Fixed-duration ibrutinib plus venetoclax for first-line treatment of CLL: primary analysis of the CAPTIVATE FD cohort.

CAPTIVATE (NCT02910583) is an international phase 2 study in patients aged ≤70 years with previously untreated chronic lymphocytic leukemia (CLL). Results from the cohort investigating fixed-duration (FD) treatment with ibrutinib plus venetoclax are reported. Patients received 3 cycles of ibrutinib lead-in then 12 cycles of ibrutinib plus venetoclax (oral ibrutinib [420 mg/d]; oral venetoclax [5-week ramp-up to 400 mg/d]). The primary endpoint was complete response (CR) rate. Hypothesis testing was performed for patients without del(17p) with prespecified analyses in all treated patients. Secondary endpoints included undetectable minimal residual disease (uMRD) rates, progression-free survival (PFS), overall survival (OS), and safety. Of the 159 patients enrolled and treated, 136 were without del(17p). The median time on study was 27.9 months, and 92% of patients completed all planned treatment. The primary endpoint was met, with a CR rate of 56% (95% confidence interval [CI], 48-64) in patients without del(17p), significantly higher than the prespecified 37% minimum rate (P < .0001). In the all-treated population, CR rate was 55% (95% CI, 48-63); best uMRD rates were 77% (peripheral blood [PB]) and 60% (bone marrow [BM]); 24-month PFS and OS rates were 95% and 98%, respectively. At baseline, 21% of patients were in the high tumor burden category for tumor lysis syndrome (TLS) risk; after ibrutinib lead-in, only 1% remained in this category. The most common grade ≥3 adverse events (AEs) were neutropenia (33%) and hypertension (6%). First-line ibrutinib plus venetoclax represents the first all-oral, once-daily, chemotherapy-free FD regimen for patients with CLL. FD ibrutinib plus venetoclax achieved deep, durable responses and promising PFS, including in patients with high-risk features.

Negative affective priming: Reliability and associations with depression symptoms in three samples.

The negative affective priming (NAP) task is a behavioral measure of inhibition of emotional stimuli. Previous studies using the NAP task have found that individuals with depression show reduced inhibition of negative stimuli, suggesting that inhibition biases may play a role in the etiology and maintenance of depression. However, the psychometric properties of the NAP task have not been evaluated or reported. In the present study, we report data on the association between NAP task performance and depression symptoms in three independent samples, and we evaluate the internal consistency and test-retest reliability of the NAP effect indices. The NAP effect for both negative and positive target words had poor internal consistency in all three samples, as well as poor 2-week (Study 2) and 6-month (Study 3) test-retest reliability. The internal consistency and test-retest reliability of response times (RT) for the individual trial types were moderate to high, as were the intercorrelations between trial types. This pattern of results indicates that overall RT is reliable but variance in RTs for the different trial types in the NAP task is indistinguishable from variance in overall RT. Depression symptom severity was not associated with the NAP effect for negative or positive target words in any of the samples, which could be due to the poor reliability of the NAP effect. Based on these findings, we do not recommend that researchers use the NAP task as a measure of individual differences in the inhibition of emotional stimuli.

"A Lot to Offer": Nurses as Educators for Medical Residents in an Academic Medical Center Intensive Care Unit.

INTRODUCTION: The role of fully trained interprofessional clinicians in educating residents has not been rigorously explored. The intensive care unit (ICU), where multiprofessional teamwork is essential to patient care, represents an ideal training environment in which to study this role. This study aimed to describe the practices, perceptions, and attitudes of ICU nurses regarding teaching medical residents and to identify potential targets to facilitate nurse teaching. METHODS: Using a concurrent mixed-methods approach, we administered surveys and focus groups to ICU nurses from September to November 2019 at a single, urban, tertiary, academic medical center. Survey data were analyzed with descriptive and comparative statistics. Focus group data were analyzed using the Framework method of content analysis. RESULTS: Of nurses surveyed, 75 of 96 (78%) responded. Nurses generally held positive attitudes about teaching residents, describing it as both important (52%, 36/69) and enjoyable (64%, 44/69). Nurses reported confidence in both clinical knowledge base (80%, 55/69) and teaching skills (71%, 49/69), but identified time, uncertainty about teaching topics, and trainee receptiveness as potential barriers. Ten nurses participated in focus groups. Qualitative analysis revealed three major themes: nurse-specific factors that impact teaching, the teaching environment, and facilitators of teaching. DISCUSSION: ICU nurses carry positive attitudes about teaching residents, particularly when facilitated by the attending, but this enthusiasm can be attenuated by the learning environment, unknown learner needs, and trainee attitudes. Identified facilitators of nurse teaching, including resident presence at the bedside and structured opportunities for teaching, represent potential targets for interventions to promote interprofessional teaching.

Effect of seat height on manual wheelchair foot propulsion, a repeated-measures crossover study: part 2 - wheeling backward on a soft surface.

