Blinded Review Research Articles

Proceedings of the 2024 Australasian Road Safety Conference - Hobart, Tasmania, Australia

Proceedings of the 2024 annual Australasian Road Safety Conference held in Hobart, Tasmania, Australia. The proceedings provide the Extended Abstracts and Posters describing research, educational and policing program implementation and policy and management strategies related to all aspects of road safety and especially related to the conference theme of Target 2030: What's the pathway forward? Almost 600 delegates from 20 countries attended the face-to-face conference. Authors of accepted Extended Abstracts represented international and local institutions from all aspects of their respective communities including research centres, private companies, government agencies and community groups. These Extended Abstracts provide an indication of the important work being done in Australia, New Zealand and internationally as part of the United Nations, One UN Vision for Road Safety to reduce the number of crashes on the road by 50 percent by 2030. Almost 200 Extended Abstract manuscripts were accepted for long, short and poster sessions. Each Extended Abstract was peer-reviewed by two experts with relevant expertise. Authors were also provided the option of submitting a Full Paper. Those authors who chose to submit a Full Paper for consideration in the Journal of Road Safety (JRS) could do so based on the outcome of the peer review of their Extended Abstract. Submitted Full Papers undergo peer-review by three independent experts matched by their sector. The matching pairs academic authors iwth academic reviewers and practitioner authors with practitioner reivewers. Inclusion in the JRS follows acceptance by the peer-reviewers.The conference covered a comprehensive range of topics including speed, infrastructure and road design, cyclist safety, motorcyclist safety, pedestrian safety, road safety education, licensing, vehicle design, impairment due to distraction from mobile phones, alcohol, drugs as well as the impacts of climate change on future transport systems road safety, road safety issues for Indigenous people groups across New Zealand and Australia, integrating road safety into local Government, automated enforcement, gig economy road safety, older drivers, etc.

A human model of Buruli ulcer: Provisional protocol for a Mycobacterium ulcerans controlled human infection study.

Critical knowledge gaps have impeded progress towards reducing the global burden of disease due to Mycobacterium ulcerans, the cause of the neglected tropical disease Buruli ulcer (BU). Development of a controlled human infection model of BU has been proposed as an experimental platform to explore host-pathogen interactions and evaluate tools for prevention, diagnosis, and treatment. We have previously introduced the use case for a new human model and identified M. ulcerans JKD8049 as a suitable challenge strain. Here, we present a provisional protocol for an initial study, for transparent peer review during the earliest stages of protocol development. Following simultaneous scientific peer review and community/stakeholder consultation of this provisional protocol, we aim to present a refined protocol for institutional review board (IRB) evaluation.

Blinded independent central review versus local investigator assessment of PFS in RCTs of immunotherapy in advanced cancers: A systematic review and meta-analysis

BackgroundAssessment of Progression-free survival (PFS) events by investigators might be inaccurate in randomized controlled trials (RCTs) with open-label design. We explored differences in PFS evaluated by blinded independent central review (BICR) or local investigator assessment (IA) in trials testing immunotherapy (IO) in advanced cancers. MethodsWe systematically reviewed articles of RCTs investigating IO in advanced tumors, published in PubMed-indexed journals up to December 2023. For each RCT, we collected PFS results by BICR and by local IA. We calculated the discrepancy index (DI) as the ratio of BICR and IA Hazard Ratios (HRBICR/HRIA) for PFS. An overall DI and relative confidence interval (CI) were calculated using a fixed-effect model weighted for the inverse of variance. FindingsOnly 32/140 (22.9 %) RCTs reported both BICR and local IA PFS data, including 17,054 patients. PFS was the sole primary endpoint in 19/32 (59.4 %) and a co-primary endpoint 9/32 (28.2 %) trials. The study design was open label or double-blind in 17/32 (53.1 %) and 15/32 (46.9 %) RCTs, respectively. The overall DI was 1.07 (95 % CI 1.01–1.13; I2 =0, p = 0.02), revealing a more optimistic analysis of results in favor of local IA. In the 17 open-label trials, the overall DI was 1.09 (95 % CI 1.02–1.17, I2 =0, p = 0.02), revealing a more favorable interpretation of PFS results by local investigators. InterpretationWe found a statistically significant difference between BICR and local IA of PFS in trials of IO in cancer. These results suggest that the double assessment is recommended in RCTs testing IO, especially in open-label trials. FundingThis work was supported by the MFAG27826–2022 grant (Dr. Alberto Servetto).

