested that error elimination is beneficial during skill learning, but no study has explored the advantage of this method in sequential learning situations. In this study, we examined the acquisition of a 6-element perceptual-motor sequence by AD patients and healthy older adults (control group). We compared the impact of two preliminary sequence learning conditions (Errorless versus Errorful) on Serial Reaction Time performance at two different points in the learning process. A significant difference in reaction times for the learned sequence and a new sequence was observed in both conditions in healthy older participants; in AD patients, the difference was significant only in the errorless condition. The learning effect was greater in the errorless than the errorful condition in both groups. However, while the errorless advantage was found at two different times in the learning process in the AD group, in the control group this advantage was observed only at the halfway point. These results support the hypothesis that errorless learning allows for faster automation of a procedure than errorful learning in both AD and healthy older subjects.

Age-related differences in perceptuomotor procedural learning in children.

Procedural learning is generally considered to proceed in a series of phases, with cognitive resources playing an important role during the initial step. From a developmental perspective, little is known about the development of procedural learning or the role played by explicit cognitive processes during learning. The main objectives of this study were (a) to determine whether procedural learning performance improves with age by comparing groups of 7-year-old children, 10-year-old children, and adults and (b) to investigate the role played by executive functions during the acquisition in these three age groups. The 76 participants were assessed on a computerized adaptation of the mirror tracing paradigm. Results revealed that the youngest children had more difficulty in adapting to the task (they were slower and committed more errors at the beginning of the learning process) than 10-year-olds, but despite this age effect observed at the outset, all children improved performance across trials and transferred their skill to a different figure as well as adults. Correlational analyses showed that inhibition abilities play a key role in the performance of 10-year-olds and adults at the beginning of the learning but not in that of 7-year-olds. Overall, our results suggest that the age-related differences observed in our procedural learning task are at least partly due to the differential involvement of inhibition abilities, which may facilitate learning (so long as they are sufficiently developed) during the initial steps of the learning process; however, they would not be a necessary condition for skill learning to occur.

Intact procedural motor sequence learning in developmental coordination disorder.

The purpose of the present study was to explore the possibility of a procedural learning deficit among children with developmental coordination disorder (DCD). We tested 34 children aged 6-12 years with and without DCD using the serial reaction time task, in which the standard keyboard was replaced by a touch screen in order to minimize the impact of perceptuomotor coordination difficulties that characterize this disorder. The results showed that children with DCD succeed as well as control children at the procedural sequence learning task. These findings challenge the hypothesis that a procedural learning impairment underlies the difficulties of DCD children in acquiring and automatizing daily activities. We suggest that the previously reported impairment of children with DCD on the serial reaction time task is not due to a sequence learning deficit per se, but rather due to methodological factors such as the response mode used in these studies.

Procedural learning in specific language impairment: effects of sequence complexity.

According to the procedural deficit hypothesis (PDH), abnormal development in the procedural memory system could account for the language deficits observed in specific language impairment (SLI). Recent studies have supported this hypothesis by using a serial reaction time (SRT) task, during which a slower learning rate is observed in children with SLI compared to controls. Recently, we obtained contrasting results, demonstrating that children with SLI were able to learn a sequence as quickly and as accurately as controls. These discrepancies could be related to differences in the statistical structure of the SRT sequence between these studies. The aim of this study was to further assess, in a group of 21 children with SLI, the PDH with second-order conditional sequences, which are more difficult to learn than those used in previous studies. Our results show that children with SLI had impaired procedural memory, as evidenced by both longer reaction times and no sign of sequence-specific learning in comparison with typically developing controls. These results are consistent with the PDH proposed by Ullman and Pierpont (2005) and suggest that procedural sequence-learning in SLI children depends on the complexity of the to-be-learned sequence.