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Aikaterini Bilitou,1 John Were,2 Archie Farrer,2 Adrian Rabe,2,3 Simon Wan Yau Ming,2 Inaam Haq,1 Kyle Dunton4 1Daiichi Sankyo Europe GmbH, Munich, Bayern, Germany; 2Health iQ Ltd, London, UK; 3Imperial College London, London, UK; 4Daiichi Sankyo UK Ltd, Uxbridge Business Park, Uxbridge, UKCorrespondence: Aikaterini Bilitou, Health Economics and Outcomes Research, Daiichi Sankyo Europe GmbH, Zielstattstrasse 48, Munich, 81379, Bayern, Germany, Tel +49 897 808802, Email aikaterini.bilitou@daiichi-sankyo.euBackground: Guidelines for the management of dyslipidemias recommend intensive low-density lipoprotein (LDL-C) control through lifestyle advice and lipid-lowering drugs to reduce the risk of cardiovascular disease (CVD).Objective: This retrospective study aimed to characterize the adult primary care population with primary hypercholesterolemia (PH)/mixed dyslipidemia (MD).Methods: Data on adults with PH/MD between 1 January 2009 and 31 December 2019 in the UK were extracted from linked primary Clinical Practice Research Datalink (CPRD) and secondary care (Hospital Episode Statistics) datasets and analyzed.Results: A total of 279,221 patients met the inclusion criteria. Mean follow-up was 8.6 years. Crude prevalence of PH/MD increased from 13.5% in 2009 to 23.5% by 2019. The incidence decreased from 176 to 49 per 100,000 population. Mean age of the cohort was 58 years, baseline LDL-C was 4.32 mmol/L, 19.6% had atherosclerotic CVD, 30.1% diabetes, and 8.5% heterozygous familial hypercholesterolemia. Estimated LDL-C reductions of 40% and 50% were achieved in 2.6% and 2.3% of patients, respectively. Most received moderate-intensity statins as monotherapy (62.4%); high-intensity statins were used less frequently (24.3% as initial treatment). Less than 10% of patients received ezetimibe plus statins of different intensities.Conclusion: The prevalence of dyslipidemia doubled between 2009 and 2019, likely due to more systematic identification of PH/MD. A large proportion of patients with PH/MD are of high and very high CV risk, remain suboptimally treated in terms of lipid lowering, and may experience CV events with associated non-negligible clinical and economic sequelae. Despite intensive LDL-C-lowering recommendations, these do not translate in clinical practice to the wider population.Keywords: lipid management, atherosclerosis, cardiovascular disease, NICE guidelines

Environmental changes associated with rapid climate change in the Arctic, such as the increased rates of sedimentation from climatic or anthropogenic sources, can enhance the impact of abiotic stressors on coastal ecosystems. High sedimentation rates can be detrimental to nearshore kelp abundance and distribution, possibly due to increased mortality at the spore settlement stage. Spore settlement and viability of the Arctic kelp Laminaria solidungula were examined through a series of lab-based sedimentation experiments. Spores were exposed to increasing sediment loads in three experimental designs simulating different sedimentation scenarios: sediment deposition above settled spores, settlement of spores on sediment-covered substrate, and simultaneous suspension of spores and sediments during settlement. Spore settlement was recorded upon completion of each experiment, and gametophyte abundance was assessed following a growth period with sediments removed to examine short-term spore viability via a gametophyte-to-settled-spore ratio. In all three types of sediment exposure, the addition of sediments caused a 30%-40% reduction in spore settlement relative to a no-sediment control. Spore settlement decreased significantly between the low and high sediment treatments when spores were settled onto sediment-covered substrates. In all experiments, increasing amounts of sediment had no significant effect on spore viability, indicating that spores that had settled under different short-term sediment conditions were viable. Our results indicate that depending on spore-sediment interaction type, higher rates of sedimentation resulting from increased sediment loading could affect L. solidungula spore settlement success with potential impacts on the long-term persistence of a diverse and productive benthic habitat., (© 2024 Phycological Society of America.)

