The use and impact of digital COVID-19 tracking in adult social care: a prospective cohort study of care homes in Greater Manchester

Background: To support proactive care during the coronavirus pandemic, a digital COVID-19 symptom tracker was deployed in Greater Manchester (UK) care homes. This study aimed to understand what factors were associated with the post-uptake use of the tracker and whether the tracker had any effects in controlling the spread of COVID-19. Methods: Daily data on COVID-19, tracker uptake and use, and other key indicators such as staffing levels, the number of staff self-isolating, availability of personal protective equipment, bed occupancy levels, and any problems in accepting new residents were analysed for 547 care homes across Greater Manchester for the period April 2020 to April 2021. Differences in tracker use across local authorities, types of care homes, and over time were assessed using correlated effects logistic regressions. Differences in numbers of COVID-19 cases in homes adopting versus not adopting the tracker were compared via event design difference-in-difference estimations. Results: Homes adopting the tracker used it on 44% of days post-adoption. Use decreased by 88% after one year of uptake (odds ratio 0.12; 95% confidence interval 0.06-0.28). Use was highest in the locality initiating the project (odds ratio 31.73; 95% CI 3.76-268.05). Care homes owned by a chain had lower use (odds ratio 0.30; 95% CI 0.14-0.63 versus single ownership care homes), and use was not associated with COVID-19 or staffing levels. Tracker uptake had no impact on controlling COVID-19 spread. Staff self-isolating and local area COVID-19 cases were positively associated with lagged COVID-19 spread in care homes (relative risks 1.29; 1.2-1.4 and 1.05; 1.0-1.1, respectively). Conclusions: The use of the COVID-19 symptom tracker in care homes was not maintained except in Locality 1 and did not appear to reduce the COVID-19 spread. COVID-19 cases in care homes were mainly driven by care home local-area COVID-19 cases and infections among the staff members. Digital deterioration trackers should be co-produced with care home staff, and local authorities should provide long-term support in their adoption and use

The role of care home fees in the public costs and distributional effects of potential reforms to care home funding for older people in England

In England, Local Authorities (LAs) contribute to the care home fees of two-thirds of care home residents aged 65+ who pass a means test. LAs typically pay fees below those faced by residents excluded from state support. Most proposals for reform of the means test would increase the proportion of residents entitled to state support. If care homes receive the LA fee for more residents, they might increase fees for any remaining self-funders. Alternatively, the LA fee might have to rise. We use two linked simulation models to examine how alternative assumptions on post-reform fees affect projected public costs and financial gains to residents of three potential reforms to the means test. Raising the LA fee rate to maintain income per resident would increase the projected public cost of the reforms by between 22% and 72% in the base year. It would reduce the average gain to care home residents by between 8% and 12%. Raising post-reform fees for remaining self-funders or requiring pre-reform self-funders to meet the difference between the LA and self-funder fees, reduces the gains to residents by 28-37%. For one reform, residents in the highest income quintile would face losses if the self-funder fee rises. © 2012 Cambridge University Press

3D printed lattice metal structures for enhanced heat transfer in latent heat storage systems

The low thermal conductivity of Phase Change Materials (PCMs), e.g., paraffin waxes, is one of the main drawbacks of latent heat storage, especially when fast charging and discharging cycles are required. The introduction of highly conductive fillers in the PCM matrix may be an effective solution; however, it is difficult to grant their stable and homogeneous dispersion, which therefore limits the resulting enhancement of the overall thermal conductivity. Metal 3D printing or additive manufacturing, instead, allows to manufacture complex geometries with precise patterns, therefore allowing the design of optimal paths for heat conduction within the PCM. In this work, a device-scale latent heat storage system operating at medium temperatures (similar to 90 celcius) was manufactured and characterized. Its innovative design relies on a 3D Cartesian metal lattice, fabricated via laser powder bed fusion, to achieve higher specific power densities. Numerical and experimental tests demonstrated remarkable specific power (approximately 714 +/- 17 W kg-1 and 1310 +/- 48 W kg-1 during heat charge and discharge, respectively). Moreover, the device performance remained stable over multiple charging and discharging cycles. Finally, simulation results were used to infer general design guidelines to further enhance the device performance. This work aims at promoting the use of metal additive manufacturing to design efficient and responsive thermal energy storage units for medium-sized applications, such as in the automotive sector (e.g. speed up of the engine warm up or as an auxiliary for other enhanced thermal management strategies)

Constitutive IP₃ signaling underlies the sensitivity of B-cell cancers to the Bcl-2/IP₃ receptor disruptor BIRD-2

