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Neha Durgam,1 Triza Brion,1 Hannah B Lewis,1 Biba Tinga,2 Wilson Sanon,3 Mark Lundie,4 Chantal Cadieux4 1ICON Plc, Raleigh, NC, USA; 2Sickle Cell Disease Association of Canada (SCDAC), Toronto, ON, Canada; 3Association d’Anémie Falciforme du Québec, Montreal, Quebec, Canada; 4Pfizer Canada ULC, Kirkland, Quebec, CanadaCorrespondence: Neha Durgam, 4130 Parklake Ave, Suite 400, Raleigh, NC, 27612, USA, Tel +1 267 827 7447, Email Neha.Durgam@iconplc.com; nehadurgam@gmail.comPurpose: There is little research on care-seeking preferences during active pain crises for sickle cell disease (SCD) patients and their caregivers. The objective of this study was to identify relevant, patient or caregiver narratives of the pain crisis experience, to understand the factors that contribute to care-seeking during a pain crisis, and to identify preferences when making care-seeking decisions during a pain crisis.Patients and Methods: Qualitative semi-structured interviews were conducted with Canadian residents with a self-reported SCD diagnosis, who were either ≥ 18 years of age or an adolescent between the ages of 12– 18. Interviews were hosted virtually, audio-recorded, and transcribed verbatim.Results: A total of 23 individuals participated (74% female; 26% male), including six adolescents with parent dyads and 11 adults. Almost all (N = 21, 91.3%) participants were Black/African American. Participants mentioned many factors that influenced care-seeking decisions, mainly the symptom and pain experience; institutional factors (waiting time, the presence of and adherence to treatment guidelines, and the empathy or racial bias felt from medical staff); and subject-level factors (age and a flexibility in daily responsibilities).Conclusion: This study identified important institutional and subject-level considerations involved in care-seeking decisions. Most importantly, this study highlights the racial stigma faced by many patients when care-seeking in the ER and the lack of care protocol implemented, which hinders care-seeking in a dedicated medical facility. From the patient perspective, these are clear gaps to fill to encourage patients to seek and receive the care they deserve.Keywords: vaso-occlusive crisis, sickle cell disease, pain crisis, care-seeking, standard of care

PRE ACT is an EU funded project that aims to predict the risk of radiotherapy side effects, including arm lymphedema in breast cancer patients based on 4 multicenter international studies CANTO, HYPOG-01 and REQUITE. Because of inter-investigators variability and clinical practice diversity across different centers and cohorts, manual contours are not homogeneous enough to extract necessary features to train the predictive model. The aim of this study is to conduct qualitative and comparative evaluation of the automatic and manual contours to showcase the reliability of the former. We have generated Organ-at-Risk (OAR) contours with Annotate module from ART-Plan (from TheraPanacea) for six crucial OARs for dose planning of breast cancer loco regional radiotherapy, i.e. esophagus, thyroid, heart, ipsilateral lung, ipsilateral humeral head and contralateral breast. For this evaluation, four independent international radiation oncologists have been presented blindly with both automatic and manual contours from a randomly selected subset of left and right breast cancer patients from the PRE ACT dataset (7052 patients). 10 automatic and manual cases were presented across two sessions, with a washout of a minimum of 48 hours. Rating of the contours followed an A-B-C grid, with A for satisfactory contours, B requiring minor changes, and C needing major changes or redoing. A and B contours were estimated as acceptable, therefore ratings of A and B contours define the acceptance rate for each organ. Average qualitative evaluations are presented in table 1. Automatic contours acceptance ranges from 92 to 100%, whilst manual contours acceptance ranges from 72% to 100%. Inter-expert agreement varies a lot across organs. The lowest inter-expert agreement was obtained for humeral head and heart (45 % for both) for automatic contours and thyroid for manual contours (38,3%). The highest inter-expert agreement was for esophagus and left breast (68.3%) for automatic contours and left breast for manual contours (66.7%). These values are averaged across 4 experts. With this study, we demonstrate that automatic contouring is an excellent and reliable tool to obtain segmentation of OARs with a robust a homogeneous clinical acceptability across diverse cohorts, with many applications to clinical trials. [ABSTRACT FROM AUTHOR]