Background: In DESTINY-Breast02, patients with HER2-positive unresectable or metastatic breast cancer who received trastuzumab deruxtecan demonstrated superior progression-free and overall survival compared with those receiving treatment of physician's choice. We present the patient-reported outcomes (PROs) and hospitalisation data., Methods: In this randomised, open-label, phase 3 trial conducted at 227 clinical sites globally, enrolled patients had to be aged 18 years or older with HER2-positive unresectable or metastatic breast cancer that had progressed on trastuzumab emtansine and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (2:1) using block randomisation (block size of 3) to receive trastuzumab deruxtecan (5·4 mg/kg intravenously once every 21 days) or treatment of physician's choice by an independent biostatistician using an interactive web-based system. Patients and investigators remained unmasked to treatment. Treatment of physician's choice was either capecitabine (1250 mg/m 2 orally twice per day on days 1-14) plus trastuzumab (8 mg/kg intravenously on day 1 then 6 mg/kg once per day) or capecitabine (1000 mg/m 2 ) plus lapatinib (1250 mg orally once per day on days 1-21), with a 21-day schedule. The primary endpoint, which was progression-free survival based on blinded independent central review, has previously been reported. PROs were assessed in the full analysis set (all patients randomly assigned to the study) using the oncology-specific European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), breast cancer-specific EORTC Quality of Life Questionnaire Breast 45 (QLQ-BR45), and the generic HRQoL EQ-5D-5L questionnaire. Analyses included change from baseline and time to definitive deterioration for PRO variables of interest and hospitalisation-related endpoints. This study is registered with ClinicalTrials.gov, NCT03523585, and is closed to recruitment., Findings: Between Sept 6, 2018, and Dec 31, 2020, 608 patients were randomly assigned to receive either trastuzumab deruxtecan (n=406; two did not receive treatment) or treatment of physician's choice (n=202; seven did not receive treatment). Overall, 603 patients (99%) were female and five (<1%) were male. The median follow-up was 21·5 months (IQR 15·2-28·4) in the trastuzumab deruxtecan group and 18·6 months (IQR 8·8-26·0) in the treatment of physician's choice group. Median treatment duration was 11·3 months (IQR 6·2-20·5) in the trastuzumab deruxtecan group and approximately 4·5 months in the treatment of physician's choice group (4·4 months [IQR 2·5-8·7] with trastuzumab; 4·6 months [2·1-8·9] with capecitabine; and 4·5 months [2·1-10·6] with lapatinib). Baseline EORTC QLQ-C30 global health status (GHS) scores were similar with trastuzumab deruxtecan (n=393) and treatment of physician's choice (n=187), and remained stable with no clinically meaningful change (defined as ≥10-point change from baseline) over time. Median time to definitive deterioration was delayed with trastuzumab deruxtecan compared with treatment of physician's choice for the primary PRO variable EORTC QLQ-C30 GHS (14·1 months [95% CI 10·4-18·7] vs 5·9 months [4·3-7·9]; HR 0·5573 [0·4376-0·7099], p<0·0001) and all other prespecified PROs (EORTC QLQ-C30 subscales, EORTC QLQ-BR45 arm and breast symptoms, and EQ-5D-5L visual analogue scale). Patient hospitalisation rates were similar in the trastuzumab deruxtecan (92 [23%] of 406) and treatment of physician's choice (41 [20%] of 202) groups; however, median time to hospitalisation was 133 days (IQR 56-237) with trastuzumab deruxtecan versus 83 days (30-152) with treatment of physician's choice., Interpretation: Overall, GHS and quality of life were maintained for both treatment groups, with prespecified PRO variables favouring trastuzumab deruxtecan over treatment of physician's choice, suggesting that despite a longer treatment duration, there was no detrimental impact on patient health-related quality of life with trastuzumab deruxtecan. When considered with efficacy and safety data from DESTINY-Breast02, these results support the overall benefit of trastuzumab deruxtecan for patients with HER2-positive unresectable or metastatic