Using authentic student personas to inform academic policy review with the lived experience of students: a case study from Nottingham Trent University

ABSTRACT This case study from Nottingham Trent University describes how an intra-departmental collaborative team used the lived experience of students to inform academic policy review. Drawing on data from Student 2025, a longitudinal study exploring the complexity of student experiences and identities, the team created authentic student personas called Student Voice Profiles and supported colleagues to use them in a pilot workshop to consider academic policy and policy changes. Findings were mixed: the pilot project highlighted areas for further development, including improvements to resources; it also generated considerable interest in the potential application of student personas to a range of teaching and learning enhancements, and demonstrated the value of cross-team collaborative working.

Optimalisasi Pemanfaatan Media Pembelajaran Berbasis TikTok sebagai Upaya Meningkatkan Hasil Belajar Siswa

As technology evolves, social media platforms like TikTok have started to be utilized in education as interactive and engaging tools. The aim of this research is to explore the potential of TikTok as a learning medium to improve student learning outcomes. This study uses a literature review method to analyze various sources related to the use of TikTok in education. Data were collected from five academic journal articles and literature reviews that discuss the use of TikTok in different educational contexts. The data analysis technique used in this study is content analysis, which identifies key themes from the related articles and examines the relationship between TikTok usage and student learning outcomes. The research results show that TikTok can enhance student engagement and motivation in learning and have a positive impact on their learning outcomes. TikTok has the ability to present educational material innovatively and effectively by utilizing an appealing visual format. If used correctly, TikTok can become a valuable learning medium. Thus, TikTok offers teachers the opportunity to create more creative and engaging lessons.

Bidirectional association of sleep disorders with chronic kidney disease: a systematic review and meta-analysis

Abstract Background Published studies have suggested a link between chronic kidney disease (CKD) and sleep disorders, although the exact nature of this association has not been uniformly described. Clarifying this relationship may facilitate evidence-based interventions that address the interplay between these disease entities. Such interventions could prevent OSA from worsening CKD and improve the quality of life for CKD patients by reducing the risk of developing OSA. Therefore, the objective of this meta-analysis is to assess the bidirectional association between sleep disorders and CKD. Methods Following a PROSPERO-registered protocol, three blinded reviewers conducted a systematic review of the Medline/PubMed, Embase, Cochrane Library and CINAHL databases for observational studies pertaining to the relationship between sleep disorders and CKD. A meta-analysis was conducted in risk ratios. Results From 63 studies (26 777 524 patients), obstructive sleep apnea (OSA) (RR, 1.68; 95% CI, 1.45 to 1.93), albuminuria (RR, 1.54; 95% CI, 1.18 to 1.99), restless leg syndrome (RLS) (RR, 1.88; 95% CI, 1.48 to 2.38) and insomnia (RR, 1.24; 95% CI, 1.01 to 1.54) were significantly associated with CKD. There was a significant association between OSA (RR, 1.77; 95% CI, 1.56 to 2.01) with incident CKD. There was a significant association of OSA (RR, 1.74; 95% CI, 1.55 to 1.96), RLS (RR, 1.73; 95% CI, 1.32 to 2.25) and insomnia (RR, 1.14; 95% CI, 1.03 to 1.27) in patients with CKD compared with healthy controls. CKD was also significantly associated with incident OSA (RR, 1.60; 95% CI, 1.35 to 1.89). Conclusion The bidirectional associations of obstructive sleep apnea with CKD remained consistent across different stages of CKD, modes of diagnosis of sleep disorder, and geographical region. A bidirectional association was observed between CKD and obstructive sleep apnea, RLS and insomnia. The treatment of sleep disorders may reduce the risk of CKD, and vice versa.

Role of low-impact-factor journals in conservation implementation.

