Ab Initio Calculation of the Lattice Distortions induced by Substitutional Ag- and Cu- Impurities in Alkali Halide Crystals

An ab initio study of the doping of alkali halide crystals (AX: A = Li, Na, K, Rb; X = F, Cl, Br, I) by ns2 anions (Ag- and Cu-) is presented. Large active clusters with 179 ions embedded in the surrounding crystalline lattice are considered in order to describe properly the lattice relaxation induced by the introduction of substitutional impurities. In all the cases considered, the lattice distortions imply the concerted movement of several shells of neighbors. The shell displacements are smaller for the smaller anion Cu-, as expected. The study of the family of rock-salt alkali halides (excepting CsF) allows us to extract trends that might be useful at a predictive level in the study of other impurity systems. Those trends are presented and discussed in terms of simple geometric arguments.Comment: LaTeX file. 8 pages, 3 EPS pictures. New version contains calculations of the energy of formation of the defects with model clusters of different size

Vibrational properties of the one-component σ\sigma phase

A structural model of a one-component $\sigma$-phase crystal has been constructed by means of molecular dynamics simulation. The phonon dispersion curves and the vibrational density of states were computed for this model. The dependence of the vibrational properties on the thermodynamical parameters was investigated. The vibrational density of states of the $\sigma$-phase structure is found to be similar to that of a one-component glass with icosahedral local order. On the basis of this comparison it is concluded that the $\sigma$ phase can be considered to be a good crystalline reference structure for this glass

Ixazomib as consolidation and maintenance versus observation in patients with relapsed multiple myeloma eligible for salvage autologous stem-cell transplantation (Myeloma XII [ACCoRD]): interim analysis of a multicentre, open-label, randomised, phase 3 trial

Background The efficacy of consolidation and maintenance in the context of salvage autologous haematopoietic stem-cell transplantation (HSCT) for relapsed multiple myeloma remains unclear. We aimed to assess whether consolidation after salvage autologous HSCT, using ixazomib, thalidomide, and dexamethasone, followed by maintenance with single agent ixazomib is superior to observation. Methods This is an interim analysis of Myeloma XII (ACCorD; referred to as ACCorD hereafter), an open-label, randomised, controlled, phase 3 trial done at 79 hospitals in the UK. Eligible patients were aged 18 years or older, had relapsed multiple myeloma with measurable disease, an ECOG performance status of 2 or less with adequate renal, hepatobiliary, pulmonary, and cardiac function, and required treatment for first progressive disease occurring at least 12 months after first autologous HSCT. In a first randomisation, patients were assigned (1:1) to receive either conventional autologous HSCT with melphalan or augmented autologous HSCT with melphalan and ixazomib. In the second randomisation, reported here, patients were assigned (1:1) to consolidation using ixazomib, thalidomide, and dexamethasone (oral ixazomib 4 mg per day on days 1, 8, and 15, oral thalidomide 100 mg per day on days 1–28, and oral dexamethasone 40 mg per day on days 1, 8, 15 and 22 of 28-day cycles), followed by maintenance with single agent ixazomib (oral ixazomib 4 mg per day on days 1, 8, and 15 of 28-day cycles until disease progression or intolerance), or observation. The primary endpoint was progression-free survival, analysed by intention-to-treat. Safety was analysed per-protocol. This study is registered with ISRCTN, ISRCTN10038996, and EudraCT, 2016-000905-35, and recruitment is complete. Findings Between Dec 12, 2017, and April 21, 2023, 206 patients entered the second randomisation (103 in the consolidation and maintenance group and 103 in the observation group). This prespecified interim analysis (data cutoff April 21, 2023), was done at a median follow-up of 27 months (IQR 13–38). Median progression-free survival was 20 months (95% CI 15–29) in the consolidation and maintenance group and 13 months (11–18) in the observation group (hazard ratio 0·55 [95% CI 0·39–0·78]; p=0·0006). Serious adverse events were reported in 29 (32%) of 92 patients in the consolidation and maintenance group compared with seven (7%) of 103 patients in the observation group. The most common serious adverse events were infections and infestations in both the consolidation and maintenance group and the observation group. The most common grade 3, 4, or 5 adverse events for patients in the consolidation and maintenance group were upper respiratory infection (seven [8%] of 92 patients). No deaths in the consolidation and maintenance group were deemed treatment related. Interpretation ACCorD provides evidence that an orally administered, deliverable, and tolerable post-salvage autologous HSCT treatment regimen can improve the durability of response for transplantation-eligible patients at first relapse. The findings are of relevance to patients who had durable disease control from autologous HSCT in the first line, representing a viable alternative to continuous parentally-administered relapse therapies. Funding Cancer Research UK, Takeda Oncology

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries