Facing death, returning to life: A qualitative analysis of MDMA-assisted therapy for anxiety associated with life-threatening illness.

Anxiety associated with life-threatening illness (LTI) is a pervasive mental health issue with a wide impact. A spectrum of traditional pharmacotherapies and psychotherapies are available, but offer varying success in reducing symptoms and improving quality of life. We explore a novel therapy for this condition by assessing prominent thematic elements from participant narrative accounts of a pilot phase 2 clinical trial of 3,4 Methylenedioxymethamphetamine-Assisted Therapy (MDMA-AT) for treating anxiety associated with LTI. Semi-structured qualitative interviews were conducted with a subset of adult participants 3 months following completion of this trial. This qualitative analysis sought to complement, clarify, and expand upon the quantitative findings obtained from the clinical trial to further understand the process and outcomes of the treatment. Interviews were coded and analyzed using an Interpretative Phenomenological Analysis (IPA) methodological framework. Participants described in detail their experiences from before, during and after the trial, which were analyzed and categorized into thematic clusters. Specifically, participants explored what they felt were important elements of the therapeutic process including processing trauma and grief, exploring mystical and existential experiences, engaging with the present moment with reduced physiological activation, and facing illness and existential fears. Outcomes of the treatment included increased ability to cope with LTI, reduced psychological symptoms, improved vitality and quality of life, and feeling more resourced. Participant narratives also showed a reconnection to life and greater emotional resilience in response to trauma and medical relapse. These findings are compared to similar treatments for the same indication. Limitations and challenges encountered in conducting this study are discussed along with implications for theory and clinical treatment.

Novel Application of Photogrammetry to Quantify Fascicle Orientations of Female Cadaveric Pelvic Floor Muscles.

Although critical for understanding and simulating pelvic floor muscle function and pathophysiology, the fascicle arrangements of the coccygeus and levator ani remain mostly undetermined. We performed close-range photogrammetry on cadaveric pelvic floor muscles to robustly quantify surface fascicle orientations. The pelvic floor muscles of 5 female cadavers were exposed through anatomic dissections, removed en bloc, and photographed from every required angle. Overlapping images were mapped onto in silico geometries and muscle fascicles were traced manually. Tangent vectors were calculated along each trace; interpolated to define continuous, 3D vector fields; and projected onto axial and sagittal planes to calculate angles with respect to the pubococcygeal line. Contralateral and ipsilateral pelvic floor muscles were compared within each donor (Kuiper's tests) and using mean values from all donors (William-Watsons tests). Contralateral muscles and all but one ipsilateral muscle pair differed significantly within each donor (p < 0.001). When mean values were considered collectively, no contralateral or ipsilateral statistical differences were found but all muscles compared differed by more than 10° on average. Close-range photogrammetry and subsequent analyses robustly quantified surface fascicle orientations of the pelvic floor muscles. The continuous, 3D vector fields provide data necessary for improving simulations of the female pelvic floor muscles.

Proactive Air Management in CT Power Injections: A Comprehensive Approach to Reducing Air Embolization.

OBJECTIVE: Venous air embolism as a complication of contrast media administration from power injection systems in CT is found to occur in 7%-55% of patients, impacting patient safety, diagnostic image quality, workflow efficiency, and patient and radiographer satisfaction. This study reviews the challenges associated with reactive air management approaches employed on contemporary systems, proposes a novel air management approach using proactive methods, and compares the impact of reactive and proactive approaches on injected air volumes under simulated clinical use. METHODS: Injected air volumes from three power injection systems were measured under simulated clinical use via custom air trap fixture. Two of the systems employed reactive air management approaches, while a new system implemented the proposed proactive air management approach. RESULTS: The proactive system injected significantly less air (average of 0.005 mL ± 0.006 mL with a maximum of 0.017 mL) when compared to two systems with reactive approaches (averages of 0.130 mL ± 0.082 mL and 0.106 mL ± 0.094 mL with maximums of 0.259 mL and 0.311 mL, respectively) (p < 0.05). CT images were taken of static and dynamic 0.1 mL air bubbles inside of a vascular phantom, both of which were clearly visible. Additionally, the dynamic bubble was shown to introduce image artifacts similar to those observed clinically. CONCLUSION: Comparison of the injected air volumes show that a system with a proactive air management approach injected significantly less air compared to tested systems employing reactive approaches. SIGNIFICANCE: The results indicate that the use of a proactive approach could significantly reduce the prevalence of observable, and potentially artifact-inducing, venous air embolism in contrast-enhanced CT procedures.

Impact of CT Injector Technology and Contrast Media Viscosity on Vascular Enhancement: Evaluation in a Circulation Phantom.

OBJECTIVE: To assess the impact of piston-based vs peristaltic injection system technology and contrast media viscosity on achievable iodine delivery rates (IDRs) and vascular enhancement in a pre-clinical study. METHODS: Four injectors were tested: MEDRAD® Centargo, MEDRAD® Stellant, CT Exprès®, and CT motion™ using five contrast media [iopromide (300 and 370 mgI ml-1), iodixanol 320 mgI ml-1, iohexol 350 mgI ml-1, iomeprol 400 mgI ml-1]. Three experiments were performed evaluating achievable IDR and corresponding enhancement in a circulation phantom. RESULTS: Experiment I: Centargo provided the highest achievable IDRs with all tested contrast media (p < 0.05). Iopromide 370 yielded the highest IDR with an 18G catheter (3.15 gI/s); iopromide 300 yielded the highest IDR with 20G (2.70 gI/s) and 22G (1.65 gI/s) catheters (p < 0.05).Experiment II: with higher achievable IDRs, piston-based injectors provided significantly higher peak vascular enhancement (up to 48% increase) than the peristaltic injectors with programmed IDRs from 1.8 to 2.4 gI/s (p < 0.05).Experiment III: with programmed IDRs (e.g. 1.5 gI/s) achievable by all injection systems, Centargo, with sharper measured bolus shape, provided significant increases in enhancement of 34-73 HU in the pulmonary artery with iopromide 370 (p < 0.05). CONCLUSION: The tested piston-based injection systems combined with low viscosity contrast media provide higher achievable IDRs and higher peak vascular enhancement than the tested peristaltic-based injectors. With equivalent IDRs, Centargo provides higher peak vascular enhancement due to improved bolus shape. ADVANCES IN KNOWLEDGE: This paper introduces a new parameter to compare expected performance among contrast media: the concentration/viscosity ratio. Additionally, it demonstrates previously unexplored impacts of bolus shape on vascular enhancement.

Perceived Benefits of MDMA-Assisted Psychotherapy beyond Symptom Reduction: Qualitative Follow-Up Study of a Clinical Trial for Individuals with Treatment-Resistant PTSD.

We present select findings from a long-term follow-up qualitative study of MDMA-assisted psychotherapy for veterans, firefighters, and police officers suffering from chronic, treatment-resistant PTSD. Semi-structured qualitative interviews were conducted at participants' one-year follow-up after a recently completed phase 2 clinical trial. Available interviews from 19 of 24 participants were analyzed. This qualitative analysis sought to complement, clarify, and expand upon the quantitative findings obtained from the Clinician Administered PTSD Scale (CAPS-IV) and supported by the Long-Term Follow-Up (LTFU) Questionnaire. Pertinent data from interview transcripts were coded and analyzed using an interpretative phenomenological analysis (IPA) methodological framework. We explore prominent thematic elements from participant accounts to better understand the outcomes experienced in this trial. All participants reported experiencing lasting personal benefits and enhanced quality of life that extend beyond quantifiable symptom reduction. We explore a range of treatment benefits beyond symptom reduction to highlight the utility of qualitative investigations of the process and effects of MDMA-assisted psychotherapy. Limitations and challenges encountered in conducting this study are discussed along with recommendations for improved qualitative research protocols in future clinical trials.

Deformation of Transvaginal Mesh in Response to Multiaxial Loading.

