An epigenetically distinct HSC subset supports thymic reconstitution.

Hematopoietic stem cells (HSCs) with multilineage potential are critical for effective T cell reconstitution and restoration of the adaptive immune system after allogeneic Hematopoietic Cell Transplantation (allo-HCT). The Kit lo subset of HSCs is enriched for multipotential precursors, 1, 2 but their T-cell lineage potential has not been well-characterized. We therefore studied the thymic reconstituting and T-cell potential of Kit lo HSCs. Using a preclinical allo-HCT model, we demonstrate that Kit lo HSCs support better thymic recovery, and T-cell reconstitution resulting in improved T cell responses to infection post-HCT. Furthermore, Kit lo HSCs with augmented BM lymphopoiesis mitigate age-associated thymic alterations, thus enhancing T-cell recovery in middle-aged hosts. We find the frequency of the Kit lo subset declines with age, providing one explanation for the reduced frequency of T-competent HSCs and reduced T-lymphopoietic potential in BM precursors of aged mice. 3, 4, 5 Chromatin profiling revealed that Kit lo HSCs exhibit higher activity of lymphoid-specifying transcription factors (TFs), including Zbtb1 . Deletion of Zbtb1 in Kit lo HSCs diminished their T-cell potential, while reinstating Zbtb1 in megakaryocytic-biased Kit hi HSCs rescued T-cell potential, in vitro and in vivo . Finally, we discover an analogous Kit lo HSC subset with enhanced lymphoid potential in human bone marrow. Our results demonstrate that Kit lo HSCs with enhanced lymphoid potential have a distinct underlying epigenetic program.

Experimental evolution under predation reduces body size in dung flies but courtship displays persist in males (Diptera: Sepsidae).

Exaggerated sexual traits, such as ornaments and courtship displays, are crucial for mate acquisition in many species and are often subject to directional runaway selection. However, in the face of high predation risk, natural selection can result in a reduction of conspicuous precopulatory displays to avoid detection by potential predators. Sexual selection may then favour increased investment in inconspicuous postcopulatory traits. Here, we investigated the transgenerational effects of predation on precopulatory male courtship and postcopulatory sexual traits (testes size, sperm length) in a dung fly, Sepsis punctum (Sepsidae). Behavioural assays prior to selection document a marked decrease in male courtship displays in the presence of a predator, the Asian Ant Mantis (Odontomantis planiceps). However, after ten generations of experimental evolution, flies exhibited a marked increase in courtship, both in the absence and presence of a predator. Additionally, under sustained predation pressure, male and female body size decreased but male postcopulatory traits were not significantly affected. These results suggest that precopulatory courtship can be under strong sexual selection even in the face of predation pressure. Larger flies were more susceptible to predation, and there could be canalisation of postcopulatory traits that are crucial for fertilisation.

Premature Activation of the HIV-1 Protease Is Influenced by Polymorphisms in the Hinge Region.

HIV-1 protease inhibitors are an essential component of antiretroviral therapy. However, drug resistance is a pervasive issue motivating a persistent search for novel therapies. Recent reports found that when protease activates within the host cell's cytosol, it facilitates the pyroptotic killing of infected cells. This has led to speculation that promoting protease activation, rather than inhibiting it, could help to eradicate infected cells and potentially cure HIV-1 infection. Here, we used a nanoscale flow cytometry-based assay to characterize protease resistance mutations and polymorphisms. We quantified protease activity, viral concentration, and premature protease activation and confirmed previous findings that major resistance mutations generally destabilize the protease structure. Intriguingly, we found evidence that common polymorphisms in the hinge domain of protease can influence its susceptibility to premature activation. This suggests that viral heterogeneity could pose a considerable challenge for therapeutic strategies aimed at inducing premature protease activation in the future.

Efficacy and Safety of WCFA19 (Weissella confusa WIKIM51) in Reducing Body Fat in Overweight and Obese Adults.