Anti-apoptotic Bcl-2 proteins are upregulated in different cancers, including diffuse large B-cell lymphoma (DLBCL) and chronic lymphocytic leukemia (CLL), enabling survival by inhibiting pro-apoptotic Bcl-2-family members and inositol 1,4,5-trisphosphate (IP3) receptor (IP3R)-mediated Ca2+-signaling. A peptide tool (Bcl-2/IP3R Disruptor-2; BIRD-2) was developed to abrogate the interaction of Bcl-2 with IP3Rs by targeting Bcl-2′s BH4 domain. BIRD-2 triggers cell death in primary CLL cells and in DLBCL cell lines. Particularly, DLBCL cells with high levels of IP3R2 were sensitive to BIRD-2. Here, we report that BIRD-2-induced cell death in DLBCL cells does not only depend on high IP3R2-expression levels, but also on constitutive IP3 signaling, downstream of the tonically active B-cell receptor. The basal Ca2+ level in SU-DHL-4 DLBCL cells was significantly elevated due to the constitutive IP3 production. This constitutive IP3 signaling fulfilled a pro-survival role, since inhibition of phospholipase C (PLC) using U73122 (2.5 µM) caused cell death in SU-DHL-4 cells. Milder inhibition of IP3 signaling using a lower U73122 concentration (1 µM) or expression of an IP3 sponge suppressed both BIRD-2-induced Ca2+ elevation and apoptosis in SU-DHL-4 cells. Basal PLC/IP3 signaling also fulfilled a pro-survival role in other DLBCL cell lines, including Karpas 422, RI-1 and SU-DHL-6 cells, whereas PLC inhibition protected these cells against BIRD-2-evoked apoptosis. Finally, U73122 treatment also suppressed BIRD-2-induced cell death in primary CLL, both in unsupported systems and in co-cultures with CD40L-expressing fibroblasts. Thus, constitutive IP3 signaling in lymphoma and leukemia cells is not only important for cancer cell survival, but also represents a vulnerability, rendering cancer cells dependent on Bcl-2 to limit IP3R activity. BIRD-2 seems to switch constitutive IP3 signaling from pro-survival into pro-death, presenting a plausible therapeutic strategy

Nonequilibrium molecular dynamics simulations of nanoconfined fluids at solidliquid interfaces

We investigate the hydrodynamic properties of a Lennard-Jones fluid confined to a nanochannel using molecular dynamics simulations. For channels of different widths and hydrophilic-hydrophobic surface wetting properties, profiles of the fluid density, stress, and viscosity across the channel are obtained and analysed. In particular, we propose a linear relationship between the density and viscosity in confined and strongly inhomogeneous nanofluidic flows. The range of validity of this relationship is explored in the context of coarse grained models such as dynamic density functional-theory

Proteomics of synapse

Large-scale phosphoproteome analysis on synaptosome and preparation of post-synaptic density (PSD) were investigated. It was found that protein phosphor is a common event in the synapse, which is consistent with the presence of diverse classes of kinases and phosphatases in the synapse. Synaptic proteomics analysis required the purification of subcellular organelles from the brain regions of interest. Multiple steps of discontinuous density gradient ultra-centrifugation were employed to enrich the distinct organelles. Two-dimensional gel electrophoresis was used to separate and quantify proteins, including post-translational modified forms, from synaptic structures. It was observed that proteomic analysis of the synaptic vesicle identified 36 proteins, including seven integral membrane proteins and vesicle regulatory proteins

Risk of SARS-CoV-2 infection and subsequent hospital admission and death at different time intervals since first dose of COVID-19 vaccine administration, Italy, 27 December 2020 to mid-April 2021

To assess the real-world impact of vaccines on COVID-19 related outcomes, we analysed data from over 7 million recipients of at least one COVID-19 vaccine dose in Italy. Taking 0–14 days post-first dose as reference, the SARS-CoV-2 infection risk subsequently decreased, reaching a reduction by 78% (incidence rate ratios (IRR): 0.22; 95% CI: 0.21–0.24) 43–49 days post-first dose. Similarly, hospitalisation and death risks decreased, with 89% (IRR: 0.11; 95% CI: 0.09–0.15) and 93% (IRR: 0.07; 95% CI: 0.04–0.11) reductions 36–42 days post-first dose. Our results support ongoing vaccination campaigns

Excess deaths from COVID-19 and other causes by region, neighbourhood deprivation level and place of death during the first 30 weeks of the pandemic in England and Wales: A retrospective registry study