Synthetic mesh for pelvic organ prolapse (POP) repair is associated with high complication rates. While current devices incorporate large pores (>1 mm), recent studies have shown that uniaxial loading of mesh reduces pore size, raising the risk for complications. However, it is difficult to translate uniaxial results to transvaginal meshes, as in vivo loading is multidirectional. Thus, the aim of this study was to (1) experimentally characterize deformation of pore diameters in a transvaginal mesh in response to clinically relevant multidirectional loading and (2) develop a computational model to simulate mesh behavior in response to in vivo loading conditions. Tension (2.5 N) was applied to each of mesh arm to simulate surgical implantation. Two loading conditions were assessed where the angle of the applied tension was altered and image analysis was used to quantify changes in pore dimensions. A computational model was developed and used to simulate pore behavior in response to these same loading conditions and the results were compared to experimental findings. For both conditions, between 26.4% and 56.6% of all pores were found to have diameters <1 mm. Significant reductions in pore diameter were noted in the inferior arms and between the two superior arms. The computational model identified the same regions, though the model generally underestimated pore deformation. This study demonstrates that multiaxial loading applied clinically has the potential to locally reduce porosity in transvaginal mesh, increasing the risk for complications. Computational simulations show potential of predicting this behavior for more complex loading conditions.

Extracellular matrix regenerative graft attenuates the negative impact of polypropylene prolapse mesh on vagina in rhesus macaque.

BACKGROUND: The use of wide pore lightweight polypropylene mesh to improve anatomical outcomes in the surgical repair of prolapse has been hampered by mesh complications. One of the prototype prolapse meshes has been found to negatively impact the vagina by inducing a decrease in smooth muscle volume and contractility and the degradation of key structural proteins (collagen and elastin), resulting in vaginal degeneration. Recently, bioscaffolds derived from extracellular matrix have been used to mediate tissue regeneration and have been widely adopted in tissue engineering applications. OBJECTIVE: Here we aimed to: (1) define whether augmentation of a polypropylene prolapse mesh with an extracellular matrix regenerative graft in a primate sacrocolpopexy model could mitigate the degenerative changes; and (2) determine the impact of the extracellular matrix graft on vagina when implanted alone. STUDY DESIGN: A polypropylene-extracellular matrix composite graft (n = 9) and a 6-layered extracellular matrix graft alone (n = 8) were implanted in 17 middle-aged parous rhesus macaques via sacrocolpopexy and compared to historical data obtained from sham (n = 12) and the polypropylene mesh (n = 12) implanted by the same method. Vaginal function was measured in passive (ball-burst test) and active (smooth muscle contractility) mechanical tests. Vaginal histomorphologic/biochemical assessments included hematoxylin-eosin and trichrome staining, immunofluorescent labeling of α-smooth muscle actin and apoptotic cells, measurement of total collagen, collagen subtypes (ratio III/I), mature elastin, and sulfated glycosaminoglycans. Statistical analyses included 1-way analysis of variance, Kruskal-Wallis, and appropriate post-hoc tests. RESULTS: The host inflammatory response in the composite mesh-implanted vagina was reduced compared to that following implantation with the polypropylene mesh alone. The increase in apoptotic cells observed with the polypropylene mesh was blunted in the composite (overall P < .001). Passive mechanical testing showed inferior parameters for both polypropylene mesh alone and the composite compared to sham whereas the contractility and thickness of smooth muscle layer in the composite were improved with a value similar to sham, which was distinct from the decreases observed with polypropylene mesh alone. Biochemically, the composite had similar mature elastin content, sulfated glycosaminoglycan content, and collagen subtype III/I ratio but lower total collagen content when compared to sham (P = .011). Multilayered extracellular matrix graft alone showed overall comparable values to sham in aspects of the biomechanical, histomorphologic, or biochemical endpoints of the vagina. The increased collagen subtype ratio III/I with the extracellular matrix graft alone (P = .033 compared to sham) is consistent with an ongoing active remodeling response. CONCLUSION: Mesh augmentation with a regenerative extracellular matrix graft attenuated the negative impact of polypropylene mesh on the vagina. Application of the extracellular matrix graft alone had no measurable negative effects suggesting that the benefits of this extracellular matrix graft occur when used without a permanent material. Future studies will focus on understanding mechanisms.

