Injection Pad Research Articles

12481 Evaluating The Device Handling And Preference Assessment Questionnaire For Growth Hormone Deficiency: Results From Content Validation Interviews

Abstract Disclosure: J. Neergaard: Employee; Self; Novo Nordisk. S. Akhtar: Employee; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk. B. Berg: Employee; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk. S. Hamilton: Employee; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk. E. Hildebrand: Consulting Fee; Self; Novo Nordisk. J. Medina: Employee; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk. G. Ter-Borch: Employee; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk. N. Rasmussen: Employee; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk. Background: Patient experiences with injection devices may affect treatment adherence, and hence it is important to ensure patient-reported outcomes (PRO) instruments used to assess experience are supported by evidence of validity. As part of a study that compared patient preference and ease of use between the devices used to administer Somapacitan (Sogroya®, Novo Nordisk A/S) and Somatrogon (Ngenla®, Pfizer), we assessed relevance, comprehensiveness and comprehension of a PRO instrument, the Device Handling and Preference Assessment Questionnaire (DHPAQ), in adolescent patients with growth hormone deficiency (GHD) and their caregivers. Methods: We recruited 33 adolescent patients with GHD and 37 caregivers across five sites in the US for an open label, randomized, crossover study in which participants simulated an injection with each device using an injection pad or mannequin. The DHPAQ was used to assess patients’ device preference. Two-sided statistical tests with 5% significance levels were performed using DHPAQ responses. After completing the DHPAQ, a random subgroup of 10 adolescents and 10 caregivers were offered additional compensation to participate in a cognitive interview (CI). The CIs were conducted in accordance with the US Food and Drug Administration 2022 Principles for PRO Instruments and 2009 PRO Guidance for Industry. Trained interviewers used a structured guide to evaluate questions, statements, tasks and response options in the DHPAQ. Participants’ interview responses for each question were coded and added to summary tables. These summary tables were evaluated by the study team to determine the relevance, comprehensiveness and participant comprehension of instructions, item stems and response options. Results: When asked if any questions in the DHPAQ did not seem relevant to their device experience, all 20 CI participants answered “no”. Questions on “learning how to use the device”, “selecting the correct dose” and “injecting the dose” were ranked as most relevant. Participants responses from the CIs supported perceived comprehensiveness of all DHPAQ items. All CI participants reported comprehension of all test items in the DHPAQ, and only three items did not receive a “no difficulty” response from all 20 participants. In the main study, the number of participants who preferred the somapacitan device was significantly greater than those who preferred the somatrogon device (84.3% vs 12.9%, p<0.0001). More participants found the somapacitan device easy or very easy to use compared with the somatrogon device (98.6% vs 74.3%). Conclusions: The results from the CIs indicated that the instructions, item stems and response options of the DHPAQ were relevant, comprehensive and fully comprehended by all participants. In the main study, patients with GHD and their caregivers were found to prefer the somapacitan device to the somatrogon device. Presentation: 6/2/2024

Acceptability of CYLTEZO pen among biologics autoinjector patients, autoinjector Naïve patients, and healthcare professionals

ABSTRACT Background Cyltezo® (Adalimumab-adbm) is an FDA-approved interchangeable biosimilar for Humira® (adalimumab reference product [RP]) that helps treat chronic inflammatory conditions. Adalimumab-adbm is administered via an autoinjector, the adalimumab-adbm pen. This study assessed user opinions related to usability, perceptions, convenience, safety features, and acceptability of the adalimumab-adbm pen. Methods 98 Humira Pen users, 100 biologics pen naïve patients, and 99 health care professionals simulated use of the adalimumab-adbm pen on injection pads. Opinions were captured with a validated questionnaire using Likert-type scales during moderated interviews. Binomial tests were conducted for top-two ratings percentages. Results Nearly 90% of participants found the adalimumab-adbm pen ‘easy’ or ‘very easy’ to use, handle, and learn how to use. Almost 90% of volunteers thought the pen was ‘very’ or ‘extremely’ solid and convenient to use at home. Around 80% found the pen to be ‘very’ or ‘extremely’ comfortable. Over 90% of respondents said they would be ‘satisfied’ or ‘very satisfied’ with the safety features and the device itself. Nearly 90% of respondents indicated being ‘very’ or ‘extremely’ open to adopting the adalimumab-adbm pen. Conclusions The adalimumab-adbm pen provided users with a positive experience with features that benefit perceptions of usability, handling, safety, convenience, and acceptability.

