Inotuzumab ozogamicin in pediatric patients with relapsed/refractory acute lymphoblastic leukemia

Although inotuzumab ozogamicin (InO) is recognized as an effective agent in relapsed acute lymphoblastic leukemia (ALL) in adults, data on safety and efficacy in pediatric patients are scarce. We report the use of InO in 51 children with relapsed/ refractory ALL treated in the compassionate use program. In this heavily pretreated cohort, complete remission was achieved in 67% of patients with overt marrow disease. The majority (71%) of responders were negative for minimal residual disease. Responses were observed irrespective of cytogenetic subtype or number or type of prior treatment regimens. InO was welltolerated; grade 3 hepatic transaminitis or hyperbilirubinemia were noted in 6 (12%) and grade 3/4 infections in 11 (22%) patients. No patient developed sinusoidal obstruction syndrome (SOS) during InO therapy; however, 11 of 21 (52%) patients who underwent hematopoietic stem cell transplantation (HSCT) following InO developed SOS. Downregulation of surface CD22 was detected as a possible escape mechanism in three patients who developed a subsequent relapse after InO. We conclude that InO is a well-tolerated, effective therapy for children with relapsed ALL and prospective studies are warranted. Identification of risk factors for developing post-HSCT SOS and strategies to mitigate this risk are ongoing

Pitfalls of Hemodynamic Monitoring in Patients with Trauma

This article provides an update for the anesthesiology community on the mechanisms and limitations of common modalities used to assess the early hemodynamic status in patients with trauma. Figures are provided to illustrate important concepts through the use of computer simulation and real-world examples. This article is of value to anesthesiologists whose practice includes management of hemorrhagic shock

PT-SAFE: a software tool for development and annunciation of medical audible alarms

Recent reports by The Joint Commission as well as the Anesthesia Patient Safety Foundation have indicated that medical audible alarm effectiveness needs to be improved. Several recent studies have explored various approaches to improving the audible alarms, motivating the authors to develop real-time software capable of comparing such alarms. We sought to devise software that would allow for the development of a variety of audible alarm designs that could also integrate into existing operating room equipment configurations. The software is meant to be used as a tool for alarm researchers to quickly evaluate novel alarm designs. A software tool was developed for the purpose of creating and annunciating audible alarms. The alarms consisted of annunciators that were mapped to vital sign data received from a patient monitor. An object-oriented approach to software design was used to create a tool that is flexible and modular at run-time, can annunciate wave-files from disk, and can be programmed with MATLAB by the user to create custom alarm algorithms. The software was tested in a simulated operating room to measure technical performance and to validate the time-to-annunciation against existing equipment alarms. The software tool showed efficacy in a simulated operating room environment by providing alarm annunciation in response to physiologic and ventilator signals generated by a human patient simulator, on average 6.2 seconds faster than existing equipment alarms. Performance analysis showed that the software was capable of supporting up to 15 audible alarms on a mid-grade laptop computer before audio dropouts occurred. These results suggest that this software tool provides a foundation for rapidly staging multiple audible alarm sets from the laboratory to a simulation environment for the purpose of evaluating novel alarm designs, thus producing valuable findings for medical audible alarm standardization

Influence of auditory stimulation rates on evoked potentials during general anesthesia: relation between the transient auditory middle-latency response and the 40-Hz auditory steady state response

The auditory middle-latency response (transient) and the 40-Hz auditory steady state response (ASSR) are modulated by anesthetics. However, the quantitative relation between these evoked responses is difficult to obtain because of technical limitations of the recording methods used to obtain transients at high stimulation rates. This study uses continuous-loop averaging deconvolution to fill this technical gap and to study the relation between the transient and ASSR waveform during general anesthesia. The authors recorded 5- and 40-Hz transients and 40-Hz ASSRs in 13 subjects during general anesthesia. The 5- and 40-Hz transients were used to predict the 40-Hz ASSR by linearly superimposing the transient waveforms. The predicted and recorded ASSRs were analyzed and compared using phasor and Hotelling T(2) analyses. Grand-averaged recordings revealed differences in the early middle-latency peaks between 5- and 40-Hz transients, e.g., the peak P(x) was present only in 5-Hz transient. Only the predicted 40-Hz ASSR derived from the 40-Hz transient matched the actual ASSR. Phasor analysis showed that the early peaks contribute significantly to the steady state waveform, and this explains why 5-Hz transient does not predict the 40-Hz ASSR. Oscillations in both the 5- and 40-Hz transients were observed during anesthesia. The 40-Hz ASSR represents a composite waveform and arises when transient waveforms elicited with a 40-Hz stimulation rate are overlapped and superimposed. During general anesthesia, the morphology of the transient is dependent on the rate of stimulus presentation. The composite nature of the ASSR may explain nonmonotonic anesthetic dose-response relations observed by others

Can variable practice habits and injection port dead-volume put patients at risk?