Textile properties of synthetic prolapse mesh in response to uniaxial loading.

BACKGROUND: Although synthetic mesh is associated with superior anatomic outcomes for the repair of pelvic organ prolapse, the benefits of mesh have been questioned because of the relatively high complication rates. To date, the mechanisms that result in such complications are poorly understood, yet the textile characteristics of mesh products are believed to play an important role. Interestingly, the pore diameter of synthetic mesh has been shown to impact the host response after hernia repair greatly, and such findings have served as design criteria for prolapse meshes, with larger pores viewed as more favorable. Although pore size and porosity are well-characterized before implantation, the changes in these textile properties after implantation are unclear; the application of mechanical forces has the potential to greatly alter pore geometries in vivo. Understanding the impact of mechanical loading on the textile properties of mesh is essential for the development of more effective devices for prolapse repair. OBJECTIVE: The objective of this study was to determine the effect of tensile loading and pore orientation on mesh porosity and pore dimensions. STUDY DESIGN: In this study, the porosity and pore diameter of 4 currently available prolapse meshes were examined in response to uniaxial tensile loads of 0.1, 5, and 10 N while mimicking clinical loading conditions. The textile properties were compared with those observed for the unloaded mesh. Meshes included Gynemesh PS (Ethicon, Somerville, NJ), UltraPro (Artisyn; Ethicon), Restorelle (Coloplast, Minneapolis, MN), and Alyte Y-mesh (Bard, Covington, GA). In addition to the various pore geometries, 3 orientations of Restorelle (0-, 5-, 45-degree offset) and 2 orientations of UltraPro (0-, 90-degree offset) were examined. RESULTS: In response to uniaxial loading, both porosity and pore diameter dramatically decreased for most mesh products. The application of 5 N led to reductions in porosity for nearly all groups, with values decreasing by as much as 87% (P < .05). On loading to 10 N of force, nearly all mesh products that were tested were found to have porosities that approached 0% and 0 pores with diameters >1 mm. CONCLUSION: In this study, it was shown that the pore size of current prolapse meshes dramatically decreases in response to mechanical loading. These findings suggest that prolapse meshes, which are more likely to experience tensile forces in vivo relative to hernia repair meshes, have pores that are unfavorable for tissue integration after surgical tensioning and/or loading in urogynecologic surgeries. Such decreases in pore geometry support the hypothesis that regional increases in the concentration of mesh leads to an enhanced local foreign body response. Although pore deformation in transvaginal meshes requires further characterization, the findings presented here provide a mechanical understanding that can be used to recognize potential areas of concern for complex mesh geometries. Understanding mesh mechanics in response to surgical and in vivo loading conditions may provide improved design criteria for mesh and a refinement of surgical techniques, ultimately leading to better patient outcomes.

Impact of parity on ewe vaginal mechanical properties relative to the nonhuman primate and rodent.

INTRODUCTION AND HYPOTHESIS: Parity is the leading risk factor for the development of pelvic organ prolapse. To assess the impact of pregnancy and delivery on vaginal tissue, researchers commonly use nonhuman primate (NHP) and rodent models. The purpose of this study was to evaluate the ewe as an alternative model by investigating the impact of parity on the ewe vaginal mechanical properties and collagen structure. METHODS: Mechanical properties of 15 nulliparous and parous ewe vaginas were determined via uniaxial tensile tests. Collagen content was determined by hydroxyproline assay and collagen fiber thickness was analyzed using picrosirius red staining. Outcome measures were compared using Independent samples t or Mann-Whitney U tests. ANOVA (Gabriel's pairwise post-hoc test) or the Welch Alternative for the F-ratio (Games Howell post-hoc test) was used to compare data with previously published NHP and rodent data. RESULTS: Vaginal tissue from the nulliparous ewe had a higher tangent modulus and tensile strength compared with the parous ewe (p < 0.025). The parous ewe vagina elongated 42 % more than the nulliparous ewe vagina (p = 0.015). No significant differences were observed in collagen structure among ewe vaginas. The tangent modulus of the nulliparous ewe vagina was not different from that of the NHP or rodent (p = 0.290). Additionally, the tangent moduli of the parous ewe and NHP vaginas did not differ (p = 0.773). CONCLUSIONS: Parity has a negative impact on the mechanical properties of the ewe vagina, as also observed in the NHP. The ewe may serve as an alternative model for studying parity and ultimately prolapse development.