The Concizumab Pen-Injector is Easy to Use and Preferred by Hemophilia Patients and Caregivers: A Usability Study Assessing Pen-Injector Handling and Preference.

Concizumab is a once-daily prophylactic treatment developed for patients with hemophilia A or B (HA/HB) with or without inhibitors. It is the first treatment for hemophilia patients to be delivered subcutaneously using a pre-filled, multi-dose pen-injector with a 4 mm, 32 G needle. To investigate patient and caregiver handling and preference for the concizumab pen-injector compared with current injection systems used to treat hemophilia. This preference and handling study was conducted in accordance with authority guidelines for approval of new devices and included adults and adolescents with HA/HB with or without inhibitors and caregivers currently administering factor replacement therapy or factor VIII mimetic (emicizumab) therapy. All participants underwent a training session, followed by a test session during which participants independently administered a single pen-injection into an injection pad or manikin. Time to train, time to prepare and inject, and number of complete independent injections handling the pen were assessed. Participants evaluated handling and preference via the Hemophilia Device Handling and Preference Assessment Questionnaire. 80 participants (44 adults, 21 adolescents, 15 caregivers) currently using factor replacement therapy (n=41, 51%) or emicizumab (n=39, 49%) participated. Average training time and time to complete an injection were 7 min 49s and 1 min 21s. In total, 98% of independent complete injections were achieved at first attempt. 98% (n=78; 95% confidence interval [CI] 91-100%) of participants assessed the pen-injector as either "easy" or "very easy" to use. 88% of participants preferred the pen-injector (n=70; 95% CI 78-94%) over their current injection system, and 9% (n=7) reported "no preference". Participants found the concizumab pen-injector easy to learn and easy to use and preferred it over their current injection systems.

Batch testing and noise rate optimization of MRPC3b for CBM-TOF/STAR-eTOF

The Compressed Baryonic Matter (CBM) experiment is one of the major scientific spectrometers of the future Facility for Antiproton and Ion Research (FAIR) in Darmstadt. As one of the core sub-systems in CBM experiment for charged hadron identification, the Time-of-Flight (TOF) system is required to have a time resolution better than 80 ps. According to the final state particle flux distribution, the CBM-TOF will be constructed with several types of Multi-gap Resistive Plate Chambers (MRPC). In the outer region of the TOF wall where the particle fluxes are around 1 kHz/cm2, MRPCs with ultra-thin float glass electrodes are considered as a cost effective solution. MRPC3b prototypes have been developed and tested with excellent performance which could meet all the requirements. Before the construction of CBM-TOF, approximately 80 MRPC3bs are assembled for the STAR endcap TOF (STAR-eTOF) upgrade at RHIC as part of the FAIR Phase-0 programs for CBM-TOF which provides a valuable opportunity for detector stability test under high flux environments. This paper will introduce the batch test of the MRPC3bs for STAR-eTOF upgrade. Time resolution of better than 70 ps and efficiency of around 95% are achieved. Notably, during the batch test, it has been observed that the noise rates of the two edge strips in each counter are significantly higher than those of the middle strips. Simulations with Computer Simulation Technology (CST) Studio Suite are carried out and several kinds of MRPC prototypes are designed and tested accordingly. Based on the simulation and test results, the design of the MRPC3b has been further optimized by modify the shape and position of High-Voltage injection pad and increasing the distance between the glass edge and both end strips, resulting in a significant suppression of noise rates in the edge strips.

Low-Cost Fishhook Removal Simulation.

