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Wenzhen Ge,1 Ning Wu,1 Chieh-I Chen,1 Timothy J Inocencio,1 Patrick R LaFontaine,2 Frank Seebach,3 Matthew Fury,4 James Harnett,1 Emily S Ruiz5 1Department of Health Economics and Outcomes Research, Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA; 2Department of Global Health Economics & Outcomes Research, Sanofi, Cambridge, MA, USA; 3Department of Regulatory Affairs, Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA; 4Department of Clinical Sciences, Oncology, Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA; 5Department of Dermatology, Dana-Farber Cancer Institute, Boston, MA, USACorrespondence: Wenzhen Ge, Regeneron Pharmaceuticals, Inc, 1 Rockwood Road, Sleepy Hollow, NY, 10591, Tel +1 914-847-7000, Email wenzhen.ge@regeneron.comBackground: Prior to the Food and Drug Administration approval of cemiplimab in 2018, the median overall survival (OS) for adult patients with advanced CSCC receiving systemic therapy was approximately 8 to 15 months. Limited real-world data are available on cemiplimab for this indication in the US.Patients and Methods: This retrospective cohort study included US patients with advanced CSCC initiating cemiplimab monotherapy in a real-world database (2018– 2021). A clinical trial–like sub-cohort was identified using select criteria. Time to treatment discontinuation (TTD), time to next treatment (TTNT), and OS were estimated using Kaplan–Meier methods. Cox proportional hazard models were used to examine prognostic factors associated with OS in the main cohort.Results: The main cohort included 622 patients (n = 240 in the trial-like cohort). In the main cohort, the median age was 78 years, 77.8% were male, 21.4% were immunocompromised/immunosuppressed, and 63.8% had metastatic CSCC. Median (95% CI) TTD and TTNT were 8.0 (6.6– 9.0) months and 16.4 (13.3– 21.0) months, respectively, in the main cohort. Median (95% CI) OS was 24.8 (21.8– 29.1) months in the main cohort (not reached in the trial-like cohort). In multivariable analyses, age < 60 years (hazard ratio [HR], 0.37), Eastern Cooperative Oncology Group performance status < 3– 4 (HR range, 0.13– 0.57), and primary CSCC location in the head and neck only versus extremities only (HR, 0.59) were associated with better OS. Similar OS was observed between patients who had immunosuppressing/immunocompromising conditions and those without.Conclusion: These findings confirm the effectiveness of cemiplimab among a heterogenous, real-world advanced CSCC patient population and substantiate the efficacy of cemiplimab observed in clinical trials.Keywords: cutaneous squamous cell carcinoma, cemiplimab, immune checkpoint inhibitor, real-world study, skin cancer

Objective: To investigate the efficacy and safety of an oral complementary medicine combination formulation relative to placebo, on changes in pain intensity from baseline to week 12, in people with knee osteoarthritis (OA)., Design: A placebo-controlled, double-blind, two-arm, superiority, phase II, Randomized Controlled Trial (RCT) (ACTRN12623000380695). We will recruit 82 participants (∼41 per arm), aged ≥40 years, with a clinical diagnosis of symptomatic knee OA and radiographic change on x-ray (Kellgren-Lawrence Grade ≥2). Participants will be randomly allocated to receive either a complementary medicine formulation containing a daily dose of Boswellia serrata extract (Boswellin® Super, 250 ​mg/day), pine bark extract (Fenoprolic™ 70 Organic 100 ​mg/day), curcumin (500 ​mg/day), piperine (5 ​mg/day), and methylsulfonylmethane (MSM, 1500 ​mg/day), or placebo, for 12-weeks. The primary endpoint will be change from baseline in average knee pain intensity at 12-weeks (visual analogue scale). Secondary endpoints will include change in knee pain from baseline to 12-weeks in the Knee Injury and Osteoarthritis Outcome Score (KOOS), global assessment of disease activity, global rating of change, and health-related quality of life (AQoL-8D)., Ethics and Dissemination: This protocol has been approved by the University of Sydney Human Research Ethics Committee (#2021/877). Dissemination will occur through lay summaries, infographics, conference abstracts, oral presentations, theses, and scientific publications., Conclusion: This RCT will provide credible evidence about the efficacy and safety of this complementary medicine combination and inform updates to international clinical practice standards on the use of complementary medicines in the management of symptomatic knee OA., Competing Interests: JLB is supported by an unrestricted Fellowship grant from Haleon Australia and is employed by the University of Sydney. DJH is the editor of the osteoarthritis section for UpToDate and co-editor in Chief of Osteoarthritis and Cartilage. DJH provides consulting advice on scientific advisory boards for Haleon, Pfizer, Lilly, TLCBio, Novartis, Tissuegene, and Biobone. JHar has received payments, travel and/or accommodation for providing expert advice about traditional, complementary and integrative medicine to industry, government bodies and non-government organizations. They have spoken at conferences and/or provided consultations for which honoraria, registration, travel and/or accommodation have been paid for by the organizers. LD and SR receive royalties from UpToDate. AJM has provided educational services for Bayer and served on a clinical advisory board for Viatris. The Sydney Pharmacy School receives research funding for a postgraduate scholarship from GlaxoSmithKline for a PhD scholar under the supervision of AJM., (© 2024 The Author(s).)