The impact of boundary conditions on surface curvature of polypropylene mesh in response to uniaxial loading.

Exposure following pelvic organ prolapse repair has been observationally associated with wrinkling of the implanted mesh. The purpose of this study was to quantify the impact of variable boundary conditions on the out-of-plane deformations of mesh subjected to tensile loading. Using photogrammetry and surface curvature analyses, deformed geometries were accessed for two commercially available products. Relative to standard clamping methods, the amount of out-of-plane deformation significantly increased when point loads were introduced to simulate suture fixation in-vivo. These data support the hypothesis that regional increases in the concentration of mesh potentially enhance the host׳s foreign body response, leading to exposure.

Characterizing the ex vivo textile and structural properties of synthetic prolapse mesh products.

INTRODUCTION AND HYPOTHESIS: The use of polypropylene meshes for surgical repair of pelvic organ prolapse (POP) has been limited by complications, including mesh exposure, encapsulation, and pain. Numerous products are available with a wide array of textile and structural properties. It is thought that complications may be related, in part, to mesh structural properties. However, few descriptions of these properties exists to directly compare products. The aim of this study was to determine the textile and structural properties of five commonly used prolapse mesh products using a ball-burst failure protocol. METHODS: Porosity, anisotropic index, and stiffness of Gynemesh PS (n = 8), the prototype polypropylene mesh for prolapse repair, was compared with four newer-generation mesh produces: UltraPro (n = 5), SmartMesh (n = 5), Novasilk (n = 5), and Polyform (n = 5). RESULTS: SmartMesh was found to be the most porous, at 78 % ± 1.4 %. This value decreased by 21 % for Gynemesh PS (p < 0.001), 14 % for UltraPro and Novasilk (p < 0.001), and 28 % for Polyform (p < 0.001). Based on the knit pattern, SmartMesh and Polyform were the only products considered to be geometrically isotropic, whereas all other meshes were anisotropic. Comparing the structural properties of these meshes, Gynemesh PS and Polyform were the stiffest: 60 % and 42 % stiffer than SmartMesh (p < 0.001) and Novasilk (p < 0.001), respectively. However, no significant differences were found between these two mesh products and UltraPro. CONCLUSIONS: Porosity, anisotropy, and biomechanical behavior of these five commonly used polypropylene mesh products were significantly different. This study provides baseline data for future implantation studies of prolapse mesh products.

THE EFFECT OF PREGNANCY AND POSTPARTUM RECOVERY ON THE VISCOELASTIC BEHAVIOR OF THE RAT CERVIX.

The objective of this study was to elucidate the normal functional adaptations of the cervix in pregnancy. Utilizing a Long-Evans rodent model, the cervix was divided into distal and proximal portions for virgin, mid-pregnant, and four weeks postpartum animals. The quasi-linear viscoelastic theory describes the elastic and viscous behavior of the cervix. A hydroxyproline assay was used to measure collagen content. The nonlinearity of the elastic response significantly increased throughout the entire cervix during pregnancy when compared to virgin samples (p < 0.05) and was similar to virgin samples postpartum. All viscous behavior, except for the short-term relaxation of the proximal cervix, significantly differed for pregnant specimens (p < 0.05) and remained similar to pregnant samples postpartum. Collagen content was found to increase by mid-pregnancy only in the proximal cervix when compared to virgin. Distal and proximal portions, however, were found to differ in collagen content at all time points (p < 0.05). This study finds that the cervix becomes elastically stiffer with increasing strain and exhibits increased viscous behavior during pregnancy, with incomplete recovery postpartum. These alterations allow for quick dissipation of loads, and are likely related to altered matrix organization and porosity reported by others.