The target audiences for this hands-on innovation are health care providers including medical students and emergency medicine residents. This simulation is also appropriate for small group sessions teaching the layperson. While generally not life-threating fishhook injuries are commonplace. They can end a day of recreation or an outdoor trip and possibly result in a visit to an emergency department or urgent care. Hands-on education on fishhook removal techniques that minimize tissue damage is rarely provided in wilderness first aid or traditional medical education. To the best of our knowledge, to date there are only two studies on fishhook removal simulations in medical and wilderness first aid education.1,2 The previously described simulation models are limited by accessibility of materials, realism, and cost. The goal of this small group session is to fill the gap in training on fishhook injuries. At the end of the session participants should be able to describe the parts of a fishhook, as well as demonstrate and have increased confidence in performing multiple fishhook removal techniques. Social learning theory is the conceptual framework for this small group session.3,4 This reflects the idea that students learn not only through repetition with trial and error, but through social interactions, observing and modeling successes of others. As a result, while this simulation requires a facilitator ensure the required items are available it does not necessitate a facilitator be present over the entire duration. Participants perform common fishhook removal techniques with hands-on skill development using commercially available silicone sponge injection pad trainers. Evaluating this small group session at a wilderness medicine training attended by medical and physician assistant students and their guests, self-reported confidence in fishhook removal before and after the simulation was assessed with a paired t-test. Survey results of perceived effectiveness and value of the simulation were also evaluated. The average confidence increased 58% after the simulation (p<0.005). The mean level of effectiveness was 87% and the participant perceived monetary value of the simulation materials was greater than actual cost. This innovation is a cost-friendly way to provide education and practice on fishhook removal. It requires minimal set up time and pre-learning can be easily modified to the expected knowledge and experience of participants. Understanding the fishhook removal techniques and increased levels of confidence has the potential to make participants more efficient when caring for patients. It may result in greater likelihood of success in removing fishhooks with minimal tissue damage. Fishhook injuries, medical simulation, emergency medical education, wilderness first aid, wound management, injection pad trainers.

Abstract 6800: Unique autologous cancer vaccine comprised of irradiated whole tumor cells and MBTA (rWTC-MBTA) triggers antitumor immune response to prevent metastasis

Abstract Despite the advances made in cancer treatment over the past decades, one statistic has remained unchanged: metastatic cancer accounts for 90 percent of annual cancer deaths in the United States. Our group previously demonstrated that an autologous whole tumor cell vaccine (rWTC-MBTA: irradiated autologous whole tumor cells pulsed with Mannan-BAM, TLR ligands, and anti-CD40 antibody) had a potent anti-tumor immune response and prolonged survival in a mouse colon carcinoma model. To investigate whether rWTC-MBTA would work in “cold” tumor models, we evaluated the vaccine’s effect on preventing and treating tumor metastasis in 4T1 breast tumors. Our data showed that vaccinated mice could significantly prevent lung metastasis in both intravenous injection and mammary pad subcutaneous implantation animal models. Further, we used another metastasis model that more closely mimics clinical practice by resecting the primary tumor after metastasis development. The data showed that vaccinated mice could prevent tumor recurrence, increase T-cell infiltration in the metastatic tumor, and prolong the survival curve. The mechanistic investigation by immunophenotyping revealed that rWTC-MBTA vaccination induced both effector memory (CD44+CD62L−) and center memory (CD44+CD62L+) T cells as well as increased overall CD4+ and CD8+ T-cell count while depletion experiments demonstrated that CD8+ T cells were required for vaccine efficacy. Isolated splenocytes co-cultured with 4T1 cells showed rWTC-MBTA significantly increased T-cell mediated cytotoxicity through TNF-a and IFN-γ in CD107a+CD4+ T cells and Granzyme B and IFN-γ in CD107a+CD8+ T cells. In all experiments, vaccination exerted negligible systemic toxicity. Collectively, our study demonstrates that the rWTC-MBTA vaccine is a safe and promising therapeutic option to prevent and treat tumor metastasis by triggering an antitumor immune response. Citation Format: Juan Ye, Herui Wang, Mitchell Sun, Ondrej Uher, Mark R. Gilbert, Karel Pacak, Zhengping Zhuang, Rogelio Medina, Samik Chakraborty, Jan Zenka. Unique autologous cancer vaccine comprised of irradiated whole tumor cells and MBTA (rWTC-MBTA) triggers antitumor immune response to prevent metastasis. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6800.

Development and Assessment of Innovative High-Fidelity Simulation Vaccination Course Integrating Emergency Cases for Pharmacy Undergraduates-A Randomized Controlled Study.

Recently, pharmacists in Germany were allowed to administer influenza and COVID-19 vaccines for people aged 12 years and older in order to increase vaccination coverage rates. In order to adapt the pharmacy curriculum for clinical practice, an innovative, vaccination training course using a high-fidelity simulator (HFS) was developed, implementing clinical scenarios to manage adverse events. In a randomized controlled trial using a pre and post design with pharmacy undergraduates, the intervention group interacted with an HFS, while the control group was trained with low-fidelity injection pads. Before and after the respective training, each participant went through an objective structured clinical examination (OSCE) and completed a self-assessment questionnaire and knowledge quiz. Both training methods showed a significant increase in skills, but there was also a significant greater increase in the intervention group when compared to the control group, particularly with respect to the vaccination process. Furthermore, every individual in the intervention group improved from the pre- to post-training OSCEs. Therefore, HFS has been proven to be an appropriate tool to train pharmacy students for the purposes of vaccine administration and to prepare for future challenges. Particularly, recognizing and managing adverse reactions can be addressed in a very effective way.