Academic review, promotion, and tenure processes place a premium on frequent publication in high-impact factor (IF) journals. However, conservation often relies on species-specific information that is unlikely to have the broad appeal needed for high-IF journals. Instead, this information is often distributed in low-IF, taxa- and region-specific journals. This suggests a potential mismatch between the incentives for academic researchers and the scientific needs of conservation implementation. To explore this mismatch, we looked at federal implementation of the United States Endangered Species Act (ESA), which requires the use of the "best available science" to list a species as endangered or threatened and thus receive powerful legal protections. In assessing the relationship between academic sources of this "best available science" and ESA implementation, we looked at the 13,292 sources (e.g., academic journals, books, reports, regulations, personal communications, etc.) cited by the second Obama administration (2012-2016) across all ESA listings. We compared the IFs of all 4836 journals that published peer-reviewed papers cited in these listings against their citation frequency in ESA listings to determine whether a journal's IF varied in proportion with its contribution to federal conservation. Most of the peer-reviewed academic articles referenced in ESA listings came from low-IF or no-IF journals that tended to focus on specific taxa or regions. Although we support continued attention to cutting-edge, multidisciplinary science for its ability to chart new pathways and paradigms, our findings stress the need to value and fund the taxa- and region-specific science that underpins actionable conservation laws.

Facial trauma education in radiology: using surgeon feedback as the benchmark for success.

Interpreting CT studies of facial trauma is challenging, and there are often substantial differences in the characterization of complex facial trauma between radiologists and surgeons. We designed a collaborative multidisciplinary project to reconcile differences in facial fracture interpretation through an educational intervention. The effectiveness of this intervention was evaluated through surgeon feedback on radiology reports. Radiology residents, neuroradiology fellows, and neuroradiology attendings were recruited as participants at a single tertiary care academic center. Otolaryngology residents were recruited as evaluators. Participants completed surveys and provided preliminary reports for example cases of facial trauma before and after attending an educational session. Evaluators performed a blinded review of these preliminary reports based on ideal reports developed by surgical and neuroradiology attendings. 26 participants (20 residents, 1 neuroradiology fellow, 5 neuroradiology attendings) completed the study. Six otolaryngology residents participated as evaluators. To assess interrater reliability, three evaluators graded a shared set of 15 reports and demonstrated substantial agreement with a Kendall's W of 0.71. Participants demonstrated significant improvement in overall report accuracy, clarity, and organization. In subunit analysis, there were significant improvements in reporting Le Fort, nasoseptal, and nasoorbitoethmoid fractures. No significant improvements occurred in the reporting of upper face, zygomaticomaxillary complex, or mandibular fractures. In contrast, survey analysis demonstrated significantly improved confidence in interpreting trauma involving all facial subunits. Compared with survey results, surgeon assessment of radiology reports better demonstrated areas of improvement after an educational intervention. A multidisciplinary approach to assessing educational efforts may better evaluate the practical effectiveness of educational interventions.

The diagnostic performance of neck ultrasound in follow-up of advanced stage differentiated thyroid cancer

BackgroundDifferentiated thyroid cancer (DTC) requires long-term follow-up due to the risk of delayed recurrence. Follow-up surveillance involves serial neck ultrasound (US) and thyroglobulin (Tg); however, the optimal frequency and diagnostic performance of neck US outside of specialized thyroid cancer centres in higher risk patients is not well defined. We sought to evaluate the diagnostic performance of US and serial Tg in advanced stage DTC.MethodsWe retrospectively reviewed our thyroid cancer database for patients with stage III and IV DTC from 2006 to 2018, total thyroidectomy, and at least 2 years follow-up to assess recurrence rates. Those with hemi-thyroidectomy or anti-Tg antibodies were excluded. Diagnostic performance of US and Tg were assessed using a composite reference standard of follow-up imaging and pathology. All relevant US were reviewed by a blinded expert radiologist for uniformity.ResultsOf 136 included patients (91 females, mean age 58.9), 26 (19%) had recurrence of DTC over median follow-up of 6.6 years (IQR 5.3–9.3). The sensitivity and specificity of US in diagnosing cervical recurrence were 73.3% (95% CI 0.51–0.96) and 68.3% (95% CI 0.60–0.77) based on historical reports, respectively, and 80% (95% CI 0.60-1.00) and 87.8% (95% CI 0.82–0.93) based on blinded expert review, respectively. Tg had a sensitivity of 95.5% (95% CI 0.89-1.0) and specificity of 96.2% (95% CI 0.92–0.99) in detecting cervical recurrence or distant metastases. False positive US findings on historical US and subsequent review occurred in 38 (28%) and 15 (11%) patients, respectively, while 5 (3.6%) had false positive Tg results.ConclusionSerial Tg has better sensitivity and specificity than US for detecting recurrence of advanced stage DTC. Furthermore, re-interpretation of abnormal findings using structured US reporting with a subspecialized reader may improve diagnostic performance of US and improve its utility in clinical care.