Injection ports used to administer medications and draw blood samples have inherent dead-volume. This volume can potentially lead to inadvertent drug administration, contribute to erroneous laboratory values by dilution of blood samples, and increase the risk of vascular air embolism. We sought to characterize provider practice in management of intravenous (IV) and arterial lines and measure dead-volumes of various injection ports. A survey was circulated to anesthesiology physicians and nurses to determine practice habits when administering medications and drawing blood samples. Dead-volume of one and four-way injection ports was determined by injecting methylene blue to simulate medication administration or blood sample aspiration and using absorption spectroscopy to measure sample concentration. Among the 65 survey respondents, most (64.52%) increase mainstream flow rate to flush medication given by a 1-way injection port. When using 4-way stopcocks, 56.45% flush through the same injection site. To obtain a sample from an arterial line, 67.74% draw back blood and collect the sample from the same 4-way stopcock; 32.26% use a different stopcock. Mean (SD) dead-volume in microliters ranged from 0.1 (0.0) to 5.6 (1.0) in 1-way injection ports and from 54.1 (2.8) to 126.5 (8.3) in 4-way injection ports. The practices of our providers when giving medications and drawing blood samples are variable. The dead-volume associated with injection ports used at our institution may be clinically significant, increasing errors in medication delivery and laboratory analysis

Intraoperative Noise Increases Perceived Task Load and Fatigue in Anesthesiology Residents: A Simulation-Based Study

Operating rooms are identified as being one of the noisiest of clinical environments, and intraoperative noise is associated with adverse effects on staff and patient safety. Simulation-based experiments would offer controllable and safe venues for investigating this noise problem. However, realistic simulation of the clinical auditory environment is rare in current simulators. Therefore, we retrofitted our operating room simulator to be able to produce immersive auditory simulations with the use of typical sound sources encountered during surgeries. Then, we tested the hypothesis that anesthesia residents would perceive greater task load and fatigue while being given simulated lunch breaks in noisy environments rather than in quiet ones. As a secondary objective, we proposed and tested the plausibility of a novel psychometric instrument for the assessment of stress. In this simulation-based, randomized, repeated-measures, crossover study, 2 validated psychometric survey instruments, the NASA Task Load Index (NASA-TLX), composed of 6 items, and the Swedish Occupational Fatigue Inventory (SOFI), composed of 5 items, were used to assess perceived task load and fatigue, respectively, in first-year anesthesia residents. Residents completed the psychometric instruments after being given lunch breaks in quiet and noisy intraoperative environments (soundscapes). The effects of soundscape grouping on the psychometric instruments and their comprising items were analyzed with a split-plot analysis. A model for a new psychometric instrument for measuring stress that combines the NASA-TLX and SOFI instruments was proposed, and a factor analysis was performed on the collected data to determine the model's plausibility. Twenty residents participated in this study. Multivariate analysis of variance showed an effect of soundscape grouping on the combined NASA-TLX and SOFI instrument items (P = 0.003) and the comparisons of univariate item reached significance for the NASA Temporal Demand item (P = 0.0004) and the SOFI Lack of Energy item (P = 0.001). Factor analysis extracted 4 factors, which were assigned the following construct names for model development: Psychological Task Load, Psychological Fatigue, Acute Physical Load, and Performance-Chronic Physical Load. Six of the 7 fit tests used in the partial confirmatory factor analysis were positive when we fitted the data to the proposed model, suggesting that further validation is warranted. This study provides evidence that noise during surgery can increase feelings of stress, as measured by perceived task load and fatigue levels, in anesthesiologists and adds to the growing literature pointing to an overall adverse impact of clinical noise on caregivers and patient safety. The psychometric model proposed in this study for assessing perceived stress is plausible based on factor analysis and will be useful for characterizing the impact of the clinical environment on subject stress levels in future investigations

The use of pressure-tuning spectroscopy to distinguish between one- and two-electron transfer processes

The first use of pressure-tuning spectroscopy as a diagnostic tool in the evaluation of an intervalence transition band to determine the number of electrons transferred is described. The trinuclear complex [(CN) 5FeCNPt(NH 3) 4NCFe(CN) 5] 4− was subjected in solution to hydrostatic pressures from ambient to 1.5 kbar giving a Δ V * = −5.7 ± 0.2 cm 3 mol −1. Calculated values from various models ranged from −5.6 to −6.7 cm 3 mol −1 assuming a one-electron transfer event and a negligible innersphere reorganizational energy compared with the apparently very large outer-sphere rearrangements that must occur

Simultaneously extracted transient and steady-state evoked responses during general anesthesia: Variability of different rates

Unintended intraoperative awareness occurs in one to two individuals out of every one thousand treated with general anesthesia. Patients that experience intraoperative awareness have significant post-operative psychological sequelae. The ability to detect intraoperative awareness is currently suboptimal because the mechanism employed by anesthetic drugs to impair consciousness remains poorly understood. Studies have suggested that evoked potentials (EP) may be used to monitor the depth of anesthesia. Both transient and steady state responses can be simultaneously extracted using the Continuous Loop Averaging Deconvolution (CLAD) method with specially designed CLAD sequences. 20 Hz and 30 Hz jittered CLAD sequences in addition to 5 Hz isochronic and 40 Hz jittered CLAD sequences were applied in baseline awake and general anesthesia conditions. A qualitative method to assess the extracted EPs was developed in this study, termed Randomized Split Set Average (RSSA). The results showed that EPs extracted during general anesthesia require a greater number of sweeps to obtain a signal-to-noise ratio comparable to that observed in EPs extracted during the awake state. Therefore, the development of a real time or quasi real time EP monitoring system for anesthesia provides an increased challenge. The RSSA employed in this study is a useful method for assessing the signal quality of EP responses

Factors Affecting Acoustics and Speech Intelligibility in the Operating Room: Size Matters

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