Dose-modified gemcitabine plus nab-paclitaxel front-line in advanced pancreatic ductal adenocarcinoma with baseline hyperbilirubinemia.

BACKGROUND: Von Hoff et al. demonstrated survival improvement with gemcitabine (GEM) + nab-paclitaxel (NabP) for metastatic pancreatic ductal adenocarcinoma (PDAC) compared to GEM alone. GEM + NabP resulted in a median overall survival (OS) and progression-free survival (PFS) of 8.5 and 5.5 months, respectively. Patients with baseline hyperbilirubinemia were excluded. Primary objective was OS. Secondary objectives included time on treatment (TOT), disease control rate, dosing practices, delays/admissions, and adverse effects. METHODS: Patients with borderline resectable, locally advanced, or metastatic PDAC who initiated front-line GEM-NabP during July 01, 2013-July 01, 2017 were reviewed. Patients with a baseline total bilirubin ≥2 mg/dL were included. RESULTS: Twelve patients total were included. Median age was 71 years old. Median baseline total bilirubin was 2.4 mg/dL (range, 2.1-5.2 mg/dL). 58% had metastatic disease. Median doses were NabP 100 mg/m2 + GEM 600 mg/m2 IV with a fixed-dose rate infusion (10 mg/m2/min). GEM-NabP was given biweekly or 3 weeks on 1 week off. Median OS, TOT, and disease control rate were 13.9, 5.2 months, and 58%, respectively. Fifty percent of patients required a dose delay. Metastatic patients only (n=7) had median OS and TOT of 6.9 and 2.1 months, respectively. No admissions related to toxicity were found. CONCLUSIONS: Our analysis revealed safety with NabP (median dose =100 mg/m2) + GEM (median dose =600 mg/m2 at fixed-dose rate) given predominately biweekly in patients with a baseline elevated total bilirubin (≥2 mg/dL).

Virtually Nursing: Emerging Technologies in Nursing Education.

Augmented reality and virtual simulation technologies in nursing education are burgeoning. Preliminary evidence suggests that these innovative pedagogical approaches are effective. The aim of this article is to present 6 newly emerged products and systems that may improve nursing education. Technologies may present opportunities to improve teaching efforts, better engage students, and transform nursing education.

Enhancing medical device training with hybrid physical-virtual simulators: smart peripherals for virtual devices.

We introduce a novel platform for medical device training: hybrid physical-virtual simulators of medical devices, combining touchscreen-enabled virtual emulations of real devices with sensorized physical peripherals to enable tactile, hands-on interaction between the trainee, simulated device and standardized patients or mannequins. The system enables objective measurement and recording of trainee performance, including interactions with both the virtual device elements and the physical components, and can include metrics and feedback not available in the real device. The system also includes an integrated wireless signaling device for use with standardized patients. We present the implementation of an example system, a virtual defibrillator with sensorized paddles and wireless signaling of successful defibrillator operation.

PleurAlert: an augmented chest drainage system with electronic sensing, automated alerts and internet connectivity.

We have enhanced a common medical device, the chest tube drainage container, with electronic sensing of fluid volume, automated detection of critical alarm conditions and the ability to automatically send alert text messages to a nurse's cell phone. The PleurAlert system provides a simple touch-screen interface and can graphically display chest tube output over time. Our design augments a device whose basic function dates back 50 years by adding technology to automate and optimize a monitoring process that can be time consuming and inconvenient for nurses. The system may also enhance detection of emergency conditions and speed response time.

A novel automated drug simulant recognition system for naturalistic real-time medical simulation.

The ability for a medical simulator to automatically recognize and respond to a "drug" injected during a training exercise offers powerful capabilities for objective assessment and real-time interaction. To address some of the limitations of available mannequin drug recognition systems, we developed a novel sensing system that recognizes an IV-injected agent based on an inherent property of the fluid. Our system uses varying concentrations of saline to represent different drugs and identification is made via conductivity measurement. The system also determines the volume administered and the time over which the dose is injected. Simulant solutions in IV bags (e.g., simulated Hextend or crystalloids) can be identified even if the bag is placed at a distance from the body. The system may offer advantages for field training exercises, as no external components need to be attached to the syringe or IV bag.

BodyWindows: enhancing a mannequin with projective augmented reality for exploring anatomy, physiology and medical procedures.

