Data Snapshot Research Articles

MDB-KCP: persistence framework of in-memory database with CRIU-based container checkpoint in Kubernetes

As the demand for container technology and platforms increases due to the efficiency of IT resources, various workloads are being containerized. Although there are efforts to integrate various workloads into Kubernetes, the most widely used container platform today, the nature of containers makes it challenging to support persistence for memory-centric workloads like in-memory databases. In this paper, we discuss the drawbacks of one of the persistence support methods used for in-memory databases in a Kubernetes environment, namely, the data snapshot. To address these issues, we propose a compromise solution of using container checkpoints. Through this approach, we can perform checkpointing without incurring additional memory usage due to CoW, which is a problem in fork-based data snapshots during snapshot creation. Additionally, container checkpointing induces up to 7.1 times less downtime compared to the main process-based data snapshot. Furthermore, during database recovery, it is possible to achieve up to 11.3 times faster recovery compared to the data snapshot method.

THU173 Subanalysis By Tanner Stage In Phase 3 Trials In Children And Adolescents With Growth Hormone Deficiency Treated With Lonapegsomatropin

Abstract Disclosure: P. Hofman: Speaker; Self; Novo Nordisk, Eli Lilly & Company. P.S. Thornton: Research Investigator; Self; Ascendis, Pfizer, Inc., Opko, Zealand, Rezolute, Spruce. Other; Self; Johnson &Johnson, Rezolute. U.M. Nadgir: None. P. Saenger: None. E. Chertok: None. E.M. Aghajanova: Speaker; Self; Berlin Hemi Menarini. M. Mao: Employee; Self; Ascendis Pharma. C. Zhao: Employee; Self; Ascendis Pharma. M.R. Ochoa-Maya: Employee; Self; Ascendis Pharma. A. Komirenko: Employee; Self; Ascendis Pharma. A.D. Shu: Employee; Self; Ascendis Pharma. A.K. Maniatis: Advisory Board Member; Self; Novo Nordisk, Ascendis Pharma, Pfizer, Inc. Consulting Fee; Self; Novo Nordisk, Ascendis Pharma. Research Investigator; Self; Novo Nordisk, Pfizer, Inc., OPKO, Ascendis Pharma. Speaker; Self; Novo Nordisk, Ascendis Pharma. Background: Historically, the treatment paradigm in pediatric growth hormone deficiency (GHD) has been to consider increased doses (up to 0.7 mg hGH/kg/week) later in pubertal development to maximize growth outcomes, although this is not a routine recommendation (Mauras et al. JCEM. 2000;85(10):3653-3660, Grimberg et al. Horm Res Paeds. 2016;86(6):361-397). The enliGHten open-label extension trial of once-weekly lonapegsomatropin provided the opportunity to evaluate dosing, efficacy, and safety outcomes in a group of children that includes more advanced Tanner Stages. Lonapegsomatropin (TransCon hGH), a once-weekly prodrug of somatropin approved for the treatment of pediatric GHD by the FDA and EMA, uses TransCon technology to transiently link a parent drug to an inert carrier. In the pivotal phase 3 heiGHt trial, lonapegsomatropin demonstrated noninferior and superior annualized height velocity and a comparable safety profile to daily somatropin in children with GHD. The current analysis explores IGF-1 levels, dose adjustments, and height outcomes by Tanner Stage. Methods: Three phase 3 trials assessed safety and efficacy of lonapegsomatropin: heiGHt (treatment-naïve trial), fliGHt (switch trial), and enliGHten (open-label extension trial). Participants treated in the 3 phase 3 trials were included in this analysis (data snapshot date, September 1, 2021). Data were analyzed by the most recent Tanner Stage at time of assessment in 3 groups: Stage 1 and 2; Stage 3; and Stage 4 and 5. Association between Tanner Stage and IGF-1 SDS measurements, lonapegsomatropin dose, and height SDS were examined using mixed repeated models with Tanner stage as time-varying covariate. Relationship between dose reduction and change in IGF-1 SDS was summarized by Tanner stage. Results: With a mean follow-up of 157 weeks (N=306) on lonapegsomatropin treatment, the analysis showed that later Tanner Stages (3, 4-5) were correlated with higher average IGF-1 SDS (versus Stages 1-2). There was a small difference in lonapegsomatropin dose across Tanner Stage groups, with participants in Stages 4-5 receiving the lowest mean dose (0.19 mg hGH/kg/wk) compared with Stages 1-2 (0.23 mg hGH/kg/wk) or Stage 3 (0.22 mg hGH/kg/wk). Among patients with dose reduction, a decrease of lonapegsomatropin of 0.02 mg hGH/kg corresponded to a consistent drop in average IGF-1 SDS across all Tanner Stages (overall, 0.16 SDS; Stages 1-2, 0.21 SDS; Stage 3, 0.16 SDS; Stages 4-5, 0.21 SDS). Participants across all subgroups experienced continued growth as expected over time. Conclusions: This analysis showed that it was possible to maintain consistent height SDS improvements in children and adolescents in Tanner Stages 3-5 without an increase in the mean lonapegsomatropin dose. Lonapegsomatropin dose reductions resulted in predictable linear IGF-1 decreases across Tanner Stages. Presentation: Thursday, June 15, 2023