Background: WCFA19 (Weissella confusa WIKIM51), found during the fermentation of kimchi, is known for its inhibitory effects on body weight and body fat. This study looked at the impact of WCFA19 isolated from dandelion kimchi on weight loss in overweight and obese adults that are otherwise healthy. Methods: This study was conducted as a multicenter, double-blind, randomized, placebo-controlled study with 104 overweight and obese subjects. Subjects were randomized evenly into the test group (WCFA19, 500 mg, n = 40) or control group (n = 34) for 12 weeks from 14 June 2021 to 24 December 2021. Effects were based on DEXA to measure changes in body fat mass and percentage. Results: Among the 74 subjects analyzed, WCFA19 oral supplementation for 12 weeks resulted in a significant decrease in body fat mass of 633.38 ± 1396.17 g (p = 0.0066) in overweight and obese individuals in the experimental group. The control group showed an increase of 59.10 ± 1120.57 g (p = 0.7604), indicating a statistically significant difference between the two groups. There was also a statistically significant difference (p = 0.0448) in the change in body fat percentage, with a decrease of 0.41 ± 1.22% (p = 0.0424) in the experimental group and an increase of 0.17 ± 1.21% (p = 0.4078) in the control group. No significant adverse events were reported. Conclusions: Oral supplementation of 500 mg of WCFA19 for 12 weeks is associated with a decrease in body weight, particularly in body fat mass and percentage.

Kalium channelrhodopsins effectively inhibit neurons.

The analysis of neural circuits has been revolutionized by optogenetic methods. Light-gated chloride-conducting anion channelrhodopsins (ACRs)-recently emerged as powerful neuron inhibitors. For cells or sub-neuronal compartments with high intracellular chloride concentrations, however, a chloride conductance can have instead an activating effect. The recently discovered light-gated, potassium-conducting, kalium channelrhodopsins (KCRs) might serve as an alternative in these situations, with potentially broad application. As yet, KCRs have not been shown to confer potent inhibitory effects in small genetically tractable animals. Here, we evaluated the utility of KCRs to suppress behavior and inhibit neural activity in Drosophila, Caenorhabditis elegans, and zebrafish. In direct comparisons with ACR1, a KCR1 variant with enhanced plasma-membrane trafficking displayed comparable potency, but with improved properties that include reduced toxicity and superior efficacy in putative high-chloride cells. This comparative analysis of behavioral inhibition between chloride- and potassium-selective silencing tools establishes KCRs as next-generation optogenetic inhibitors for in vivo circuit analysis in behaving animals.

The Role of Human Voice in Direct-To-Consumer Health Communication.

Despite overall positive perceptions, many customers distrust direct-to-consumer genetic testing companies in regard to privacy and aftercare. Prior research suggests companies can assuage mistrust by personalizing communication when discussing sensitive health information. This content analysis of customer e-mails (N = 338) investigates the purpose, personalization, and use of the human voice strategy by direct-to-consumer genetic testing companies to gain trust. Results reveal that companies rarely use human voice when communicating with customers, most of the information provided is promotional, and they invite dialogue less over time. Theoretical and practical implications are provided.

Exploring the personal stroke and rehabilitation experiences of older adults with chronic stroke during the COVID-19 pandemic: a qualitative descriptive study.

PURPOSE: The purpose of this study was to explore the personal stroke and rehabilitation experiences of older adults with chronic stroke living in a mid-sized Northwestern Ontario city in Canada during the COVID-19 pandemic. METHODS: A qualitative descriptive approach with a constructivist worldview was used. In addition, a semi-structured interview guide was used to gather the participants' perspectives on their experiences throughout stroke recovery. Ten participants were interviewed, including six males and four females. The interviews were completed, transcribed, and analysed using inductive and deductive content analysis. Multiple steps were taken to enhance data trustworthiness. RESULTS: Six main themes and eight related subthemes emerged. These included: getting help is complex, the effects of stroke are multifaceted, losing rehabilitation services during the COVID-19 pandemic, overcoming hardships but not alone, "If you don't use it, you lost it": rehabilitative success is based on one's actions, and "look at me now": the importance of taking pride in one's successes. CONCLUSIONS: One unique finding was that the participants used this study as an opportunity to teach and advocate for future stroke survivors which is not often seen in qualitative stroke rehabilitation research. Future stroke research should place emphasis on both the positive and negative experiences of this population.