PURPOSE: The aim of this study was to test the hypotheses that, during manual-wheelchair foot propulsion backward on a soft surface, lowering the seat height increases speed, push frequency and push effectiveness, and decreases perceived difficulty. MATERIALS AND METHODS: In a repeated-measures crossover study, 50 able-bodied participants used one foot to propel a manual wheelchair 5 m backward on a soft surface at 5 seat heights, ranging from 5.08 cm below to about 5.08 cm above lower-leg length, in random order. We recorded Wheelchair Skills Test (WST) capacity scores and used the Wheelchair Propulsion Test (WPT) to calculate speed (m/s), push frequency (cycles/s) and push effectiveness (m/cycle). We also recorded the participants' perceived difficulty (0-4) and video-recorded each trial. RESULTS: WST capacity scores were reduced at the higher seat heights. Using repeated-measures models (adjusted for age, sex and order), there were negative relationships between seat height and speed (p < 0.0001) and push effectiveness (p < 0.0001). Lowering the seat height by 5.08 cm below lower-leg length corresponded to improvements in speed of 0.097 m/s and in push effectiveness of 0.101 m/cycle. The trend for push frequency was also significant (p = 0.035) but the effect size was smaller. Perceived difficulty increased with seat height (p < 0.0001). The video-recordings provided qualitative kinematic data regarding the seated "gait cycles". CONCLUSIONS: During manual-wheelchair foot propulsion backward on a soft surface, lowering the seat height increases speed and push effectiveness, and decreases perceived difficulty.IMPLICATIONS FOR REHABILITATIONBackward wheelchair foot propulsion on soft surfaces is affected by seat height.Speed (m/s) is improved if the seat height is lowered.Push effectiveness (m/gait cycle) is improved if the seat height is lowered.Perceived difficulty of propulsion is lower if the seat height is lowered.

Effect of seat height on manual wheelchair foot propulsion, a repeated-measures crossover study: part 1 - wheeling forward on a smooth level surface.

PURPOSE: To test the hypotheses that, during manual wheelchair foot propulsion forward on smooth level surfaces, lowering the seat height increases speed, push frequency and push effectiveness, and decreases perceived difficulty. MATERIALS AND METHODS: In a repeated-measures crossover study, 50 able-bodied participants used one foot to propel a manual wheelchair 10 m on a smooth level surface at 5 seat heights in random order, ranging from 5.08 cm below to about 5.08 cm above lower-leg length. We recorded Wheelchair Skills Test (WST) capacity scores and used the Wheelchair Propulsion Test (WPT) to calculate speed (m/s), push frequency (cycles/s) and push effectiveness (m/cycle). We also recorded the participants' perceived difficulty (0-4) and video-recorded each trial. RESULTS: WST capacity scores were reduced at the higher seat heights. Using repeated-measures models (adjusted for age, sex and order), there were negative relationships between seat height and speed (p < 0.0001) and push effectiveness (p < 0.0001). Lowering the seat height by 5.08 cm below lower-leg length corresponded to improvements in speed of 0.20 m/s and in push effectiveness of 0.20 m/cycle. The trend for push frequency was also significant (p = 0.003) but the effect size was smaller. Perceived difficulty increased with seat height (p < 0.001). The video-recordings provided qualitative kinematic data regarding the seated "gait cycles". CONCLUSIONS: During manual wheelchair foot propulsion forward on smooth level surfaces, lowering the seat height increases speed and push effectiveness, and decreases perceived difficulty. CLINICAL TRIAL REGISTRATION NUMBER: NCT03330912.Implications for RehabilitationGenerally, wheelchairs used for forward foot propulsion should have a seat height that is 2.54-5.08 cm less than the sitting lower-leg length.Clinicians should, however, take into consideration other functions that may be adversely affected by lowering the seat height.

Development, Implementation, and Impact of a Proning Team During the COVID-19 Intensive Care Unit Surge.

BACKGROUND: Prone positioning has been used as an intervention to improve oxygenation in critically ill patients with acute respiratory distress syndrome. During the COVID-19 pandemic, resources were even more limited given a surge in acute respiratory distress syndrome patients, which outstripped intensive care unit (ICU) capacity at many institutions. LOCAL PROBLEM: The purpose of this article is to describe the development and implementation of a proning team during the surge in ICU patients with COVID-19 and to measure the impact of the program through surveys of staff involved. METHODS/INTERVENTIONS: A proning protocol and educational plan was developed. A proning team of redeployed staff was created. A survey of ICU registered nurses and proning team members was used to evaluate the benefits and challenges of the proning team. RESULTS: The proning team was successful in safely performing more than 300 proning and supinating maneuvers for critically ill patients. There is overwhelming support within the institution for a proning team for future COVID-19 surges. DISCUSSION: The development and implementation of the proning team happened quickly to assist with the surge of patients and off-load work from ICU registered nurses. Despite the success of the proning team, more clearly defined roles and expectations, as well as additional education, are needed to further enhance teamwork and workflow. CONCLUSIONS: Creation of the proning team was a creative use of resources that helped manage the large and medically complex patient population. This work may serve as a guide to other health care institutions.

Decreased brain docosahexaenoic acid content produces neurobiological effects associated with depression: Interactions with reproductive status in female rats.