Evaluating Use of the Octreotide Acetate Pen Injector in a Summative Human Factors Validation Study

ObjectiveSubcutaneous injections of octreotide acetate require chronic administration by health care providers (HCPs). We aimed to validate the safe and effective use of the octreotide acetate pen injector, its labeling, and instructions for use (IFU) by patients, caregivers, and HCPs and to mitigate use-related risks. MethodsThis summative human factors validation study enrolled adults with neuroendocrine tumors and related diarrhea or flushing, adult caregivers, and HCPs. Before simulated use, participants self-familiarized as desired. Each participant was assigned 1 injection site for administration into an injection pad. The first of 2 unaided injections assessed first use and required priming; the second assessed routine use and dose change. Participants gave subjective feedback after each injection and completed knowledge probes and reading comprehension questions after the second injection. ResultsThe study enrolled 45 participants (15 per group). Forty-two participants completed the first injection successfully by administering the dose correctly. Three participants did not dose successfully; 3 failed to prime the pen, and 1 failed to dial the correct dose. Besides dosing, 2 participants failed to remove the needle after injection. Forty-four participants completed the second injection, but 1 participant failed to dial the correct dose. No other errors were observed. Overall success rates on knowledge probes and reading comprehension questions were 99.1% and 99.6%, respectively. All participants found the IFU easy to follow and understand. ConclusionThe octreotide acetate pen injector, labeling, and IFU enabled intended users to administer subcutaneous octreotide safely and effectively. The residual risks of use are low and acceptable.

Semaglutide single-dose pen-injector: Post hoc analysis of summative usability testing for weight management.

Subcutaneous semaglutide, at a 2.4 mg once‐weekly maintenance dose, is approved in the United States for weight management in individuals with a body mass index (BMI) of 30 kg/m2 or higher, or with a BMI of 27 kg/m2 or higher and at least one obesity‐related co‐morbidity. To investigate the usability of the semaglutide pen‐injector in individuals who met these criteria, we report post hoc analysis of the summative (human factors validation) usability testing and safety analysis involving patients with type 2 diabetes (an obesity‐related co‐morbidity) with the same pen‐injector, limited to the 26 out of 30 patients with a BMI of 27 kg/m2 or higher (11 pen‐injector–naïve, 15 pen‐injector–experienced) and 15 non‐pharmacist healthcare professionals (HCPs). Participants performed two simulated injections into an injection pad. No potentially serious use errors occurred. Mean subjective ease‐of‐use rating on a seven‐point scale, where 1 = difficult and 7 = easy, was 6.9 for the second injection in all three groups. These results suggest that the semaglutide pen‐injector is easy to use and not associated with serious use errors when used by pen‐injector–naïve or pen‐injector–experienced patients meeting the requirement for weight management with semaglutide treatment, and by non‐pharmacist HCPs.

Large Volume CO2 Storage and Plume Management in the Southeastern U.S.; Reservoir Characterization and Simulation

This paper summarizes a reservoir simulation study to evaluate the potential storage of 675 million metric tons of CO2 over 30 years at the Project ECO2S storage site—a 12,000-hectare storage complex adjacent to Mississippi Power Company’s (MPC) Plant Ratcliffe facility in Kemper County, Mississippi, USA. The project team studied the storage capacity of the target formations, estimated the CO2 plume size, performed a sensitivity analysis to examine the influence of reservoir and fluid properties, and tested the impact of active plume management—a process that includes extracting water from down-dip water production wells and re-injecting it through up-dip water injection wells within the storage formation—on CO2 plume migration and its extent. The ECO2S site appears to be capable of storing captured CO2 emissions from multiple Southern Company operated power sources, which together emit 22.5 million metric tons per year (675 million metric tons over 30 years). To investigate field development strategies for large volume CO2 injection and storage at ECO2S, the project team developed a base model using the latest geological interpretation. Thirty years of CO2 injection is simulated through seven injection pads with each pad hosting three injection wells, positioned in the center of the potential storage site, followed by 30 years of CO2 plume monitoring. The simulation results show that the 675 million metric tons of CO2 can be injected into the storage formations, safely and securely. The largest CO2 plume, which occurs in the shallowest reservoir, covers a 202-square kilometer area. Active plume management shows a small impact on controlling the plume size and its migration due to extremely high vertical permeability minimizing the impact of the water curtain. Project ECO2S is part of the CarbonSAFE Program and is financially supported by the USDOE-NETL and Mississippi Power Company. The project is managed by the Southern States Energy Board. Technical Support is provided by Southern Company Research and Development.