Exploring the Integration of Chinese Music in Western Musicological Literature: Trends, Gaps, and Multicultural Perspectives

The purpose of the article is to analyse Western musicological literature to identify key trends and gaps in existing research on Chinese music as an integral part of the contemporary multicultural educational space. The research methodology is based on content analysis, comparative analysis, and bibliographic review. The primary method is content analysis, involving a systematic review of academic articles, monographs, reviews, and other publications on Chinese music in Western musicological literature. Comparative analysis is used to compare Western research on Chinese music with scholarly work from China and other countries. Bibliographic review helps to identify scientific gaps and trends in Chinese music research. The scientific novelty of the study lies in the comprehensive analysis of Western musicological literature on Chinese music to reveal key trends and gaps in existing research. The use of content analysis, comparative analysis, and bibliographic review allows for the first systematic organisation and comparison of approaches to studying Chinese music in different cultural contexts. The study also provides new insights into the role of Chinese music in the contemporary multicultural educational space, contributing to its integration and popularisation. Conclusions. Over the past three decades, publications on Chinese music within the context of multicultural music education have been irregular. Although the number of studies is not large, it shows moderate activity in the 1990s and early 2000s, with a noticeable increase after 2007 and periods of decline between 2010 and 2014. This indicates the need for further analysis of the reasons behind this dynamic and a deeper exploration of the integration of Chinese music into the Western educational context. The literature review shows that research covers a broad range of educational contexts, from early childhood to higher education and teacher professional development, indicating the potential for integrating Chinese music at various levels of formal education. The review also reveals that research on Chinese music often has a Eurocentric approach, evaluating it through the lens of Western music theory. This limits the full understanding and integration of Chinese musical traditions, highlighting the need for a deeper and more comprehensive approach that would foster an understanding of Chinese music in its own context.

Durvalumab after Chemoradiotherapy in Limited-Stage Small-Cell Lung Cancer.

Adjuvant therapy with durvalumab, with or without tremelimumab, may have efficacy in patients with limited-stage small-cell lung cancer who do not have disease progression after standard concurrent platinum-based chemoradiotherapy. In a phase 3, double-blind, randomized, placebo-controlled trial, we assigned patients to receive durvalumab at a dose of 1500 mg, durvalumab (1500 mg) plus tremelimumab at a dose of 75 mg (four doses only), or placebo every 4 weeks for up to 24 months. Randomization was stratified according to disease stage (I or II vs. III) and receipt of prophylactic cranial irradiation (yes vs. no). Results of the first planned interim analysis of the two primary end points of overall survival and progression-free survival (assessed on the basis of blinded independent central review according to the Response Evaluation Criteria in Solid Tumors, version 1.1) with durvalumab as compared with placebo (data cutoff date, January 15, 2024) are reported; results in the durvalumab-tremelimumab group remain blinded. A total of 264 patients were assigned to the durvalumab group, 200 to the durvalumab-tremelimumab group, and 266 to the placebo group. Durvalumab therapy led to significantly longer overall survival than placebo (median, 55.9 months [95% confidence interval {CI}, 37.3 to not reached] vs. 33.4 months [95% CI, 25.5 to 39.9]; hazard ratio for death, 0.73; 98.321% CI, 0.54 to 0.98; P = 0.01), as well as to significantly longer progression-free survival (median 16.6 months [95% CI, 10.2 to 28.2] vs. 9.2 months [95% CI, 7.4 to 12.9]; hazard ratio for progression or death, 0.76; 97.195% CI, 0.59 to 0.98; P = 0.02). The incidence of adverse events with a maximum grade of 3 or 4 was 24.4% among patients receiving durvalumab and 24.2% among patients receiving placebo; adverse events led to discontinuation in 16.4% and 10.6% of the patients, respectively, and led to death in 2.7% and 1.9%. Pneumonitis or radiation pneumonitis with a maximum grade of 3 or 4 occurred in 3.1% of the patients in the durvalumab group and in 2.6% of those in the placebo group. Adjuvant therapy with durvalumab led to significantly longer overall survival and progression-free survival than placebo among patients with limited-stage small-cell lung cancer. (Funded by AstraZeneca; ADRIATIC ClinicalTrials.gov number, NCT03703297.).