Background: There is limited knowledge of how US managed care professionals view and prioritize quality metrics/performance measures, care models, alternative payment models, and clinical pathways in oncology settings., Objective: To characterize payor perspectives on, and the use of, oncology clinical pathways and performance measures in their reimbursement/access decision-making process., Methods: A survey was implemented via SurveyMonkey software and distributed electronically to a national sample of the Academy of Managed Care Pharmacy (AMCP) Market Insights Panel members from July 11 through August 5, 2022. The survey was created by a steering committee based on literature reviews of the current and future oncology care landscapes. The survey consisted of 47 questions, including those to establish respondents' position, responsibilities, and demographics. The results are presented as descriptive statistics for 7 key questions that covered the perceptions and use of quality metrics/performance measures, alternative payment models, and oncology care pathways as prioritized by the steering committee., Results: Among the 695 AMCP panel members who were sent the survey, 73 responded (response rate 10.5%), 54 were eligible to continue, and 31 completed the entire questionnaire; the low response rate may limit generalizability of the survey results. Specific oncology clinical and economic measures of performance were currently used (70%-88%) but generally received less endorsement for future use (39%-49%) except for chemotherapy during end of life, which was considered for future use by 80% of respondents but was only currently used by 31%. Benchmarking was the primary reason for the use of performance measures; only 27% used these to inform value-based agreements. Real-world data tracked by respondents' institutions primarily focused on managed care and pharmacy utilization (39%-85%), with patient-reported and clinical outcomes tracked by only 17%-34%. Almost one-third (31%) did not use clinical oncology pathways, and among those who did, fewer than half (48%) reported that their organization tracks whether treatment decisions agree with the oncology care pathways, and only 26% reported feedback to oncology providers on how often their treatment decisions agree with the pathways. When considering alternative payment models, patient-related components received lower rankings in importance than clinical relevance, actionability, and costs., Conclusions: Variation among payors regarding current trends in oncology care management, including on the importance of patient-centric outcomes and the use of oncology clinical pathways, suggests the need to focus on value-based health care and greater uptake of oncology clinical pathways.

In this paper we investigate the effects of varying cation valency and concentration on the rheology of entangled λ DNA solutions. We show that monovalent cations moderately increase the viscoelasticty of the solutions mainly by stabilising linear concatenation of λ DNA "monomers" via hybridisation of their sticky ends. On the contrary, divalent cations have a far more complex and dramatic effect on the rheology of the solution and we observe evidence of inter-molecular DNA-DNA bridging by Mg 2+ . We argue that these results may be interesting in the context of dense solutions of single and double stranded DNA, e.g. in vivo or in biotechnology applications such as DNA origami and DNA hydrogels.

Background: Australian government strategies and frameworks have been developed in recent years to encourage the integration and coordination of primary care delivery; including patient-centred approaches to clinical and preventative care, and health promotion. This study aims to explore patient experiences of information-sharing and patient-centred care across various primary care clinical settings, with a particular focus on clinical encounters with GPs, naturopaths, osteopaths and acupuncturists., Methods: Data about healthcare utilisation and experiences from a 63-item cross-sectional survey obtained from a nationally representative sample of Australian adults aged ≥ 18 years were analysed. Chi-square and Kruskal-Wallis H tests were used to explore differences in the experiences of knowledge and information sharing during GP consultations among those who also consulted with a naturopath, osteopath or acupuncturist, compared those who had not. Logistic regression was used to investigate correlations between participants perceptions about GP consultation outcomes, and the GP's information-sharing behaviour or perceived experience of patient-centredness., Results: Across 2354 participants, verbal explanation (76.3%) and/or individualised handouts (16.8%) were the most common type of information shared in GP consultations. Individuals who consulted with a GP and a naturopath, an osteopath, or an acupuncturist reported a lower rate of receiving a verbal explanation from their GP but higher rate of receiving other types of information sources including handouts. Over one quarter of study participants who visited a GP did not discuss any of their health information with their GP. Information sharing was lower for individuals who also visited a naturopath, osteopath or acupuncturist. Participants scored their consultations with a GP as patient-centred, but these scores were lower among participants who also consulted with at least one other primary care practitioner type included in the study., Conclusions: Public health and health services researchers, policymakers and leaders of primary care professions have a role and responsibility to ensure practitioners are confident and competent in sharing health information with their patients that considers their health literacy needs, and the importance of patient-centred care. Research focussed on a more in-depth understanding of the differences and relationships observed across the primary care landscape in this study is recommended., (© 2024. The Author(s).)

Aim: To evaluate health-related quality of life (HRQoL) in cemiplimab-treated patients with locally advanced basal cell carcinoma (laBCC). Materials & methods: Eighty-four patients with laBCC received cemiplimab 350 mg every 3 weeks (up to 9 cycles). HRQoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Core 30 (QLQ-C30) and Skindex-16 questionnaires at baseline and each cycle. Mixed-effects repeated-measures models evaluated change from baseline across cycles. Results: Clinically meaningful improvement or maintenance was reported by 62-90% of patients on QLQ-C30 scales and by approximately 80% on Skindex-16 scales at Cycle 2, with consistent results at Cycle 9 except fatigue. Conclusion: Most cemiplimab-treated patients with laBCC reported improvement or maintenance of HRQoL with low symptom burden except fatigue. Clinical Trial Registration: ClinicalTrials.gov identifier NCT03132636, registered 28 April 2017.