Creation and propagation of a single magnetic domain wall in 2D nanotraps with a square injection pad

Polycrystalline permalloy 2D nanotraps with a thickness of 20 nm were studied using a Lorentz microscope associated with micro-magnetic simulations. Each trap was designed to create a single head-to-head domain wall. The traps consist of a few nanowires with an in-plane dimension of w nm × 1000 nm (w = 150, 200 and 250 nm). Some structures with an injection pad were also designed to create a single domain wall and propagate it through the structure with the said injection pad. A few of them were patterned to study the nucleation and propagation behavior of such nucleated domain walls using both horizontal magnetic field and injection pad approaches. The case of a domain wall created at the first corner of the trap with a wire width of 200 nm was systematically studied, while single and multiple domain walls can also be created and propagated with or without an injection structure. The characteristics of such movements were exploited with an emphasis on a single head-to-head domain wall.

MON-LB47 An International Simulated Use Study (PRESTO) to Evaluate Nurse Preferences Between the Lanreotide Autogel New Syringe and Octreotide Long-Acting Release Syringe

Background: A new lanreotide autogel/depot (LAN) syringe was developed based on feedback from a human factors study to improve user experience. Methods: PRESTO was a multinational, simulated-use study in nurses with ≥2 years’ experience injecting LAN or octreotide long-acting release (OCT LAR) in patients with acromegaly and/or neuroendocrine tumors, which aimed to assess injector preference between the LAN new syringe and the current OCT LAR syringe. Participating nurses were invited to test both the LAN new syringe (120 mg) and the current OCT LAR syringe (20 mg or 30 mg), using injection pads. The sponsor was not involved in these sessions. In an anonymous web-based questionnaire, nurses reported overall preference (‘strong’ or ‘slight’; primary endpoint), and rated and ranked the importance of nine attributes for each syringe (1 [not at all] to 5 [very much]). Results: In total, 90 nurses attended injection sessions and completed valid questionnaires. Overall, 97.8% of nurses expressed a preference (85.6% ‘strong’, 12.2% ‘slight’) for LAN new syringe (p<0.0001 vs current OCT LAR). Attribute performance ratings were consistently higher for LAN new syringe vs current OCT LAR, with the greatest differences in ‘fast administration’ and ‘confidence the syringe will not be clogged’ (mean [standard deviation]: 2.6 [1.2] and 2.3 [1.5], respectively; p<0.0001). The attribute ranked most important was ‘confidence the syringe will not be clogged’ (24.4%) and least important was ‘convenience of syringe format, including packaging, from preparation to injection’ (34.4%). Conclusions: The PRESTO study showed that nurses preferred the user experience of the LAN new syringe over the current OCT LAR syringe across all attributes tested.

Assessing patient PREFERence between the dulaglutide pen and the semaglutide pen: A crossover study (PREFER).

AimWhen selecting treatments for type 2 diabetes (T2D), it is important to consider not only efficacy and safety, but also other treatment attributes that have an impact on patient preference. The objective of this study was to examine preference between injection devices used for two weekly GLP‐1 receptor agonists.Materials and MethodsThe PREFER study was an open‐label, multicentre, randomized, crossover study assessing patient preference for dulaglutide and semaglutide injection devices among injection‐naïve patients receiving oral medication for type 2 diabetes. After being trained to use each device, participants performed all steps of injection preparation and administered mock injections into an injection pad. Time‐to‐train (TTT) for each device was assessed in a subset.ResultsThere were 310 evaluable participants (48.4% female; mean age, 60.0 years; 78 participants in the TTT subgroup). More participants preferred the dulaglutide device than the semaglutide device (84.2% vs. 12.3%; P < 0.0001). More participants perceived the dulaglutide device to have greater ease of use (86.8% vs. 6.8%; P < 0.0001). After preparing and using the devices, more participants were willing to use the dulaglutide device (93.5%) than the semaglutide device (45.8%). Training participants to use the dulaglutide device required less time than the semaglutide device (3.38 vs. 8.14 minutes; P < 0.0001).ConclusionsParticipants with type 2 diabetes preferred the dulaglutide injection device to the semaglutide injection device. If patients prefer a device, they may be more willing to use the medication, which could result in better health outcomes. Furthermore, a shorter training time for injection devices may be helpful in busy clinical practice settings.