The dataset presented contains the experimental structural response, in the frequency domain, of a suspended steel plate to a point force excitation. The plate is excited by a mechanical point force generated by a Brüel & kJær shaker with a white noise signal input from 3.125 Hz to 2000 Hz. The out-of-plate displacement fields on a 2D grid were measured using a Polytec PSV-400 Scanning Vibrometer. Finally, the displacement fields are acquired by a Fourier analyser connected to a sampler. The dataset provided is a useful resource for researchers to study the structural dynamic behaviour of large thin plates in the frequency domain and to validate the effectiveness of wavenumber identification methods. Its value has been illustrated in the research paper "Algebraic K-Space Identification 2D technique for the automatic extraction of complex k-space of 2D structures in presence of uncertainty" [1]. The data collection was carried out during three weeks in April 2022 at the Ecole Central de Lyon., (© 2024 The Author(s).)

Background: Due to wide-ranging impacts of Ulcerative Colitis (UC), regulatory authorities emphasize the importance of including validated patient-reported symptom severity measures in clinical trials., Aim: To describe the development and validation of the Ulcerative Colitis-Symptom Questionnaire (UC-SQ)., Methods: The UC-SQ was developed in a qualitative study involving a targeted literature review, semi-structured concept elicitation interviews, and combined concept elicitation/cognitive interviews. Measurement properties, including item-level analyses, factor structure, reliability, validity, responsiveness, and clinically meaningful change were evaluated using data from a phase 2b, randomized trial in adults with UC (N = 113)., Results: Fourteen symptom concepts were elicited across 22 interviews, with saturation at the fifth interview. Twenty-two items were unmodified as cognitive interview participants interpreted underlying concepts correctly. Instructions were clear and items were relevant, with appropriate response options and recall periods. Reduction to 17 items was completed prior to psychometric testing. Two items (joint pain/constipation) did not contribute to reliability in initial testing and were included as non-scored items. The 15-item UC-SQ showed evidence of internal consistency (α = 0.86) and test-retest reliability (intraclass correlation coefficient = 0.88). The UC-SQ discriminated by disease severity as defined by Mayo and Inflammatory Bowel Disease Questionnaire scores (p < 0.0001). Convergent validity was supported by strong correlations with criterion measures. The UC-SQ was responsive in patients indicating change in other measures. A 10-point decrease from baseline indicated within-patient meaningful improvement., Conclusions: The UC-SQ is reliable, valid and responsive, with a 10-point improvement estimating within-patient clinically meaningful improvement. The tool is fit-for-purpose as a key endpoint in pivotal UC trials., (© 2023. The Author(s).)

Objective: To identify in-depth information directly from patients with diabetic foot ulcers (DFU) on DFU symptoms, impacts on functioning and effects on health-related quality of life (HRQoL)., Method: Semi-structured, qualitative concept elicitation interviews were conducted with patients with DFUs (Wagner grade 1 or 2) until saturation was reached. Qualitative analysis (using MAXQDA, VERBI GmbH, Germany) of interview transcripts was conducted to identify concepts relevant to patients with DFUs, based on the frequency of mentions, and elucidate themes regarding impacts on HRQoL., Results: Of the 18 participants, most were male (n=14; 78%) and 10 (56%) presented with a Wagner grade of 1. Frequently reported symptoms were pain/discomfort (n=15; 83%), weeping/discharge (n=10; 56%), bleeding (n=10; 56%) and swelling (n=8; 44%). Overall, patients reported more impacts than symptoms-wound care/treatment burden (n=14; 78%), limitations on exercise/physical activity (n=13; 72%), mobility limitations (n=12; 67%), and offloading (n=12; 67%) were the most frequently mentioned. Based on findings from the patient interviews, a draft conceptual model was developed outlining interrelationships between DFU symptoms, impacts, and HRQoL from the patient perspective., Conclusion: Qualitative interviews captured the breadth of disease-related concepts of direct importance to patients. The draft conceptual model developed from the analysis can help identify measures or instruments for use in assessing patient-reported symptoms or HRQoL in clinical practice and may have wider research applicability, including evaluation of treatment benefits in patients with DFUs.