A pilot study on the "ScoliBrace" in the treatment of adolescent idiopathic scoliosis.

PURPOSE: Bracing for adolescents with idiopathic scoliosis (AIS) is a treatment option to prevent curve progression to surgical level. This study aimed to assess the efficacy of a 3D fully customized over corrective brace, "ScoliBrace," an orthosis treatment for AIS. METHODS: This was a prospective pilot study of AIS female patients with inclusion criteria followed recommended Scoliosis Research Society (SRS) Guidelines. Cobb angles measured at: baseline (T0), 21 months (T5-2), skeletal maturity (T6), 6 months post-brace (T7), along with hours of brace wear using a thermal sensor and health-related quality of life (HRQoL) using the SRS-22r questionnaire. RESULTS: A total of 30 female AIS patients with mean age 11.85 ± 0.68 years, predominantly Risser 0 (70%), and median Cobb angle 29° were recruited; 21 patients were included for the final analysis. Results showed significant difference in Cobb angle between T0 and T5-2 (median = 22.5° vs. 28.5°, p = 0.0082). 57.14% had reduction in Cobb angle by ≥ 5° at skeletal maturity. Cobb angle reduced 0.794° for each additional hour of dosage (p = 0.036, 95% CI = - 1.532°, - 0.056°). Although pain level was increased at T6 (4.37 ± 0.51vs.4.70 ± 0.41, p = 0.014), patients reported significantly greater satisfaction with management of their condition (3.90 ± 0.90vs.3.29 ± 0.88, p = 0.020). CONCLUSION: Results show similar findings to the BRAIST study, whereby curves remained under surgical threshold and showed improvement. More than half had curve reduction of ≥ 5° at skeletal maturity. Increased dose was also associated with improved outcomes. Using "ScoliBrace" as a non-surgical treatment, maintained curves below surgical threshold and showed curve reduction, improving patient satisfaction with management.

Can the Lower Extremity Functional Scale Be Used in Children and Adolescents? A Validation Study.

BACKGROUND: The lower extremity functional scale (LEFS) is a patient-reported outcome measure for assessment of lower extremity function. It has been validated in adults but not in children or adolescents. METHODS: Patients 8 to 18 years of age who were treated for a lower limb fracture, injury, or other conditions were invited to join the study. LEFS and Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL) were administered. Reliability and validity of the LEFS were determined for the entire cohort and for 2 age groups (children: 8 to 12 years; adolescents 13 to 18 years) using PedsQL as comparison. RESULTS: A total of 178 patients were recruited into this study. In the entire cohort, internal consistency of LEFS was excellent (0. 972) with acceptable floor (0%) and ceiling (12%) effects. Correlation between LEFS and PedsQL physical functioning component was high ( r =0.859). Construct validity was acceptable, with all 8 hypotheses demonstrating statistical significance. Factor analysis showed that item 15 (sitting for 1 hour) may contribute to measurement error in the pediatric population. Results remained similar when comparing the 2 age groups. CONCLUSIONS: The LEFS is overall an acceptable patient-reported outcome assessment of children and adolescents with various lower limbs disorders. LEVEL OF EVIDENCE: Level II.

Improved Comfortability and Satisfaction of Hybrid-mesh Casts in the Conservative Management of Pediatric Supracondylar Humeral Fractures: A Randomized Controlled Trial.