The Impact of a Training Device on Perception and Performance by Novice Users of an Autoinjector

The study was conducted to understand the effects of having access to different training materials in the interim between training and first use of an injection device for 27 injection-naïve participants. Participants were told they would be giving themselves a real injection of saline in the return session, and were not told that they would use injection pads until after subjective data was gathered during session 2. This deception paradigm was used to increase the external validity of the study. Participants self-trained in one of three conditions based on what they were given to take home: instructions for use, mechanical trainer, and/or a training video. Participants self-trained in session 1, performed a simulated injection in the session 2 two weeks later, and completed three online surveys in the interim. In session 2, a majority of participants were able to achieve minimally acceptable performance to deliver the medication during the simulated use of the autoinjector. Participants who took home a mechanical trainer had fewer use deviations than those who did not have the trainer at home. This difference was only seen in injection specific subtasks; performance on pre- and post-injection subtasks was low across all groups. Intermittent practice with a mechanical trainer was seen to improve performance on subtasks involved in the motor performance of the injection itself but did not impact performance or compliance with other tasks important to the injection. More holistic training solutions may be required to impact other aspects of the injection beyond the injection itself. While performance differed, subjective ratings did not differ, showing an overconfidence bias that may affect a user’s ability to self-report competence in device use.

Evaluation of performance, acceptance, and compliance of an auto-injector in healthy and rheumatoid arthritic subjects measured by a motion capture system.

PurposeThe study aimed to develop a motion capture system that can track, visualize, and analyze the entire performance of self-injection with the auto-injector.MethodsEach of nine healthy subjects and 29 rheumatoid arthritic (RA) patients with different degrees of hand disability performed two simulated injections into an injection pad while six degrees of freedom (DOF) motions of the auto-injector and the injection pad were captured. We quantitatively measured the performance of the injection by calculating needle displacement from the motion trajectories. The max, mean, and SD of needle displacement were analyzed. Assessments of device acceptance and usability were evaluated by a survey questionnaire and independent observations of compliance with the device instruction for use (IFU).ResultsA total of 80 simulated injections were performed. Our results showed a similar level of performance among all the subjects with slightly larger, but not statistically significant, needle displacement in the RA group. In particular, no significant effects regarding previous experience in self-injection, grip method, pain in hand, and Cochin score in the RA group were found to have an impact on the mean needle displacement. Moreover, the analysis of needle displacement for different durations of injections indicated that most of the subjects reached their personal maximum displacement in 15 seconds and remained steady or exhibited a small amount of increase from 15 to 60 seconds. Device acceptance was high for most of the questions (ie, >4; >80%) based on a 0–5-point scale or percentage of acceptance. The overall compliance with the device IFU was high for the first injection (96.05%) and reached 98.02% for the second injection.ConclusionWe demonstrated the feasibility of tracking the motions of injection to measure the performance of simulated self-injection. The comparisons of needle displacement showed that even RA patients with severe hand disability could properly perform self-injection with this auto-injector at a similar level with the healthy subjects. Finally, the observed high device acceptance and compliance with device IFU suggest that the system is convenient and easy to use.

Abstract 1020: Autophagy forms part of a metabolic switch during epithelial-to-mesenchymal transition and metastasis in a murine claudin-low breast cancer model

