Lipid analysis at the molecular species level represents a valuable opportunity for clinical applications due to the essential roles that lipids play in metabolic health. However, a comprehensive... Show moreLipid analysis at the molecular species level represents a valuable opportunity for clinical applications due to the essential roles that lipids play in metabolic health. However, a comprehensive and high-throughput lipid profiling remains challenging given the lipid structural complexity and exceptional diversity. Herein, we present an 'omic-scale targeted LC-MS/MS approach for the straightforward and high-throughput quantification of a broad panel of complex lipid species across 26 lipid (sub)classes. The workflow involves an automated single-step extraction with 2-propanol, followed by lipid analysis using hydrophilic interaction liquid chromatography in a dual-column setup coupled to tandem mass spectrometry with data acquisition in the timed selective reaction monitoring mode (12 min total run time). The analysis pipeline consists of an initial screen of 1903 lipid species, followed by high-throughput quantification of robustly detected species. Lipid quantification is achieved by a single-point calibration with 75 isotopically labeled standards representative of different lipid classes, covering lipid species with diverse acyl/alkyl chain lengths and unsaturation degrees. When applied to human plasma, 795 lipid species were measured with median intra-and inter-day precisions of 8.5 and 10.9%, respectively, evaluated within a single and across multiple batches. The concentration ranges measured in NIST plasma were in accordance with the consensus intervals determined in previous ring-trials. Finally, to benchmark our workflow, we characterized NIST plasma materials with different clinical and ethnic backgrounds and analyzed a sub-set of sera (n = 81) from a clinically healthy elderly population. Our quantitative lipidomic platform allowed for a clear distinction between different NIST materials and revealed the sex-specificity of the serum lipidome, highlighting numerous statistically significant sex differences. Show less
Background As provisions of mental healthcare services to military and veteran populations increases the risk to service providers developing secondary traumatic stress (STS), efforts are needed to... Show moreBackground As provisions of mental healthcare services to military and veteran populations increases the risk to service providers developing secondary traumatic stress (STS), efforts are needed to examine the impact of delivering novel interventions which may include 3MDR. As a virtual-reality supported intervention, 3MDR exposes the patient, therapist and operator to graphic and sensory stimuli (i.e. narratives, imagery, smells, and music) in the course of the intervention. 3MDR is actively being researched at multiple sites internationally within military and veteran populations. It is, therefore, crucial to ensure the safety and wellbeing of 3MDR therapists and operators who are exposed to potentially distressing sensory stimuli. Objective The purpose of this study is to qualitatively examine the impact and experiences of STS amongst therapists and operators in delivering 3MDR. For this study, impact will be defined as therapists or operators experiencing perceived STS as a result of delivering 3MDR. Methods This exploratory qualitative study recruited 3MDR therapists and operators (N = 18) from Canada, the Netherlands, the United Kingdom, and the United States who had previously delivered 3MDR therapy. Telephone or video-conferencing interviews were used to gather data that was subsequently transcribed and thematically analyzed. Results Four themes emerged among the therapists (n = 13) and operators (n = 5): (1) personal cost and benefits of 3MDR, (2) professional paradox of a 3MDR therapist, (3) perceived effect of 3MDR on patients, and (4) recommendations for future 3MDR use. Conclusions STS was not noted to be a significant challenge for 3MDR therapists and operators. Future research may investigate optimal means of providing training and ongoing support for 3MDR therapists and operators. Show less
Objective Military members and veterans are at elevated risk of treatment-resistant posttraumatic stress disorder (TR-PTSD) due to higher rates of exposure to potentially traumatic events during... Show moreObjective Military members and veterans are at elevated risk of treatment-resistant posttraumatic stress disorder (TR-PTSD) due to higher rates of exposure to potentially traumatic events during the course of duty. Knowledge of TR-PTSD is limited, and specific protocols or evidence-based TR-PTSD therapies are lacking. Multimodal motion-assisted memory desensitization and reconsolidation (3MDR) therapy is an emerging intervention for combat-related TR-PTSD. The purpose of this study was to preliminarily assess the effectiveness of 3MDR in addressing TR-PTSD in Canadian military members and veterans. Methods This study is a longitudinal mixed-methods clinical trial. English-speaking military members and veterans aged 18-60 with TR-PTSD were recruited to participate. The intervention consisted of six sessions of 3MDR therapy. Quantitative data were collected pretreatment, posttreatment, and longitudinally at 1, 3, and 6 months after completion of 3MDR. Results Results from the first 11 participants to complete the 3MDR protocol exhibited statistically significant improvement (surviving multiple comparison correction) in clinically administered and self-reported scores for PTSD (CAPS-5 and PCL-5), moral injury (MISS-M-SF), depression (PHQ-9), anxiety (GAD-7), emotional regulation (DERS-18), and resilience (CD-RS-25). Conclusion The preliminary and exploratory results from this clinical trial support the growing body of literature illustrating 3MDR as an effective treatment for military-related TR-PTSD. These results are notable given participants' previous lack of success with frontline psychotherapeutic and pharmacological interventions. Given that there are currently very limited treatment options for TR-PTSD, 3MDR could prove to be a valuable treatment option for military members and veterans with TR-PTSD. Show less