High on sparsity: Interbin compensation of cardiac motion for improved assessment of left-ventricular function using 5D whole-heart MRI.

Cardiac magnetic resonance is the gold standard for evaluating left-ventricular ejection fraction (LVEF). Standard protocols, however, can be inefficient, facing challenges due to significant operator and patient involvement. Although the free-running framework (FRF) addresses these challenges, the potential of the extensive data it collects remains underutilized. Therefore, we propose to leverage the large amount of data collected by incorporating interbin cardiac motion compensation into FRF (FRF-MC) to improve both image quality and LVEF measurement accuracy, while reducing the sensitivity to user-defined regularization parameters. FRF-MC consists of several steps: data acquisition, self-gating signal extraction, deformation field estimations, and motion-resolved reconstruction with interbin cardiac motion compensation. FRF-MC was compared with the original 5D-FRF method using LVEF and several image-quality metrics. The cardiac regularization weight ( ) was optimized for both methods by maximizing image quality without compromising LVEF measurement accuracy. Evaluations were performed in numerical simulations and in 9 healthy participants. In vivo images were assessed by blinded expert reviewers and compared with reference standard 2D-cine images. Both in silico and in vivo results revealed that FRF-MC outperformed FRF in terms of image quality and LVEF accuracy. FRF-MC reduced temporal blurring, preserving detailed anatomy even at higher cardiac regularization weights, and led to more accurate LVEF measurements. Optimized produced accurate LVEF for both methods compared with the 2D-cine reference (FRF-MC: 0.59% [-7.2%, 6.0%], p = 0.47; FRF: 0.86% [-8.5%, 6.7%], p = 0.36), but FRF-MC resulted in superior image quality (FRF-MC: 2.89 ± 0.58, FRF: 2.11 ± 0.47; p < 10-3). Incorporating interbin cardiac motion compensation significantly improved image quality, supported higher cardiac regularization weights without compromising LVEF measurement accuracy, and reduced sensitivity to user-defined regularization parameters.

Pembrolizumab for the First-Line Treatment of Recurrent Locally Advanced or Metastatic Merkel Cell Carcinoma: Results from the Single-Arm, Open-Label, Phase III KEYNOTE-913 Study.

The phase III KEYNOTE-913 study was conducted to evaluate the efficacy and safety of pembrolizumab as first-line therapy in patients with advanced Merkel cell carcinoma (MCC). The aim was to report results from the primary analysis of KEYNOTE-913. Patients with recurrent locally advanced or metastatic MCC received pembrolizumab 200mg intravenously every 3weeks for up to 35 treatments (~2 years). The primary end point was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) by blinded independent central review (BICR). Secondary end points were duration of response (DOR) and progression-free survival (PFS) per RECIST v1.1 by BICR, overall survival (OS), and safety and tolerability. Fifty-five patients were treated with pembrolizumab. The median time from first dose to data cutoff (February 15, 2024) was 50.3 months (range 38.7-59.4). The ORR was 49% (95% confidence interval [CI] 35-63), with 12 complete responses and 15 partial responses. The median DOR was 39.8 months (range 4.8-52.5+), and the 24-month DOR rate was 69%. The median PFS was 9.3 months (95% CI 3-26), and the 24-month PFS rate was 39%. The median OS was 24.3 months (95% CI 12.4 to not reached), and the 24-month OS rate was 51%. Any-grade treatment-related adverse events (AEs) occurred in 38 patients (69%); 13 patients (24%) experienced grade 3-5 AEs. The most common treatment-related AEs were fatigue (n = 12 [22%]), pruritus (n = 12 [22%]), and lipase increase (n = 10 [18%]). One patient died of treatment-related Guillain-Barré syndrome. Pembrolizumab provided durable antitumor activity and promising survival and had a manageable safety profile in patients with recurrent locally advanced or metastatic MCC, supporting its use in this population. Clinicaltrials.gov, NCT03783078.