Decreased tissue levels of docosahexaenoic acid (DHA; 22:6n-3) are implicated in the etiologies of non-puerperal and postpartum depression. With the aim of determining neurobiological sequelae of decreased brain DHA content, this study examined the effects of a loss of brain DHA content and concurrent reproductive status in adult female Long-Evans rats. An alpha-linolenic acid-deficient diet and breeding protocols were used to produce virgin and parous female rats with cortical phospholipid DHA levels 23-26% lower than virgin and parous rats fed a control diet containing adequate alpha-linolenic acid. Parous dams were tested/euthanized at weaning (postnatal day 20) of the second litter; virgin females, during diestrus. Decreased brain DHA was associated with decreased hippocampal BDNF gene expression and increased relative corticosterone response to an intense stressor, regardless of reproductive status. In virgin females with decreased brain DHA, serotonin content and turnover in frontal cortex were decreased compared to virgin females with normal brain DHA. In parous dams with decreased brain DHA, the density of 5-HT(1A) receptors in the hippocampus was increased, corticosterone response to an intense stressor was increased, and the latency to immobility in the forced swim test was decreased compared to parous dams with normal DHA. These findings demonstrate neurobiological alterations attributable to decreased brain DHA or an interaction of parous status and brain DHA level. Furthermore, the data are consistent with findings in depressed humans, and thus support a role for DHA as a factor in the etiologies of depressive illnesses, particularly postpartum depression.

Standard work for room entry: Linking lean, hand hygiene, and patient-centeredness.

BACKGROUND: Healthcare-associated infections are costly and fatal. Substantial front-line, administrative, regulatory, and research efforts have focused on improving hand hygiene. PROBLEM: While broad agreement exists that hand hygiene is the most important single approach to infection prevention, compliance with hand hygiene is typically only about 40%(1). GOALS: Our aim was to develop a standard process for room entry in the intensive care unit that improved compliance with hand hygiene and allowed for maximum efficiency. STRATEGY: We recognized that hand hygiene is a single step in a substantially more complicated process of room entry. We applied Lean engineering techniques to develop a standard process that included both physical steps and also standard communication elements from provider to patients and families and created a physical environment to support this. RESULTS: We observed meaningful improvement in the performance of the new standard as well as time savings for clinical providers with each room entry. We also observed an increase in room entries that included verbal communication and an explanation of what the clinician was entering the room to do. IMPLICATIONS: The design and implementation of a standardized room entry process and the creation of an environment that supports that new process has resulted in measurable positive outcomes on the medical intensive care unit, including quality, patient experience, efficiency, and staff satisfaction. Designing a process, rather than viewing tasks that need to happen in close proximity in time (either serially or in parallel) as unrelated, simplifies work for staff and results in higher compliance to individual tasks.

Low brain DHA content worsens sensorimotor outcomes after TBI and decreases TBI-induced Timp1 expression in juvenile rats.

The effects of dietary modulation of brain DHA content on outcomes after TBI were examined in a juvenile rat model. Long-Evans rats with normal or diet-induced decreases in brain DHA were subjected to a controlled cortical impact or sham surgery on postnatal day 17. Rats with the greatest decreases in brain DHA had the poorest sensorimotor outcomes after TBI. Ccl2, Gfap, and Mmp 9 mRNA levels, and MMP-2 and -9 enzymatic activities were increased after TBI regardless of brain DHA level. Lesion volume was not affected by brain DHA level. In contrast, TBI-induced Timp1 expression was lower in rats on the Deficient diet and correlated with brain DHA level. These data suggest that decreased brain DHA content contributes to poorer sensorimotor outcomes after TBI through a mechanism involving modulation of Timp1 expression.

Sensorimotor behavioral tests for use in a juvenile rat model of traumatic brain injury: assessment of sex differences.

Modeling juvenile traumatic brain injury (TBI) in rodents presents several unique challenges compared to adult TBI, one of which is selecting appropriate sensorimotor behavioral tasks that enable the assessment of the extent of injury and recovery over time in developing animals. To address this challenge, we performed a comparison of common sensorimotor tests in Long-Evans rats of various sizes and developmental stages (postnatal days 16-45, 35-190 g). Tests were compared and selected for their developmental appropriateness, scalability for growth, pre-training requirements, and throughput capability. Sex differences in response to TBI were also assessed. Grid walk, automated gait analysis, rotarod, beam walk, spontaneous forelimb elevation test, and measurement of motor activity using the force-plate actometer were evaluated. Grid walk, gait analysis, and rotarod failed to meet one or more of the evaluation criteria. Beam walk, spontaneous forelimb elevation test, and measurement of motor activity using the force-plate actometer satisfied all criteria and were capable of detecting motor abnormalities in rats subjected to controlled cortical impact on postnatal day 17. No sex differences were detected in the acute effects of TBI or functional recovery during the 28 days after injury using these tests. This demonstrates the utility of these tests for the evaluation of sensorimotor function in studies using rat models of pediatric TBI, and suggests that pre-pubertal males and females respond similarly to TBI with respect to sensorimotor outcomes.