Augmented reality offers the potential to radically extend and enhance the capabilities of physical medical simulators such as full-body mannequin trainers. We have developed a system that transforms the surface of a mannequin simulator into both a display screen and an input device. The BodyWindows system enables a user to open, size, and reposition multiple viewports onto the simulator body. We demonstrate a dynamic viewport that displays a beating heart. Similar viewports could be used to display real-time physiological responses to interventions the user applies to the mannequin, such as injection of a simulated drug. Viewport windows can be overlapping and show anatomy at different depths, creating the illusion of "cutting" multiple windows into the body to reveal structures at different depths from the surface. The developed low-cost interface employees an IR light pen and the Nintendo Wiimote. We also report experiments using the Microsoft Kinect computer vision sensor to provide a completely hand-gesture based interface.

Delayed song maturation and territorial aggression in a songbird.

Asymmetries in competitive ability can determine the outcome of social interactions in animals and are often expressed through differences in sexual traits. Competitive ability (resource holding potential, RHP), trait expression and ultimately reproductive success may vary with an individual's age or experience. In some species, reproductively mature males delay acquisition of some adult traits and thereby signal their young age. Theory on animal contests predicts that individuals assess the RHP of an opponent relative to their own, such that escalation is more common between evenly matched opponents. Here, we test predictions from this hypothesis that males respond to a territorial intruder based on their RHP relative to the intruder's RHP. We simulated white-crowned sparrows (Zonotrichia leucophrys) intruding into the territory of a recruit or return. Playback of a song repertoire simulating a young male (recruit) elicited a weaker response from established territory holders (return), but a stronger response from recruits. Playback of a single song type simulating an older male elicited the opposite responses. This indicates that males distinguished between simulated young and old intruders based on song, and responded differently depending on their own experience. Our study highlights the possibility that receiver as well as sender traits should be considered when interpreting animal interactions.

The tool positioning tutor: a target-pose tracking and display system for learning correct placement of a medical device.

Safe and successful performance of medical procedures often requires the correct manual positioning of a tool. For example, during endotracheal intubation a laryngoscope is used to open a passage in the airway through which a breathing tube is inserted. During training it can be challenging for an experienced practitioner to effectively communicate to a novice the correct placement and orientation of a tool. We have implemented a real-time tracking and position display system to enhance learning correct laryngoscope placement. The system displays a 3D model of the laryngoscope. A clinical teacher can correctly position the laryngoscope to open the airway of a full-body simulator, then set this tool pose as the target position. The system displays to the learner the fixed, target pose and a real-time display of the current, "live" laryngoscope position. Positional error metrics are displayed as color-coded visual cues to guide the user toward successful targeting of the reference position. This technique provides quantitative assessment of the degree to which a learner has matched a specified "expert" position with a tool, and is potentially applicable to a wide variety of tools and procedures.

Real-time "x-ray vision" for healthcare simulation: an interactive projective overlay system to enhance intubation training and other procedural training.

We have developed a prototype of a real-time, interactive projective overlay (IPO) system that creates augmented reality display of a medical procedure directly on the surface of a full-body mannequin human simulator. These images approximate the appearance of both anatomic structures and instrument activity occurring within the body. The key innovation of the current work is sensing the position and motion of an actual device (such as an endotracheal tube) inserted into the mannequin and using the sensed position to control projected video images portraying the internal appearance of the same devices and relevant anatomic structures. The images are projected in correct registration onto the surface of the simulated body. As an initial practical prototype to test this technique we have developed a system permitting real-time visualization of the intra-airway position of an endotracheal tube during simulated intubation training.

Toward a comprehensive hybrid physical-virtual reality simulator of peripheral anesthesia with ultrasound and neurostimulator guidance.

We are developing a simulator of peripheral nerve block utilizing a mixed-reality approach: the combination of a physical model, an MRI-derived virtual model, mechatronics and spatial tracking. Our design uses tangible (physical) interfaces to simulate surface anatomy, haptic feedback during needle insertion, mechatronic display of muscle twitch corresponding to the specific nerve stimulated, and visual and haptic feedback for the injection syringe. The twitch response is calculated incorporating the sensed output of a real neurostimulator. The virtual model is isomorphic with the physical model and is derived from segmented MRI data. This model provides the subsurface anatomy and, combined with electromagnetic tracking of a sham ultrasound probe and a standard nerve block needle, supports simulated ultrasound display and measurement of needle location and proximity to nerves and vessels. The needle tracking and virtual model also support objective performance metrics of needle targeting technique.

Twenty-one novel microsatellite DNA loci isolated from the Puget Sound white-crowned sparrow, Zonotrichia leucophrys pugetensis.

The white-crowned sparrow, Zonotrichia leucophrys, has served as a model species for studies of song and reproductive physiology. Here, we describe primers for 21 novel microsatellite loci isolated from the Puget Sound subspecies, Zonotrichia leucophrys pugetensis, which will be useful for parentage and population genetic analyses. Based on genotypes from seven to 22 adult birds from one population, the average number of alleles per locus was 10.9 (four to 21 alleles) and observed heterozygosity varied from 0.50 to 1.00. All loci also amplified products in at least one of three other passerine species tested.