GOG-3097/ENGOT-ov81/GTG-UK/RAMP 301: a phase 3, randomized trial evaluating avutometinib plus defactinib compared with investigator’s choice of treatment in patients with recurrent low grade serous ovarian cancer

BackgroundThere are no approved treatments specifically for low grade serous ovarian cancer; current standard of care treatment options are limited in efficacy and tolerability. The combination of avutometinib with defactinib...

Clinical applications of STING agonists in cancer immunotherapy: current progress and future prospects.

The STING (Stimulator of Interferon Genes) pathway is pivotal in activating innate immunity, making it a promising target for cancer immunotherapy. STING agonists have shown potential in enhancing immune responses, particularly in tumors resistant to traditional therapies. This scholarly review examines the diverse categories of STING agonists, encompassing CDN analogues, non-CDN chemotypes, CDN-infused exosomes, engineered bacterial vectors, and hybrid structures of small molecules-nucleic acids. We highlight their mechanisms, clinical trial progress, and therapeutic outcomes. While these agents offer significant promise, challenges such as toxicity, tumor heterogeneity, and delivery methods remain obstacles to their broader clinical use. Ongoing research and innovation are essential to overcoming these hurdles. STING agonists could play a transformative role in cancer treatment, particularly for patients with hard-to-treat malignancies, by harnessing the body's immune system to target and eliminate cancer cells.

Bempegaldesleukin plus nivolumab in first-line advanced/metastatic urothelial carcinoma: Results from a phase II single-arm study (PIVOT-10)

BackgroundIn PIVOT-02, bempegaldesleukin (BEMPEG), a pegylated interleukin-2 cytokine prodrug, in combination with nivolumab (NIVO), a Programmed cell death protein 1 inhibitor, demonstrated the potential to provide additional benefits over immune checkpoint inhibitor monotherapy in patients with urothelial carcinoma, warranting further investigation. We evaluated BEMPEG plus NIVO in cisplatin-ineligible patients with previously untreated locally advanced or metastatic urothelial carcinoma. MethodsThis open-label, multicenter, single-arm, phase II study enrolled patients with locally advanced/surgically unresectable or metastatic urothelial carcinoma and who were ineligible for cisplatin-based treatment. Patients received BEMPEG plus NIVO were administered intravenously every 3 weeks for ≤2 years or until progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by blinded independent central review (BICR) in patients with low programmed death ligand-1 (PD-L1) expression. Secondary endpoints included ORR and duration of response in the overall population. Progression-free survival (PFS) and overall survival (OS) were exploratory endpoints. ResultsOne hundred and eighty-eight patients were enrolled; 123 patients were PD-L1 low (combined positive score [CPS] <10; 65.4%), 59 were PD-L1 high (31.4%; CPS ≥10), and 6 had PD-L1 status unknown (3.2%). ORR per blinded independent central review in patients with PD-L1-low tumors was 17.9% (95% confidence interval [CI] 11.6–25.8) while in all treated patients was 19.7% (95% CI 14.3–26.1). Median PFS and OS in the overall population were 3.0 months and 12.6 months, respectively. BEMPEG plus NIVO combination was well tolerated, with a safety profile similar to previously reported trials; no new or unexpected safety signals were reported. ConclusionsBEMPEG plus NIVO did not meet the efficacy threshold for ORR in patients with previously untreated locally advanced or metastatic urothelial carcinoma and low PD-L1 expression.

OSAIRIS: Lessons Learned from the Hospital-Based Implementation and Evaluation of an Open-Source Deep-Learning Model for Radiotherapy Image Segmentation