BACKGROUND: Cast immobilization is the mainstay of treatment for stable pediatric supracondylar humeral fractures (SCHFs). In recent years, a waterproof and breathable hybrid-mesh (HM) cast has emerged and been marketed to address common complaints such as itch, skin irritation, and malodor. Hence, this randomized controlled trial seeks to assess the overall satisfaction, comfort, and clinical outcomes of using HM casts in the conservative treatment of stable pediatric SCHF. METHODS: Seventy-nine patients (age range: 1 to 10 y) with modified Gartland's classification Type I and Type IIa SCHF were recruited and randomized for immobilization with either fiberglass or HM long-arm cast for 3 weeks. During follow-up visits, patients were assessed for any loss of reduction and skin rash. The weight of casts, the presence of cast breakage, the duration of cast application, and removal were recorded. A self-reported patient comfort and satisfaction questionnaire was also administered during the same visit. RESULTS: The final analysis included 38 patients immobilized with fiberglass casts and 39 patients with HM casts. Despite the significantly longer duration required for HM cast removal (4.18±1.25 min vs. 2.25±0.55 min, P <0.001), the HM cast was significantly lighter than its fiberglass counterpart (162.82±23.94 g vs. 203.95±36.52 g, P <0.001). The HM casts have better comfort (4.05±0.887 vs. 3.47±0.951, P =0.007) and satisfaction (3.69±1.055 vs. 3.11±0.953, P =0.012) scores as compared to fiberglass casts for immobilizing pediatric SCHF without compromising clinical outcome. CONCLUSIONS: HM casts have better comfort and overall satisfaction as compared to conventional fiberglass casts for immobilizing pediatric SCHF without compromising clinical outcomes. LEVEL OF EVIDENCE: Level II-therapeutic studies-investigating the results of treatment.

Developing an innovative pediatric integrated mental health care program: interdisciplinary team successes and challenges.

Introduction: Children and adolescents often do not receive mental healthcare when they need it. By 2021, the complex impact of the COVID-19 pandemic, structural racism, inequality in access to healthcare, and a growing shortage of mental health providers led to a national emergency in child and adolescent mental health in the United States. The need for effective, accessible treatment is more pressing than ever. Interdisciplinary, team-based pediatric integrated mental healthcare has been shown to be efficacious, accessible, and cost-effective. Methods: In response to the youth mental health crisis, Rady Children's Hospital-San Diego's Transforming Mental Health Initiative aimed to increase early identification of mental illness and improve access to effective treatment for children and adolescents. A stakeholder engagement process was established with affiliated pediatric clinics, community mental health organizations, and existing pediatric integrated care programs, leading to the development of the Primary Care Mental Health Integration program and drawing from established models of integrated care: Primary Care Behavioral Health and Collaborative Care. Results: As of 2023, the Primary Care Mental Health Integration program established integrated care teams in 10 primary care clinics across San Diego and Riverside counties in California. Measurement-based care has been implemented and preliminary results indicate that patient response to therapy has resulted in a 44% reduction in anxiety symptoms and a 62% decrease in depression symptoms. The program works toward fiscal sustainability via fee-for-service reimbursement and more comprehensive payor contracts. The impact on patients, primary care provider satisfaction, measurement-based care, funding strategies, as well as challenges faced and changes made will be discussed using the lens of the Reach, Effectiveness, Adoption, Implementation and Maintenance framework. Discussion: Preliminary results suggest that the Primary Care Mental Health Integration is a highly collaborative integrated care model that identifies the needs of children and adolescents and delivers brief, evidence informed treatment. The successful integration of this model into 10 primary care clinics over 3 years has laid the groundwork for future program expansion. This model of care can play a role addressing youth mental health and increasing access to care. Challenges, successes, and lessons learned will be reviewed.

An international RAND/UCLA expert panel to determine the optimal diagnosis and management of burn inhalation injury.

BACKGROUND: Burn inhalation injury (BII) is a major cause of burn-related mortality and morbidity. Despite published practice guidelines, no consensus exists for the best strategies regarding diagnosis and management of BII. A modified DELPHI study using the RAND/UCLA (University of California, Los Angeles) Appropriateness Method (RAM) systematically analysed the opinions of an expert panel. Expert opinion was combined with available evidence to determine what constitutes appropriate and inappropriate judgement in the diagnosis and management of BII. METHODS: A 15-person multidisciplinary panel comprised anaesthetists, intensivists and plastic surgeons involved in the clinical management of major burn patients adopted a modified Delphi approach using the RAM method. They rated the appropriateness of statements describing diagnostic and management options for BII on a Likert scale. A modified final survey comprising 140 statements was completed, subdivided into history and physical examination (20), investigations (39), airway management (5), systemic toxicity (23), invasive mechanical ventilation (29) and pharmacotherapy (24). Median appropriateness ratings and the disagreement index (DI) were calculated to classify statements as appropriate, uncertain, or inappropriate. RESULTS: Of 140 statements, 74 were rated as appropriate, 40 as uncertain and 26 as inappropriate. Initial intubation with ≥ 8.0 mm endotracheal tubes, lung protective ventilatory strategies, initial bronchoscopic lavage, serial bronchoscopic lavage for severe BII, nebulised heparin and salbutamol administration for moderate-severe BII and N-acetylcysteine for moderate BII were rated appropriate. Non-protective ventilatory strategies, high-frequency oscillatory ventilation, high-frequency percussive ventilation, prophylactic systemic antibiotics and corticosteroids were rated inappropriate. Experts disagreed (DI ≥ 1) on six statements, classified uncertain: the use of flexible fiberoptic bronchoscopy to guide fluid requirements (DI = 1.52), intubation with endotracheal tubes of internal diameter < 8.0 mm (DI = 1.19), use of airway pressure release ventilation modality (DI = 1.19) and nebulised 5000IU heparin, N-acetylcysteine and salbutamol for mild BII (DI = 1.52, 1.70, 1.36, respectively). CONCLUSIONS: Burns experts mostly agreed on appropriate and inappropriate diagnostic and management criteria of BII as in published guidance. Uncertainty exists as to the optimal diagnosis and management of differing grades of severity of BII. Future research should investigate the accuracy of bronchoscopic grading of BII, the value of bronchial lavage in differing severity groups and the effectiveness of nebulised therapies in different severities of BII.

Use of cryotherapy in the postoperative management of paediatric anterior cruciate ligament reconstruction: a prospective randomised controlled trial.

To investigate the efficacy of cryotherapy in relieving postoperative pain and restoring knee range-of-motion (ROM) after paediatric anterior cruciate ligament reconstruction (ACLR). Patients undergoing primary ACLR were randomised into cryotherapy or non-cryotherapy groups. Those receiving cryotherapy were subjected to a standardised icing protocol. Icing schedules were used to assess compliance. Standard postoperative rehabilitation protocol was followed for both groups. Outcome measurements were visual analogue scale at rest and movement and knee ROM. Patients were assessed on postoperative day 1 (POD1), 1, 4 and 6 weeks. Twenty-one out of 42 patients received cryotherapy. Both groups were similar in demographics, surgical technique and use of intraoperative anaesthesia. Patients in the cryotherapy group reported lower overall mean pain scores throughout the study duration at rest (0.61 ±â€…1.70, 95% CI = 0.23-0.99 vs. 1.06 ±â€…2.03, 95% CI = 0.60-1.53) and on movement (2.19 ±â€…2.68, 95% CI = 1.59-2.79 vs. 3.13 ±â€…2.75, 95% CI = 2.51-3.75; P = 0.032). Knee flexion in the cryotherapy group showed better recovery of knee flexion from week 4 onwards. Improvement of knee flexion from POD1 is statistically significant at week 6 (98.7 ±â€…19.1°, 95% CI = 89.5-107.9 vs. 65.4 ±â€…49.9°, 95% CI = 42.7-88.1; P = 0.010) and overall mean (71.2 ±â€…35.9°, 95% CI = 61.2-81.1 vs. 45.3 ±â€…55.5°, 95% CI = 30.4-60.2; P = 0.005). The cryotherapy group reported statistically significant better degree of overall mean knee extension (1.2 ±â€…3.3°, 95% CI = 0.5-2.0 vs. 2.6 ±â€…4.6°, 95% CI = 1.6-3.7; P = 0.032). The use of cryotherapy in postoperative ACLR recovery in paediatrics is a simple yet effective measure resulting in short-term pain relief and improvement in knee flexion.

How well do we assess the adequacy of bending films in scoliosis?