Abstract Epithelial-to-mesenchymal transition (EMT), the process through which epithelial cells gain mesenchymal characteristics including reduced adhesion and enhanced invasion, is a critical step in progression of cancer cells toward metastasis. However, the molecular mechanisms governing this process remain poorly understood. Furthermore, though metastasis is the cause of 90% of cancer deaths, no targeted therapy is currently available for metastatic disease. Metabolic reprogramming is a key feature of most cancer cells, with oxidative phosphorylation often being switched off in favor of glycolytic and synthetic pathways. Autophagy is a catabolic process in which protein complexes, damaged organelles and other macromolecules are lysosomally degraded. Autophagy can promote cancer cell survival, providing protein, lipid, nucleic acid and membrane precursors as well as auxiliary energy during periods of energy stress. The role of metabolism in EMT and metastasis has not been well studied. We hypothesized that the transition to metastasis involves metabolic alterations, including activation of autophagy. Previously, we derived (from a spontaneous mammary tumor in an MMTV-Wnt transgenic mouse) epithelial-like (E-Wnt) and mesenchymal-like (M-Wnt) cell lines, which recapitulate basal-like and claudin-low and breast tumors, respectively. Here, a metastatic derivative of M-Wnt cells was generated from lung metastases following serial passages in a severe combined immunodeficient (SCID) mouse. metM-Wnt cells were more proliferative, invasive and formed more colonies in soft agar than their parental M-Wnt cell line. Tail vein injection or mammary fat pad orthotopic implantation of metM-Wnt cells resulted in metastatic tumor formation in either the lungs or liver as detected by IVIS imaging and histological analysis. metM-Wnt cells displayed higher rates of glycolysis and oxidative phosphorylation, indicating that these cells are highly energetic. Furthermore, M-Wnt and metM-Wnt cells and tumors were found to have increased autophagic flux, as measured by LC3B expression and cleavage compared to E-Wnt cells and tumors. metM-Wnt cells were more sensitive to autophagy inhibition (either via chloroquine treatment or knockout of Atg5, a key component of the autophagic machinery) than M-Wnt or E-Wnt cells. Conversely, metM-Wnt cells were resistant to treatment with rapamycin, concomitant with sustained activation of mTOR, which controls many metabolic pathways including autophagy and protein synthesis. These results indicate that metabolic alteration is a feature of EMT in claudin-low breast cancer, including increased glycolysis, oxidative phosphorylation and autophagy. Furthermore, metastatic breast cancer cells may be more reliant on autophagy than non-metastatic cells, and autophagy may therefore be a therapeutic target in which to treat metastatic breast cancers. Citation Format: Ciara H. O’Flanagan, Emily L. Rossi, Stephen D. Hursting. Autophagy forms part of a metabolic switch during epithelial-to-mesenchymal transition and metastasis in a murine claudin-low breast cancer model. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1020.

Does one-to-one demonstration with insulin pads by health-care providers improves the insulin administration techniques among diabetic patients of a Tertiary Care Teaching Hospital in South India?

Objectives:The study was aimed to capture the effect of using injection pads as a tool in educating the diabetic patients who were on insulin. The attitude and practice of the patients in storage of insulin vials and disposal of insulin syringes were also assessed.Materials and Methods:A facility based Quasi-experimental study was carried out among the diabetic patients on insulin, attending diabetic clinic in endocrinology OPD in a tertiary care hospital, Puducherry. One to one intervention was given to the study participants or their attendants (who were involved in injecting insulin), by a trained investigator regarding all the steps of insulin administration. The insulin administration practices before and immediately after the intervention was assessed using a checklist.Results:In total 91 patients were included for the study with mean (SD) age of 53.9 (10.6) years and of them 76% were females. The attitude and practices of the study participants, such as hand washing before handling insulin, checking the expiry date, storage of insulin, inspection of injection site, rolling and cleaning the vial, withdrawal of the syringe up to the required dose, pushing the plunger after inserting the syringe into the vial, checking and removal of air bubbles, cleaning the injection site and allow to dry and injection technique improved significantly after the intervention (P < 0.05).Conclusion:This study findings shows that using injection pads for educating patients helps them to practise better insulin administration. The findings from the study can be applied in routine care and has to be explored further in diabetic patient management.

Effects of Magnetic Domain Walls on the Anisotropic Magnetoresistance in NiFe Nanowires.

We show that a type of magnetic domain walls (DWs) can be monitored by anisotropic magnetoresistance (AMR) measurements due to a specific DW volume depending on the DW type in NiFe magnetic wires. A circular DW injection pad is used to generate DWs at a low magnetic field, resulting in reliable DW introduction into magnetic wires. DW pinning is induced by a change of DW energy at an asymmetric single notch. The injection of DW from the circular pad and its pinning at the notch is observed by using AMR and magnetic force microscope (MFM) measurements. A four-point probe AMR measurement allows us to distinguish the DW type in the switching process because DWs are pinned at the single notch, where voltage probes are closely placed around the notch. Two types of AMR behavior are observed in the AMR measurements, which is owing to a change of DW structures. MFM images and micromagnetic simulations are consistent with the AMR results.