Several studies report the benefits and accuracy of using autosegmentation for organ at risk (OAR) outlining in radiotherapy treatment planning. Typically, evaluations focus on accuracy metrics, and other parameters such as perceived utility and safety are routinely ignored. Here we report our finding from the implementation and clinical evaluation of OSAIRIS, an open-source AI model for radiotherapy image segmentation, that was carried out as part of its development into a medical device. The device contours OARs in the head and neck and male pelvis (referred to as the prostate model), and is designed to be used as a time-saving workflow device, alongside a clinician. Unlike standard evaluation processes, which heavily rely on accuracy metrics alone, our evaluation sought to demonstrate the tangible benefits, quantify utility and assess risk within a specific clinical workflow. We evaluated the time-saving benefit this device affords to clinicians, and how this time-saving might be linked to accuracy metrics, as well as the clinicians’ assessment of the usability of the OSAIRIS contours in comparison to their colleagues’ contours and those from other commercial AI contouring devices. Our safety evaluation focused on whether clinicians can notice and correct any errors should they be included in the output of the device.We found that OSAIRIS affords a significant time-saving of 36% (5.4 ± 2.1 minutes) when used for prostate contouring and 67% (30.3 ± 8.7 minutes) for head and neck contouring. Combining editing time data with accuracy metrics, we found the Hausdorff distance best correlated with editing-time, outperforming dice, the industry-standard, with a Spearman correlation coefficient of 0.70, and a Kendall coefficient of 0.52. Our safety and risk-mitigation exercise showed that anchoring bias is present when clinicians edit AI-generated contours, with the effect seemingly more pronounced for some structures over others. Most errors, however, were corrected by clinicians, with 72% of the head and neck errors 81% of the prostate errors removed in the editing step. Notably, our blinded clinician contour rating exercise showed that gold standard clinician contours are not rated more highly than the AI-generated contours.We conclude that evaluations of AI in a clinical setting must consider the clinical workflow in which the device will be used, and not rely on accuracy metrics alone, in order to reliably assess the benefits, utility and safety of the device. The effects of human-AI inter-operation must be evaluated to accurately assess the practical usability and potential uptake of the technology, as demonstrated in our blinded clinical utility review. The clinical risks posed by the use of the device must be studied and mitigated as far as possible, and our ‘Mystery Shopping’ experiment provides a template for future such assessments.

Validation of a 3D-Printed Silicone-Based Laryngeal Model for Resident Education.

We sought to validate a laryngeal simulation model and subsequently demonstrate its efficacy in improving surgical technique. Pre-post interventional study. Otolaryngology Program at a Tertiary Care Center. A low-cost, high-fidelity laryngeal model was created using a 3-dimensional-printed cast and multilayered silicone to mimic vocal fold lesions. Participants (attendings and trainees) were first given a series of tasks including mucosal vocal fold lesion resection and microflap excision of a submucosal lesion. Trainees were then provided with an instructional video from a laryngologist and asked to repeat the same tasks on the model. Performance data was then assessed using validated surveys and blinded expert reviewers. Eighteen participants completed the simulation. All subjects agreed that the "simulation experience was useful" and 93% agreed "the simulator helped improve my ability to do microsurgical tasks." In the postinstruction self-evaluation, trainees reported a significant decrease in mental demand (95% confidence interval [CI]: 0.37-0.91; P = .038) and significant increase in subjective performance (95% CI: 1.51-51.89; P = .016) compared to the preinstruction self-evaluation. On the postinstruction attempt, there was a significant improvement in all domains of the adapted objective structured assessment of technical skills as measured by 3 blinded, expert reviewers. This study demonstrates the usefulness of a silicone larynx model and the value of instructional video in developing laryngeal microsurgical skills. Participants positively reviewed the laryngeal model and trainees saw both a subjective and objective improvement indicating tangible operative benefits from the use of this laryngeal simulation.

Valemetostat for patients with relapsed or refractory peripheral T-cell lymphoma (VALENTINE-PTCL01): a multicentre, open-label, single-arm, phase 2 study.