breast cancer previously treated with trastuzumab emtansine., Funding: Daiichi Sankyo and AstraZeneca., Competing Interests: Declaration of interests TF reports payments to their institution from Roche, Novartis, Pfizer, Daiichi Sankyo, MSD, and Eisai. FC, KD, and WL are full-time employees at Daiichi Sankyo. FA reports institutional research grants from Novartis, Pfizer, AstraZeneca, Eli Lilly, Daiichi Sankyo, and Roche, as well as consulting fees paid to their institution by MedImmune, Gilead, Relay Therapeutics, and Guardant Health. IK reports support for the present manuscript received by their institution from AstraZeneca and Daiichi Sankyo; grants to their institution from Pfizer, Macrogenics, and Genentech/Roche; consulting fees from AstraZeneca, Daiichi Sankyo, Genentech/Roche, Bristol Myers Squibb, Macrogenics, Taiho Oncology, and Seattle Genetics; honoraria from AstraZeneca; participation on a data safety monitoring or advisory board for Novartis and Merck; a leadership or fiduciary role in PureTech; and stock options in PureTech. YHP reports grants from MSD, Pfizer, Roche, AstraZeneca, Gencurix, NGeneBio, and Genome Insight; consulting fees from AstraZeneca, Pfizer, Eli Lilly, Bixink, MSD, Eisai, Roche, Daiichi Sankyo, Menarini, Gilead, and Novartis; payment for lectures, presentations, or educational events from AstraZeneca, Pfizer, Lilly, MSD, Roche, Daiichi Sankyo, and Novartis; support for attending meetings from Pfizer and Roche; participation on a data safety monitoring or advisory board for AstraZeneca, Pfizer, Roche, Gilead, and Novartis; and receipt of equipment or other services from Dong-A ST, Sanofi, Pfizer, and Roche. MDL reports payments for lectures or presentations from Eli Lilly, Novartis, Seagen, Takeda, Roche, Daiichi Sankyo, Tomalab, Gilead, Genetic, Menarini, and Sophos; support for attending meetings from Gilead, Novartis, Roche, and AstraZeneca; and participation on a data safety monitoring or advisory board for Pfizer, AstraZeneca, Sanofi, Seagen, Novartis, Ipsen, Roche, Pierre-Fabre, Daiichi Sankyo, and GSK. YM reports institutional grants from Daiichi Sankyo, Eisai, Chugai, MSD, Kyowa-Kirin, Eli Lilly, and Taiho; consulting fees from Daiichi Sankyo; and payments for lectures from Daiichi Sankyo, Chugai, Eisai, Eli Lilly, AstraZeneca, Pfizer, Taiho, and Kyowa-Kirin. AA reports institutional research funding from AstraZeneca; payment of advisory board fees from MSD, Gilead, AstraZeneca, and Roche; support for attending meetings from Novartis and Roche; and spousal shares from AstraZeneca. RY reports grants from Roche; consulting fees from Novartis, AstraZeneca, Eli Lilly, Roche, Medison, Pfizer, and Gilead; and payment for lectures or presentations from Novartis, AstraZeneca, Roche, Pfizer, and Eli Lilly. FPD reports grants from Fondation Belge Contre le Cancer; institutional payments from Roche, Pfizer, AstraZeneca, Eli Lilly, Novartis, Amgen, Daiichi Sankyo, Pierre-Fabre, Gilead, Seagen, and MSD; and support for attending meetings from Amgen, Roche, Teva, Pfizer, Daiichi Sankyo, AstraZeneca, Gilead, and MSD. TT reports payments for lectures from Daiichi Sankyo, Chugai, and Eli Lilly. AE is a full-time employee of Daiichi Sankyo and reports a restricted stock unit plan of Daiichi Sankyo Europe. S-BK reports institutional grants from Novartis, Sanofi, and DongKook Pharma; consulting fees from Novartis, AstraZeneca, Eli Lilly, Dae Hwa Pharm, ISU Abxis, and Daiichi Sankyo; payment for lectures from Novartis, AstraZeneca, Eli Lilly, Dae Hwa Pharm, ISU Abxis, and Daiichi Sankyo; a scientific co-chair role in ESMO Breast 2021–23 conferences; and stock in Genopeakes. MRB declares no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