Attenuating effect of chrysin on experimental autoimmune uveitis and its mechanism

Background Chrysin has many biological activities, and its anti-inflammatory effect has been confirmed. However, whether it can treat experimental autoimmune uveitis (EAU) is still not elucidated. Objective This study was to investigate the therapeutic effect of chrysin on EAU and explore the potential mechanism. Methods EAU animal models were established in 30 SPF C57BL/6J mice by the subcutaneous injection and ball pad injection of interphotoreceptor retinoid binding protein1-20 (IRBP1-20)/complete Freund adjuvant (CFA), and then the models were randomized into the model control group and chrysin-treated group. Chrysin solution dissolved by 10 μl dimethyl sulfoxide (DMSO)+ 140 μl PBS was administrated by gavaging in the mice with the dose 25 mg/kg from 3 days before immunization through 21 days everyday in the chrysin group, and equal volume of solvent was used in the same way in the model control group. Retinas were examined by indirect ophthalmoscope once per day, and inflammation and pathological scores of retina were performed based on the criteria of Caspi on the 21st day after injection. The apoptosis of retinal cells was assayed by TUNEL staining, and the relative expressions of pro-inflammatory cytokines interferon-γ (IFN-γ), interleukin-17A (IL-17A), IL-6 and tumor necrosis factor-α (TNF-α) and signal transducer and activator of transcription 1 (STAT1), STAT3, p-STAT1, p-STAT3 in mouse retinas were detected by Western blot. Results Compared with the model control group, the inflammation scores and pathological scores of retinal inflammation were significantly reduced in the chrysin group (inflammation scores: 0.50±0.45 vs 1.58±0.92, t=2.600, P=0.026; pathologic scores: 0.58±0.38 vs 1.83±0.75, t=3.638, P=0.005). The infiltration of a large number of inflammatory cells, retinal vasculitis and granulomatous lesions were found in mouse retinas in the model control group, however, the morphology of mouse retinas in the chrysin group was normal based on hematoxylin-eosin staining. The number of apoptotic cells was remarkable lessened in the chrysin group compared with the model control group under the fluorescence microscope. Western blot assay resolved that significantly down-regulation in the expressions of IFN-γ, IL-17A, IL-6 and TNF-α was seen in the chrysin group in comparison with the model control group (t=7.802, P=0.001; t=14.906, P=0.000; t=10.241, P=0.001; t=3.304, P=0.030), and the relative expression levels of STAT1, STAT3, p-STAT1 and p-STAT3 were considerably lower in the chrysin group than those in the model control group (t=8.965, P=0.001; t=8.358, P=0.001; t=4.864, P=0.031; t=4.730, P=0.009). Conclusions Chrysin or chrysin-like flavonoids ameliorate intraocular inflammatory symptoms in EAU mice by inhibiting the activity of STAT signal pathway. Key words: Flavonoids/pharmacology; Immunosuppressive agents/pharmacology; Autoimmune diseases; Uveitis/immunology; Disease models, animal; Signal transducer and activator of transcription; T-lymphocytes/drug effects

Usability of a new disposable autoinjector platform device: results of a formative study conducted with a broad user population.

This article presents a late-stage formative usability study of an autoinjector platform device. Such devices are used for the subcutaneous delivery of biopharmaceuticals, primarily for self-administration by the patient. Previous usability work on autoinjectors reported in the literature has been specific to single indications. This study was instead conducted with a broad user population, defined to represent user characteristics across a range of indications. The goals of the study were to evaluate whether users could use the devices safely and effectively, and could understand the instructions for use (IFU) as well as the accompanying training. Further objectives were to capture any usability issues and to obtain participants’ subjective ratings on the IFU and training as well as the confidence and comfort in using the device. A total of 43 participants in 5 groups received training and performed simulated injections either into an injection pad or a mannequin. All participants were able to successfully use the device. The device was well appreciated by all users, with a reported degree of confidence in using the device of 98%, of user comfort of 93%, and of comprehensibility of IFU and training of 98%. These values are higher than other comparable results reported in the literature. The presence of both audible and visible feedback during injection was seen to be a significant factor contributing to injection success. The observation that the device can be safely and efficiently used by all tested user groups provides confidence that the device and IFU in their current form will pass future summative testing in specific applications.