Aims: To determine whether side-bending films in scoliosis are assessed for adequacy in clinical practice; and to introduce a novel method for doing so. Methods: Six surgeons and eight radiographers were invited to participate in four online surveys. The generic survey comprised erect and left and right bending radiographs of eight individuals with scoliosis, with an average age of 14.6 years. Respondents were asked to indicate whether each bending film was optimal (adequate) or suboptimal. In the first survey, they were also asked if they currently assessed the adequacy of bending films. A similar second survey was sent out two weeks later, using the same eight cases but in a different order. In the third survey, a guide for assessing bending film adequacy was attached along with the radiographs to introduce the novel T1-45B method, in which the upper endplate of T1 must tilt ≥ 45° from baseline for the study to be considered optimal. A fourth and final survey was subsequently conducted for confirmation. Results: Overall, 12 (86%) of 14 respondents did not use any criteria to assess the bending film adequacy; the remaining two each described a different invalidated method. In total, 12 (86%) of the respondents felt T1-45B was easy to learn and apply. There was fair to substantial intra-rater reliability (k = 0.25 to 0.88) which improved to fair to almost perfect (k = 0.38 to 0.88) post-introduction of the guide. Inter-rater reliability varied considerably among the rater groups but similarly increased following introduction of the guide (kS1 = 0.19 to 0.34, kS2 = 0.33 to 0.43 vs kS3 = 0.49 to 0.5, kS4 = 0.35 to 0.43). Conclusion: Many surgeons and radiographers do not assess spinal bending films for adequacy. We propose that the change in the plane of the upper endplate of T1 on side-bending can be used in this evaluation. In the T1-45B method, a change of ≥ 45° on side bending qualifies as an adequate bend effort.

Tissue-specific features of the T cell repertoire after allogeneic hematopoietic cell transplantation in human and mouse.

T cells are the central drivers of many inflammatory diseases, but the repertoire of tissue-resident T cells at sites of pathology in human organs remains poorly understood. We examined the site-specificity of T cell receptor (TCR) repertoires across tissues (5 to 18 tissues per patient) in prospectively collected autopsies of patients with and without graft-versus-host disease (GVHD), a potentially lethal tissue-targeting complication of allogeneic hematopoietic cell transplantation, and in mouse models of GVHD. Anatomic similarity between tissues was a key determinant of TCR repertoire composition within patients, independent of disease or transplant status. The T cells recovered from peripheral blood and spleens in patients and mice captured a limited portion of the TCR repertoire detected in tissues. Whereas few T cell clones were shared across patients, motif-based clustering revealed shared repertoire signatures across patients in a tissue-specific fashion. T cells at disease sites had a tissue-resident phenotype and were of donor origin based on single-cell chimerism analysis. These data demonstrate the complex composition of T cell populations that persist in human tissues at the end stage of an inflammatory disorder after lymphocyte-directed therapy. These findings also underscore the importance of studying T cell in tissues rather than blood for tissue-based pathologies and suggest the tissue-specific nature of both the endogenous and posttransplant T cell landscape.

The machine-vision image guided surgery system reduces fluoroscopy time, ionizing radiation and intraoperative blood loss in posterior spinal fusion for scoliosis.

PURPOSE: To determine if the novel 3D Machine-Vision Image Guided Surgery (MvIGS) (FLASH™) system can reduce intraoperative radiation exposure, while improving surgical outcomes when compared to 2D fluoroscopic navigation. METHODS: Clinical and radiographic records of 128 patients (≤ 18 years of age) who underwent posterior spinal fusion (PSF), utilising either MvIGS or 2D fluoroscopy, for severe idiopathic scoliosis were retrospectively reviewed. Operative time was analysed using the cumulative sum (CUSUM) method to evaluate the learning curve for MvIGS. RESULTS: Between 2017 and 2021, 64 patients underwent PSF using pedicle screws with 2D fluoroscopy and another 64 with the MvIGS. Age, gender, BMI, and scoliosis aetiology were comparable between the two groups. The CUSUM method estimated that the MvIGS learning curve with respect to operative time was 9 cases. This curve consisted of 2 phases: Phase 1 comprises the first 9 cases and Phase 2 the remaining 55 cases. Compared to 2D fluoroscopy, MvIGS reduced intraoperative fluoroscopy time, radiation exposure, estimated blood loss and length of stay by 53%, 62% 44%, and 21% respectively. Scoliosis curve correction was 4% higher in the MvIGS group, without any increase in operative time. CONCLUSION: MvIGS for screw insertion in PSF contributed to a significant reduction in intraoperative radiation exposure and fluoroscopy time, as well as blood loss and length of stay. The real-time feedback and ability to visualize the pedicle in 3D with MvIGS enabled greater curve correction without increasing the operative time.