After the initiation of veno-arterial extracorporeal membrane oxygenation (V-A ECMO) for hemodynamic support, patients often require vasopressor and inotropic medications to support their blood pressure and cardiac contractility. The vasoactive-inotropic score (VIS) is a standardized calculation of vasopressor and inotrope equivalence, which uses coefficients for each medication to calculate a total value. This study evaluated the association between the 30-day survival of patients receiving V-A ECMO support and the VIS calculated 24 h after ECMO cannulation (VIS24). This was a single-center, retrospective, observational cohort study. The median VIS24 of the entire cohort was 6.0, and was determined as a cutoff for comparison. Patients with a VIS24 < 6.0 were assigned to a group, and those with a VIS24 ≥ 6.0 were assigned to a second group. Patients with a VIS24 < 6.0 had higher 30-day survival than those with a VIS24 ≥ 6.0 (54.5% vs 41.4%; p  = 0.03). The group with a VIS24 < 6.0 also had significantly improved survival to decannulation of ECMO support; however, there was no difference in the survival to hospital discharge. We conducted a secondary analysis of quartiles and determined that individuals with a VIS24 > 11.4 had the lowest survival in the cohort. This finding may help identify patients with the lowest probability of 30-day survival in those receiving V-A ECMO for hemodynamic support., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Extracorporeal life support with venoarterial extracorporeal membrane oxygenation (VA-ECMO) is used to assist circulation in patients with severe cardiogenic shock or cardiac arrest. The vasoactive-inotropic score (VIS) is a standardized calculation of vasoactive medication support which uses coefficients for each medication that converts them to an equivalent value. The purpose of this study was to assess the VIS as an early prognostication tool for survival to decannulation patients on adult VA-ECMO support. This was a single-center, observational cohort study of adult patients who received VA-ECMO support compared based on their survival to decannulation. The primary endpoint was the VIS at hour 24 postcannulation. Among the 265 patients included in this study, 140 patients (52.8%) survived to decannulation of VA-ECMO. At 24 hours postcannulation, a lower VIS was observed in the group that survived decannulation (6.5 ± 7.5 vs. 12.3 ± 16.9; p < 0.001). Multivariate analysis performed also demonstrates an association between 24-hour VIS and survival to decannulation (odds ratio 0.95; 95% confidence interval, 0.91-0.95). This study suggests that the 24-hour VIS may be an early prognostic indicator in patients on VA-ECMO patients. http://links.lww.com/ASAIO/B39., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2023.)

Background: DESTINY-Breast01 (NCT03248492) is a phase II single-arm trial evaluating trastuzumab deruxtecan (T-DXd) in adults with human epidermal growth factor receptor 2-positive (HER2+) unresectable or metastatic breast cancer (u/mBC) who have received two or more prior anti-HER2 therapies., Objectives: Objectives were to explore approaches for estimating long-term overall survival (OS) with T-DXd from immature data (June 2020 data-cut; median follow-up 20.5 months), and compare predicted long-term outcomes with UK-recommended non-targeted therapies eribulin, capecitabine, and vinorelbine., Methods: Two methods were used to model T-DXd long-term OS: (1) applying a hazard ratio (HR) to the OS curve for another HER2 targeted therapy (third-line trastuzumab emtansine [T-DM1]) with longer trial follow-up; and (2) extrapolating T-DXd OS data directly. Comparator OS was based on direct extrapolation of published data (comparison with vinorelbine OS was not possible). Quality-adjusted life years (QALYs) were calculated using a previously published model of utility., Results: Both extrapolation methods demonstrated longer mean/median OS with T-DXd versus eribulin, and capecitabine (44.7/32.9 months [applying an HR to the T-DM1 OS curve]; 47.7/29.9 months [using direct extrapolation]; vs 11.3/9.2, and 17.8/13.6 months, respectively), translating to 2.3, 2.3, 0.6, and 0.9 discounted QALYs., Conclusion: Alternative methods produced consistent results, showing T-DXd is associated with substantial gains in OS and QALYs versus eribulin, and capecitabine. Modelled median OS results were similar to a later data-cut (median of 29.1 months, March 2021 data-cut). The modelling approach in which an HR was applied to the T-DM1 OS curve informed a submission to the National Institute for Health and Care Excellence., (© 2022. The Author(s).)