REVIEW OF THE INTRODUCTION OF WHOLE GENOME SEQUENCING AS NHS STANDARD OF CARE FOR BRAIN TUMOUR PATIENTS AT QUEEN ELIZABETH HOSPITAL BIRMINGHAM, UK

Abstract AIMS Describe delays in the NHS pathway from initial consent for whole genome sequencing (WGS) to delivery of the final WGS report (WGS-R) to the treating oncologist. Review number of patients with mutations that inform, diagnosis, prognosis or treatment. METHOD Prospective audit of time to key stages along WGS pathway and review of final WGS-R. RESULTS WGS pathway and process: Data snapshot at 24/02/2023 showed 96 patients consented for WGS: 12/96 awaiting surgery; 41/96 awaiting GTAB discussion; 1/96 WGS sample used for histopathological diagnosis, 1/96 ineligible. 41/96 WGS results discussed at a GTAB meeting; 39/44 with complete WGS-R sent to the treating oncologist, including discussion at the local neuro-oncology multi-disciplinary team meeting. Median time from consent to final WGS-R was 225 days (range 145-567). WGS results: 4 patients with glioblastoma (GBM) have RB1 variant, associated with improved progression-free and overall survival (Dono et al 2021). 10 patients had clinically actionable mutations with recommended trials or compassionate-use drugs. 1/10 patient with GBM and High Tumour Mutational Burden who completed standard of care (SOC) treatment has commenced anti-PD1 immunotherapy (Nivolumab; Goodman et al 2017). 5/10 patients are currently on SOC treatment, 3/10 had deteriorated and 1/10 were deceased at time of WGS-R. Excellent concordance of WGS data with SOC genetic/immunohistochemistry testing. No germline mutations identified. CONCLUSIONS Nearly a third of patients had genetic variants that may have the potential to inform future clinical management. Further investment in the WGS pathway is required to deliver timely results to allow application of precision medicine for brain cancer patients.

Multiscale Representation of Radar Echo Data Retrieved through Deep Learning from Numerical Model Simulations and Satellite Images

Radar reflectivity data snapshot fine-grained atmospheric variations that cannot be represented well by numerical weather prediction models or satellites, which poses a limit for nowcasts based on model–data fusion techniques. Here, we reveal a multiscale representation (MSR) of the atmosphere by reconstructing the radar echoes from the Weather Research and Forecasting (WRF) model simulations and the Himawari-8 satellite products using U-Net deep networks. Our reconstructions generated the echoes well in terms of patterns, locations, and intensities with a root mean square error (RMSE) of 5.38 dBZ. We find stratified features in this MSR, with small-scale patterns such as echo intensities sensitive to the WRF-simulated dynamic and thermodynamic variables and with larger-scale information about shapes and locations mainly captured from satellite images. Such MSRs with physical interpretations may inspire innovative model–data fusion methods that could overcome the conventional limits of nowcasting.