Gunther Tulip Filter Strut Penetration: Benign Long-Term Follow-up.

PURPOSE: To describe the natural history of Gunther Tulip filter (GTF) strut penetration based on the computed tomography (CT)-documented distance penetrated over time and any clinical manifestations. MATERIALS AND METHODS: The records of 203 patients (mean age, 59.1 years; 59.4% men) who had had an infrarenal GTF placed for venous thromboembolism (84.2%) with contraindications to anticoagulation (95.1%) and had CT follow-up were reviewed retrospectively for clinical or imaging evidence of complications. Filter strut penetration was measured on axial images from the outer caval wall to the inner edge of the distal end of each strut. Filter strut behavior over time was modeled using a linear mixed model. RESULTS: The extent of penetration correlated positively with filter dwell time (P < .001) but plateaued at 3.3 mm at 10-year follow-up. At median 4.7-year follow-up 79.3% of patients had at least 1 strut that was >0.2 mm and 31% had a strut >3 mm from the inferior vena caval wall. The extent of strut penetration was greater at all time points for women (P = .002). Abutment or entry into an adjacent structure was identified in 183 struts of 105 (52.7%) filters; of the 80 filters with CT follow-up, 47% showed progression and 19% regressed. There were no symptoms referable to filter strut penetration. CONCLUSIONS: GTF struts often penetrate the inferior vena cava progressively; however, this tends to plateau by 10 years. The limited long-term progression and a very low incidence of symptomatic complications together support a noninterventional approach to the finding of an asymptomatic GTF strut penetration.

Study protocol of the Our Futures Vaping Trial: a cluster randomised controlled trial of a school-based eHealth intervention to prevent e-cigarette use among adolescents.

BACKGROUND: Effective and scalable prevention approaches are urgently needed to address the rapidly increasing rates of e-cigarette use among adolescents. School-based eHealth interventions can be an efficient, effective, and economical approach, yet there are none targeting e-cigarettes within Australia. This paper describes the protocol of the OurFutures Vaping Trial which aims to evaluate the efficacy and cost-effectiveness of the first school-based eHealth intervention targeting e-cigarettes in Australia. METHODS: A two-arm cluster randomised controlled trial will be conducted among Year 7 and 8 students (aged 12-14 years) in 42 secondary schools across New South Wales, Western Australia and Queensland, Australia. Using stratified block randomisation, schools will be assigned to either the OurFutures Vaping Program intervention group or an active control group (health education as usual). The intervention consists of four web-based cartoon lessons and accompanying activities delivered during health education over a four-week period. Whilst primarily focused on e-cigarette use, the program simultaneously addresses tobacco cigarette use. Students will complete online self-report surveys at baseline, post-intervention, 6-, 12-, 24-, and 36-months after baseline. The primary outcome is the uptake of e-cigarette use at 12-month follow-up. Secondary outcomes include the uptake of tobacco smoking, frequency/quantity of e-cigarettes use and tobacco smoking, intentions to use e-cigarettes/tobacco cigarettes, knowledge about e-cigarettes/tobacco cigarettes, motives and attitudes relating to e-cigarettes, self-efficacy to resist peer pressure and refuse e-cigarettes, mental health, quality of life, and resource utilisation. Generalized mixed effects regression will investigate whether receiving the intervention reduces the likelihood of primary and secondary outcomes. Cost-effectiveness and the effect on primary and secondary outcomes will also be examined over the longer-term. DISCUSSION: If effective, the intervention will be readily accessible to schools via the OurFutures platform and has the potential to make substantial health and economic impact. Without such intervention, young Australians will be the first generation to use nicotine at higher rates than previous generations, thereby undoing decades of effective tobacco control. TRIAL REGISTRATION: The trial has been prospectively registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12623000022662; date registered: 10/01/2023).