Hypertrophic osteoarthropathy effectively treated with zoledronic acid.

Hypertrophic osteoarthropathy (HOA) is a syndrome characterized by digital clubbing, arthralgias, and tissue swelling and is frequently described in association with bronchogenic carcinoma. The associated pain can be disabling, and symptoms are often resistant to conventional analgesic medications. We present a patient with HOA of the lower extremities and wrists that developed after bronchogenic carcinoma. The pain and swelling completely resolved after a single administration of 4 mg of zoledronic acid. The proposed pathogenesis of HOA and the mechanisms by which bisphosphonates might alleviate symptoms are reviewed.

Post-transplant interleukin-2 in patients with low-grade lymphoid neoplasms previously treated with fludarabine is limited by hematologic toxicity.

Given the favorable immunologic effects of IL-2 post transplant, we conducted a feasibility study examining rIL-2 1.0x106 IU/m2/day (SQ) beginning on D+14 post-transplant and continuing for 90 days in 12 patients with low-grade lymphoproliferative disorders. Prior to high-dose chemotherapy and autologous peripheral blood stem cell transplantation (HDCT), 11 patients underwent cytoreduction with fludarabine and cyclophosphamide (Flu/Cy); 11 were in complete remission (CR) and one was in partial remission at the time of HDCT. All 12 patients were in CR 90 days post-HDCT. At a median follow-up of 30 (range 3-44) months, seven patients (58%) remain in remission, four are alive with disease, and one has died of disease progression, resulting in an overall survival of 92%. Kaplan-Meier estimates of progression-free survival (PFS) for the group demonstrate a median of 31 (range 3-43) months. Five patients required rIL-2 cessation at 8-58 days after starting the therapy due to hematologic toxicity. These results are comparable to those achieved in other published bone marrow and peripheral blood stem cell transplantion (PBSCT) series without the addition of rIL-2. Furthermore, rIL-2 using this schedule following fludarabine-based cytoreduction was associated with excessive hematologic toxicity.

Effect of a physician-directed educational campaign on performance of proper diabetic foot exams in an outpatient setting.

BACKGROUND: The established guidelines for a diabetes foot examination include assessing circulatory, skin, and neurological status to detect problems early and reduce the likelihood of amputation. Physician adherence to the guidelines for proper examination is less than optimal. OBJECTIVE: Our objective was to increase compliance with the performance of a proper foot examination through a predominantly physician-directed interventional campaign. METHODS: The study consisted of 3 parts: a retrospective chart review to estimate background compliance, an educational intervention, and prospective chart review at 3 and 6 months. A properly documented foot examination was defined as assessing at least 2 of the 3 necessary components. The educational intervention consisted of 2 lectures directed at resident physicians and a quality assurance announcement at a general internal medicine staff meeting. Clinic support staff were instructed to remove the shoes and socks of all diabetic patients when they were placed in exam rooms, and signs reminding diabetics were placed in each exam room. RESULTS: There was a significant increase in the performance of proper foot examination over the course of the study (baseline 14.0%, 3 months 58.0%, 6 months 62.1%; P <.001). Documentation of any component of a proper foot examination also increased substantially (32.6%, 67.3%, 72.5%; P <.001). Additionally, performance of each component of a proper exam increased dramatically during the study: neurological (13.5%, 35.8%, 38.5%; P <.001), skin (23.0%, 64.2%, 69.2%; P <.001), and vascular (14.0%, 51.2%, 50.5%; P <.001). CONCLUSIONS: Patients with diabetes are unlikely to have foot examinations in their primary medical care. A simple, low-cost educational intervention significantly improved the adherence to foot examination guidelines for patients with diabetes.

Magnetic resonance imaging findings in a case of cytarabine-induced myelopathy.

A 44-year-old white male with an isolated central nervous system relapse of acute lymphoblastic leukemia was treated with intrathecal cytarabine. He developed Staphylococcus epidermidis meningitis, which was treated successfully with intrathecal vancomycin. Four weeks after the initiation of intrathecal cytarabine, the patient developed progressive ascending paralysis to the upper cervical level. Initial magnetic resonance imaging of the brain and spine were normal, and cerebrospinal fluid evaluation showed no evidence of ongoing infection and clearance of lymphoblasts. Three weeks later, magnetic resonance imaging demonstrated marked edema and peripheral enhancement of the spinal cord, consistent with cytarabine toxicity.