Background: Excess deaths during the COVID-19 pandemic compared with those expected from historical trends have been unequally distributed, both geographically and socioeconomically. Not all excess deaths have been directly related to COVID-19 infection. We investigated geographical and socioeconomic patterns in excess deaths for major groups of underlying causes during the pandemic. Methods: Weekly mortality data from 27/12/2014 to 2/10/2020 for England and Wales were obtained from the Office of National Statistics. Negative binomial regressions were used to model death counts based on pre-pandemic trends for deaths caused directly by COVID-19 (and other respiratory causes) and those caused indirectly by it (cardiovascular disease or diabetes, cancers, and all other indirect causes) over the first 30 weeks of the pandemic (7/3/2020–2/10/2020). Findings: There were 62,321 (95% CI: 58,849 to 65,793) excess deaths in England and Wales in the first 30 weeks of the pandemic. Of these, 46,221 (95% CI: 45,439 to 47,003) were attributable to respiratory causes, including COVID-19, and 16,100 (95% CI: 13,410 to 18,790) to other causes. Rates of all-cause excess mortality ranged from 78 per 100,000 in the South West of England and in Wales to 130 per 100,000 in the West Midlands; and from 93 per 100,000 in the most affluent fifth of areas to 124 per 100,000 in the most deprived. The most deprived areas had the highest rates of death attributable to COVID-19 and other indirect deaths, but there was no socioeconomic gradient for excess deaths from cardiovascular disease/diabetes and cancer. Interpretation: During the first 30 weeks of the COVID-19 pandemic there was significant geographic and socioeconomic variation in excess deaths for respiratory causes, but not for cardiovascular disease, diabetes and cancer. Pandemic recovery plans, including vaccination programmes, should take account of individual characteristics including health, socioeconomic status and place of residence. Funding: None

CARFILZOMIB, LENALIDOMIDE AND DEXAMETHASONE IN RELAPSED/REFRACTORY MULTIPLE MYELOMA PATIENTS: THE REAL LIFE EXPERIENCE OF RETE EMATOLOGICA PUGLIESE (REP)

Background: Carfilzomib, lenalidomide and dexamethasone (KRd) has been approved for the treatment of relapsed and refractory multiple myeloma (RRMM) based on ASPIRE clinical trial. However, its effectiveness and safety profile in real clinical practice should be further assessed. Aims: We retrospectively evaluated 120 consecutive RRMM patients treated with KRd, in 9 hematology departments of Rete Ematologica Pugliese (REP), with the aim to evaluate the efficacy and safety with KRd treatment in a real world setting. Methods: Between December of 2015 and August 2018,120 RRMM patients were analyzed.The patients’ baseline characteristics are presented in Table 1. Median patient’s age was 66 years and 41 patients(34%) were older than 70 years. The median number of previous treatment lines was 1 (range 1–11). The 94% of the patients had been already treated with bortezomib-based regimens and 33% with both lenalidomide- and bortezomib-based regimens. Moreover, half of the patients (52%) had a previous autologous stem cell transplant. The median time from the diagnosis to start of treatment with KRd was 40 months (range 5–295) and 30 patients were treated with KRd early (≤18 months from diagnosis).Disease status at the start of treatment with KRd was refractory in 33 patients(29%) and 13 patients(12%) were refractory to lenalidomide. Twenty-four patients(21%) were refractory at last therapy before KRd enrollment. Results: The overall response rate (ORR) was 84%(n = 93),with 23%(25) complete response (CR) and 50%(55) very good partial response(VGPR).The median duration of response was 12,9 months (range, 3,33– 27,7). ORR was higher in patients relapsed after a previous autologous transplant (ASCT;56% vs 37% in those relapsed without prior ASCT;p 0,05).Patients treated in late relapse had a better ORR (44%) vs those in early relapse (19%; p 0,02). After a median follow-up of 13,4 months, median PFS was not reached (NR) and 2y-PFS was 61%, Figure 1. PFS was longer in responding patients (achieving at least PR) to those with less than PR (median PFS NR vs 4,9 months;p 0,0001).Median PFS in patients relapsed after a prior ASCT was NR vs 20 months in those without prior ASCT, (p 0,002).Patients achieving ASCT after KRD had a better PFS in confront to those without ASCT (median NR vs 9 months, p 0,001).Several baseline patient characteristics, such as the III ISS scoring, older age, prior exposure to lenalidomide and early relapse were found to negatively impact PFS.Twenty-eight patients(24%) performed 4 KRd cycles as bridge treatment to ASCT. The 64% of patients reached a VGPR and 67% received ASCT, with 9 upgraded from VGPR to complete response (CR) after ASCT.The treatment discontinuation rate due to adverse events (AEs) was 13%, most commonly related to lenalidomide(8%). KRd dose reduction was necessary in 11% of patients (2,5% for carfilzomib and 8% for lenalidomide).The most frequent AE was neutropenia(43%) and anemia (41%). Infections occurred in 10% of patients.Adverse Cardiovascular toxicity (Atrial fibrillation and pulmonary hypertension)occurred in 8% of patients. Summary/Conclusion: Our analysis confirmed that KRd is effective in RRMM patients. It is well tolerated and applicable to the majority of patients outside clinical trials. A longer PFS was shown in patients 24th Congress of the European Hematology Association 276 | 2019;3:S1 achieving at least a partial response (PR), relapsing after previous ASCT and in those with the possibility to perform ASCT after KRd treatment. Accordingly,KRd should be used as an optimal bridge regimen to ASCT. Previous ASCT should not hamper the option for KRd therap