Background: In recent years, the delivery of evidence-based therapies targeting posttraumatic stress disorder (PTSD) has been the focus of the Departments of Defense in countries such as Canada,... Show moreBackground: In recent years, the delivery of evidence-based therapies targeting posttraumatic stress disorder (PTSD) has been the focus of the Departments of Defense in countries such as Canada, the Netherlands, and the United States. More than 66% of military members continue to experience symptoms of PTSD that significantly impact their daily functioning and quality of life after completing evidence-based treatments. Innovative, engaging, and effective treatments for PTSD are needed. Multimodal motion-assisted memory desensitization and reconsolidation (3MDR) is an exposure-based, virtual reality-supported therapy used to treat military members and veterans with treatment-resistant PTSD. Given the demonstrated efficacy of 3MDR in recently published randomized control trials, there is both an interest in and a need to adapt the intervention to other populations affected by trauma and to improve accessibility to the treatment.Objective: We aimed to further innovate, develop, and validate new and existing hardware and software components of 3MDR to enhance its mobility, accessibility, feasibility, and applicability to other populations affected by trauma, including public safety personnel (PSP), via international collaboration.Methods: This study used a modified Delphi expert consultation method and mixed methods quasi-experimental validation with the purpose of software validation among PSP (first responders, health care providers) participants (N=35). A team of international experts from the Netherlands, the United States, and Canada met on the web on a weekly basis since September 2020 to discuss the adoption of 3MDR in real-world contexts, hardware and software development, and software validation. The evolution of 3MDR hardware and software was undertaken followed by a mixed methods software validation study with triangulation of results to inform the further development of 3MDR.Results: This study resulted in the identification, description, and evolution of hardware and software components and the development of new 3MDR software. Within the software validation, PSP participants widely acknowledged that the newly developed 3MDR software would be applicable and feasible for PSP affected by trauma within their professions. The key themes that emerged from the thematic analysis among the PSP included the desire for occupationally tailored environments, individually tailored immersion, and the applicability of 3MDR beyond military populations.Conclusions: Within the modified Delphi consultation and software validation study, support for 3MDR as an intervention was communicated. PSP participants perceived that 3MDR was relevant for populations affected by trauma beyond military members and veterans. The resulting hardware and software evolution addressed the recommendations and themes that arose from PSP participants. 3MDR is a novel, structured, exposure-based, virtual reality-supported therapy that is currently used to treat military members and veterans with PTSD. Going forward, it is necessary to innovate and adapt 3MDR, as well as other trauma interventions, to increase effectiveness, accessibility, cost-effectiveness, and efficacy among other populations affected by trauma. Show less
Background: Military members and veterans exhibit higher rates of injuries and illnesses such as posttraumatic stress disorder (PTSD) because of their increased exposure to combat and other... Show moreBackground: Military members and veterans exhibit higher rates of injuries and illnesses such as posttraumatic stress disorder (PTSD) because of their increased exposure to combat and other traumatic scenarios. Novel treatments for PTSD are beginning to emerge and increasingly leverage advances in gaming and other technologies, such as virtual reality. Without assessing the degree of technology acceptance and perception of usability to the end users, including the military members, veterans, and their attending therapists and staff, it is difficult to determine whether a technology-based treatment will be used successfully in wider clinical practice. The Unified Theory of Acceptance and Use of Technology model is commonly used to address the technology acceptance and usability of applications in 5 domains.Objective: Using the Unified Theory of Acceptance and Use of Technology model, the purpose of this study was to determine the technology acceptance and usability of multimodal motion-assisted memory desensitization and reconsolidation (3MDR) on a virtual reality system in the primary user group (military members and veterans with treatment-resistant PTSD, 3MDR therapists, and virtual reality environment operators).Methods: This mixed methods embedded pilot study included military members (n=3) and veterans (n=8) with a diagnosis of combat-related PTSD, as well as their therapists (n=13) and operators (n=5) who completed pre-post questionnaires before and on completion of 6 weekly sessions of 3MDR. A partial least squares structural equation model was used to analyze the questionnaire results. Qualitative data from the interviews were assessed using thematic analysis.Results: Effort expectancy, which was the most notable predictor of behavioral intention, increased after a course of 3MDR with the virtual reality system, whereas all other constructs demonstrated no significant change. Participants' expectations of the technology were met, as demonstrated by the nonsignificant differences in the pre-post scores. The key qualitative themes included feasibility and function, technical support, and tailored immersion.Conclusions: 3MDR via a virtual reality environment appears to be a feasible, usable, and accepted technology for delivering 3MDR to military members and veterans who experience PTSD and 3MDR therapists and operators who facilitate their treatment. Show less
Introduction: Military members and Veterans are at risk of developing combat-related, treatment-resistant posttraumatic stress disorder (TR-PTSD) and moral injury (MI). Conventional trauma-focused... Show moreIntroduction: Military members and Veterans are at risk of developing combat-related, treatment-resistant posttraumatic stress disorder (TR-PTSD) and moral injury (MI). Conventional trauma-focused therapies (TFTs) have shown limited success. Novel interventions including Multi-modal Motion-assisted Memory Desensitization and Reconsolidation therapy (3MDR) may prove successful in treating TR-PTSD.Objective: To qualitatively study the experiences of Canadian military members and Veterans with TR-PTSD who received the 3MDR intervention.Methods: This study explored qualitative data from a larger mixed-method waitlist control trial testing the efficacy of 3MDR in military members and veterans. Qualitative data were recorded and collected from 3MDR sessions, session debriefings and follow-up interviews up to 6 months post-intervention; the data were then thematically analyzed.Results: Three themes emerged from the data: (1) the participants' experiences with 3MDR; (2) perceived outcomes of 3MDR; and (3) keys to successful 3MDR treatment. Participants expressed that 3MDR provided an immersive environment, active engagement and empowerment. The role of the therapist as a coach and "fireteam partner" supports the participants' control over their therapy. The multi-modal nature of 3MDR, combining treadmill-walking toward self-selected trauma imagery with components of multiple conventional TFTs, was key to helping participants engage with and attribute new meaning to the memory of the traumatic experience.Discussion: Preliminary thematic analysis of participant experiences of 3MDR indicate that 3MDR has potential as an effective intervention for combat-related TR-PTSD, with significant functional, well-being and relational improvements reported post-intervention.Conclusion: Military members and Veterans are at risk of developing TR-PTSD, with worse outcomes than in civilians. Further research is needed into 3MDR and its use with other trauma-affected populations. Show less
Multi-modal motion-assisted memory desensitization and reconsolidation therapy (3MDR), an interactive, virtual reality-assisted, exposure-based intervention for PTSD, has shown promising results... Show moreMulti-modal motion-assisted memory desensitization and reconsolidation therapy (3MDR), an interactive, virtual reality-assisted, exposure-based intervention for PTSD, has shown promising results for treatment-resistant posttraumatic stress disorder (TR-PTSD) among military members (MMs) and veterans in randomized controlled trials (RCT). Previous research has suggested that emotional regulation (ER) and emotional dysregulation (ED) may be factors which are correlated with symptom severity and maintenance of TR-PTSD. This embedded mixed-methods pilot study (n = 9) sought to explore the impact of 3MDR on ER and ED of MMs and veterans. Difficulties in Emotional Regulation Scale (DERS-18) data were collected at baseline, prior to each session, and at one week, one month, and three months postintervention and analyzed. Qualitative data collected from sessions, debriefs, and follow-up interviews were transcribed and descriptively analyzed. Results demonstrated statistically significant decreases in DERS-18 scores from preintervention to postintervention at each timepoint. Qualitatively, participants perceived improvements in ER within specified DERS-18 domains. We describe how 3MDR's unique and novel approach addresses ED through cognitive-motor stimulation, narration, divergent thinking, reappraisal of aversive stimuli, dual-task processing, and reconsolidation of traumatic memories. More studies are needed to better understand the underlying neurobiological mechanisms by which 3MDR addresses ER and PTSD. Show less
Veelen, N. van; Boonekamp, R.C.; Schoonderwoerd, T.A.J.; Emmerik, M.L. van; Nijdam, M.J.; Bruinsma, B.; ... ; Vermetten, E. 2021