Osteoarthritis (OA) is a chronic condition characterized by pain during joint movement. Additionally, patients with advanced disease experience pain at rest (ie, ongoing pain) that is generally resistant to nonsteroidal antiinflammatory drugs. Injection of monosodium iodoacetate (MIA) into the intraarticular space of the rodent knee is a well-established model of OA that elicits weight-bearing asymmetry and referred tactile and thermal hypersensitivity. Whether ongoing pain is present in this model is unknown. Additionally, the possible relationship of ongoing pain to MIA dose is not known. MIA produced weight asymmetry, joint osteolysis, and cartilage erosion across a range of doses (1, 3, and 4.8 mg). However, only rats treated with the highest dose of MIA showed conditioned place preference to a context paired with intraarticular lidocaine, indicating relief from ongoing pain. Diclofenac blocked the MIA-induced weight asymmetry but failed to block MIA-induced ongoing pain. Systemic AMG9810, a transient receptor potential V1 channel (TRPV1) antagonist, effectively blocked thermal hypersensitivity, but failed to block high-dose MIA-induced weight asymmetry or ongoing pain. Additionally, systemic or intraarticular HC030031, a TRPA1 antagonist, failed to block high-dose MIA-induced weight asymmetry or ongoing pain. Our studies suggest that a high dose of intraarticular MIA induces ongoing pain originating from the site of injury that is dependent on afferent fiber activity but apparently independent of TRPV1 or TRPA1 activation. Identification of mechanisms driving ongoing pain may enable development of improved treatments for patients with severe OA pain and diminish the need for joint replacement surgery., (Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

A predominant complaint in patients with neuropathic pain is spontaneous pain, often described as burning. Recent studies have demonstrated that negative reinforcement can be used to unmask spontaneous neuropathic pain, allowing for mechanistic investigations. Here, ascending pathways that might contribute to evoked and spontaneous components of an experimental neuropathic pain model were explored. Desensitization of TRPV1-positive fibers with systemic resiniferatoxin (RTX) abolished spinal nerve ligation (SNL) injury-induced thermal hypersensitivity and spontaneous pain, but had no effect on tactile hypersensitivity. Ablation of spinal NK-1 receptor-expressing neurons blocked SNL-induced thermal and tactile hypersensitivity as well as spontaneous pain. After nerve injury, upregulation of neuropeptide Y (NPY) is observed almost exclusively in large-diameter fibers, and inactivation of the brainstem target of these fibers in the nucleus gracilis prevents tactile but not thermal hypersensitivity. Blockade of NPY signaling within the nucleus gracilis failed to block SNL-induced spontaneous pain or thermal hyperalgesia while fully reversing tactile hypersensitivity. Moreover, microinjection of NPY into nucleus gracilis produced robust tactile hypersensitivity, but failed to induce conditioned place aversion. These data suggest that spontaneous neuropathic pain and thermal hyperalgesia are mediated by TRPV1-positive fibers and spinal NK-1-positive ascending projections. In contrast, the large-diameter dorsal column projection can mediate nerve injury-induced tactile hypersensitivity, but does not contribute to spontaneous pain. Because inhibition of tactile hypersensitivity can be achieved either by spinal manipulations or by inactivation of signaling within the nucleus gracilis, the enhanced paw withdrawal response evoked by tactile stimulation does not necessarily reflect allodynia., (Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)