Uncertainty transmission of fluid data upon proper orthogonal decompositions

Proper orthogonal decomposition (POD) serves as a principal approach for modal analysis and reduced-order modeling of complex flows. The method works robustly with most types of fluid data and is fundamentally trusted. While, in reality, one has to discern the input spatiotemporal data as passively contaminated globally or locally. To understand this problem, we formulate the relation for uncertainty transmission from input data to individual POD modes. We incorporate a statistical model of data contamination, which can be independently established based on experimental measurements or credible experiences. The contamination is not necessarily a Gaussian white noise, but a structural or gusty modification of the data. Through case studies, we observe a general decaying trend of uncertainty toward higher modes. The uncertainty originates from twofold: self-correlation and cross correlation of the contamination terms, where the latter could become less influential, given the narrow correlation width measured in experiments. Mathematically, the self-correlation is determined by the inner product of the data snapshot and the mode itself. Therefore, the similarity between the input data and the resulting POD modes becomes a critical and intuitive indicator when quantifying the uncertainty. A scaling law is shown to be applicable for self-correlation that promotes fast quantification on sparse grids.

Roles, Values, and Qualifications in Transition: An Initial Data Snapshot of Post- secondary Journalism Educators in Canada and Their Perspectives on Where Journalism is Going

Roles, Values, and Qualifications in Transition: An Initial Data Snapshot of Post- secondary Journalism Educators in Canada and Their Perspectives on Where Journalism is Going

Russian Randomized Trial to Select Optimal Antibiotic Prophylaxis in Radical Cystectomy: Initial Results of MACS-TRIAL (NCT05392634)

Introduction. The key treatment for high-risk non-invasive bladder tumor or invasive urothelial cancer remains radical cystectomy (RCE), which provides the best survival rates. At the same time, the incidence of infectious complications in a number of studies reaches 33%, which in most cases causes repeated hospitalizations and disrupts the Enhanced Recovery After Surgery (ERAS) guidelines. Therefore, research into effective alternations of antibiotic prophylaxis remains relevant.Materials and methods. The MACS trial is a Russian Phase 3 study with a prospective randomized set of participants to assess the incidence of infectious complications after RCE in the context of the ERAS guidelines (intermediate data snapshot after including 39% of the data). Detailed inclusion and exclusion criteria are published on ClinicalTrials. gov, ID – NCT05392634. The study has been approved by the Local Ethics Committee, No. 1/129 of April 28, 2022. Statistical data processing was performed with StatPlus:Mac LE.Results and discussion. 36 patients were included in the study (39% of the expected sample). For the period from May 30, 2022 to February 01, 2023. A heterotopic Bricker reservoir was formed intracorporeally in 83.3% of cases (30/36), an orthotopic J-pouch reservoir was created in 13.8% of cases (5/36) and in 2.9% of cases (1/36) the urodereating stage was completed with ureteral clipping. No significant differences were revealed in urine bacterial contamination before surgery. However, in group A, the incidence of positive bacterial cultures, when the ureteric intubators were removed, was 2-fold higher than in the prolonged antibiotic therapy group: 7/14 cases (50.0%) and 3/12 cases (25.0%), respectively. In group B, the risk of complications in the prolonged antibiotic therapy group reduced by 47% within 30 days after RCE (HR 0.53 (95CI %: 0.21-1.32).Conclusion. An intermediate data snapshot in MACS study revealed that RCE was associated with a high risk of early postoperative infectious complications. The prognostic significance of systemic inflammation indices as predictors of infectious complications subject to further evaluation in the remaining 61% of cases.

2021 PennsylvaniaPatient Safety Reporting: Updated Rates for Acute Care Event Report

In the article we published in June 2022 on patient safety trends in 2021,1 reporting rates and fall rates for 2021 were calculated based on Q1 and Q2 only, as denominator data for Q3 and Q4 were not yet available. Given that the COVID-19 pandemic has disrupted reliable forecasting in healthcare,2 we did not forecast rates for Q3 and Q4 in our June 2022 article. This data snapshot provides the complete rates for 2021 now that we have obtained all relevant data.