Peripheral T-cell lymphomas are aggressive non-Hodgkin lymphomas with few treatment options for relapsed or refractory disease. Valemetostat tosylate (valemetostat) is a potent, novel, dual inhibitor of EZH2 and EZH1. We investigated the clinical activity and safety of valemetostat in patients with relapsed or refractory peripheral T-cell lymphoma, and its safety in patients with relapsed or refractory adult T-cell leukaemia/lymphoma. VALENTINE-PTCL01 was a multicentre, open-label, single-arm, phase 2 trial performed at 47 hospitals in 12 countries across Asia, Europe, North America, and Oceania. Patients with either peripheral T-cell lymphoma or adult T-cell leukaemia/lymphoma, aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-2 received oral valemetostat at 200 mg per day in continuous 28-day cycles until disease progression or unacceptable toxicity. The primary endpoint for patients with peripheral T-cell lymphoma was the CT-based objective response rate by blinded independent central review (BICR) using 2014 Lugano response criteria. Patients who received valemetostat and had a confirmed eligible peripheral T-cell lymphoma subtype on central review were included in the efficacy analysis. The primary endpoint for patients with adult T-cell leukaemia/lymphoma was the safety and tolerability of valemetostat. Safety in both cohorts was assessed in all patients who received at least one dose of valemetostat. The trial is registered with ClinicalTrials.gov, NCT04703192, and EudraCT, 2020-004954-31, and is closed to enrolment. Between June 16, 2021, and Aug 10, 2022, 133 patients with relapsed or refractory peripheral T-cell lymphoma (median age 69·0 years [IQR 58·0-74·0]; 91 [68%] were male, and 42 [32%] were female) and 22 patients with adult T-cell leukaemia/lymphoma (66·5 years [54·0-73·0]; 15 [68%] were male, and seven [32%] were female) were enrolled. The median follow-up time was 12·3 months (95% CI 11·8-13·8). 52 (44%; 95% CI 35-53) of 119 efficacy-evaluable patients with relapsed or refractory peripheral T-cell lymphoma had an objective response. The most common grade 3-4 adverse events were thrombocytopenia (31 [23%] of 133 patients in the peripheral T-cell lymphoma group and 11 [50%] of 22 patients in the adult T-cell leukaemia/lymphoma group), anaemia (25 [19%] and ten [46%]), and neutropenia (23 [17%] and four [18%]). Serious treatment-emergent adverse events were reported in 53 (40%) patients with peripheral T-cell lymphoma and 15 (68%) patients with adult T-cell leukaemia/lymphoma; nine (7%) patients and one (5%) patient had a serious treatment-emergent adverse event considered to be treatment related, respectively. No treatment-related deaths were reported. These data show that treatment with valemetostat leads to durable responses in patients with relapsed or refractory peripheral T-cell lymphoma, with a manageable safety profile. Daiichi Sankyo.

Cadonilimab plus platinum-based chemotherapy with or without bevacizumab as first-line treatment for persistent, recurrent, or metastatic cervical cancer (COMPASSION-16): a randomised, double-blind, placebo-controlled phase 3 trial in China

Cadonilimab is a bispecific antibody targeting PD-1 and CTLA-4, which has shown substantial clinical benefits in advanced cervical cancer. In the COMPASSION-16 trial, we aimed to evaluate the addition of cadonilimab to first-line standard chemotherapy in persistent, recurrent, or metastatic cervical cancer. In this randomised, double-blind, multicentre, placebo-controlled phase 3 trial, women aged 18-75 years across 59 clinical sites in China with previously untreated persistent, recurrent, or metastatic cervical cancer were randomly assigned (1:1) to receive cadonilimab (10 mg/kg) or placebo plus platinum-based chemotherapy with or without bevacizumab every 3 weeks for six cycles, followed by maintenance therapy every 3 weeks for up to 2 years. Randomisation was performed centrally through an interactive web-response system. Stratification factors were the use of bevacizumab (yes or no) and previous concurrent chemoradiotherapy (yes or no). The dual primary outcomes were progression-free survival as assessed by blinded independent central review and overall survival in the full analysis set. This study is registered with ClinicalTrials.gov, NCT04982237; the study has completed enrolment and is ongoing for treatment and follow-up. 445 eligible women were enrolled between Sept 11, 2021, and June 23, 2022. Median progression-free survival was 12·7 months (95% CI 11·6-16·1) in the cadonilimab group and 8·1 months (7·7-9·6) in the placebo group (hazard ratio 0·62 [95% CI 0·49-0·80], p<0·0001); median overall survival was not reached (27·0 months to not estimable) versus 22·8 months (17·6-29·0), respectively (hazard ratio 0·64 [0·48-0·86], p=0·0011). The most common grade 3 or higher adverse events were decreased neutrophil count, decreased white blood cell count, and anaemia. The addition of cadonilimab to first-line standard chemotherapy significantly improved progression-free survival and overall survival with a manageable safety profile in participants with persistent, recurrent, or metastatic cervical cancer. The data support the use of cadonilimab plus chemotherapy as an efficacious first-line therapy in persistent, recurrent, or metastatic cervical cancer. Akeso Biopharma.