RF26 | PMON332 Safety and Efficacy of Treatment with Lonapegsomatropin in Children with Growth Hormone Deficiency at Week 130 in the enliGHten Trial

Abstract Background Once-weekly lonapegsomatropin (TransCon hGH) is a long-acting prodrug of somatropin, recently approved for the treatment of pediatric growth hormone deficiency (GHD) by the US FDA. In the pivotal 52-week phase 3 heiGHt trial and the 26-week fliGHt trial, lonapegsomatropin demonstrated safety and efficacy in both treatment-naïve and treatment-experienced children with GHD. Methods Results are reported from Week 130 (data snapshot date: September 01, 2021) from the open-label extension trial enliGHten. Upon entry into enliGHten, all participants received lonapegsomatropin via vial/syringe, with subsequent switch to TransCon hGH Auto-Injector when available. Results A total of 298 participants (98% of parent trials) continued from the heiGHt or fliGHt trials into enliGHten. At Week 130, 36 participants had completed the trial and 248 participants remain enrolled. The height standard deviation score (SDS) mean (standard deviation [SD]) at Week 130 was -0.64 (0.85) compared with baseline value of -1.56 (0.88) at the start of enliGHten. Participants continued to approach the average parental height SDS mean (SD) of -0.39 (0.77). The annualized height velocity mean (SD) at Week 130 was 9.32 cm/year (0.45). Average IGF-1 SDS mean (SD) at Week 130 was 1.46 (1.18) compared with 0.52 (1.58) at enliGHten baseline. For the 36 participants who had completed the trial, 14 had reached bone age of >14 years (girls) or >16 years (boys), and 24 had completed the study based on investigator judgement that treatment for growth hormone deficiency was no longer necessary. The difference between mean (SD) height SDS at last visit and average parental height SDS was -0.05 (0.75) for the 36 completers, and 61.1% of these participants had met or exceeded the average parental height SDS. The mean (SD) total duration of hGH treatment for participants who completed the trial (including daily treatment and lonapegsomatropin) was 3.53 (0.88) years, and the mean (SD) duration of treatment with lonapegsomatropin was 2.20 (0.66). With continued lonapegsomatropin treatment, the AE profile remained consistent with what was observed in the parent trials, with no new safety signals. Conclusions Children and adolescents treated with lonapegsomatropin showed continued improvement of height SDS through their 3rd year of therapy. Lonapegsomatropin continued to demonstrate a safety profile comparable to that of daily somatropin therapy. Presentation: Monday, June 13, 2022 12:30 p.m. - 12:35 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Clinical outcomes in patients with atrial fibrillation with or without concomitant diabetes after two years of edoxaban treatment: ETNA-AF-Europe registry

Abstract Background/Introduction Concomitant diabetes mellitus (DM) in patients with atrial fibrillation (AF) has been associated with a higher risk of stroke/systemic embolic events (SEE), and higher mortality. Purpose To evaluate effectiveness and safety outcomes in AF patients with different types of concomitant DM vs those without concomitant DM after 2 years of edoxaban treatment in a sub-analysis of the prospective ETNA-AF-Europe registry. Methods Patients with AF who received edoxaban once daily were enrolled across 825 centres in 10 European countries. This sub-analysis is based on a data snapshot from 26th October 2020. Patients were grouped by DM status (with or without DM; insulin-treated or non-insulin-treated DM). Baseline characteristics are summarised descriptively. Kaplan-Meier (KM) survival curves of outcomes were constructed; annualised event rates (AERs; %/year) and comparisons between patients with or without DM by univariate analysis are presented. Comparisons of patients with insulin- vs non-insulin-treated DM were made by multivariate analysis adjusted for HbA1c. Results Patients' demographics and baseline characteristics are shown in Table 1. Of 13,133 patients with AF, 2885 (22.0%) had DM. Among patients with DM, 2756 (95.6%) received treatment: 605 (22.0%) with insulin and 2151 (78.0%) with non-insulin treatments. KM curves for effectiveness and safety outcomes are shown in Figure 1. AERs (%/year) of ischaemic stroke/transient ischaemic attack (TIA)/SEE were 0.86% in patients with AF and no DM, 0.87% with non-insulin-treated DM (p=0.9216 vs no DM) and 1.81% with insulin-treated DM (p=0.0022 vs no DM; p=0.0014 vs non-insulin-treated DM). AERs of myocardial infarction (MI) were 0.40%, 0.43% (p=0.7454 vs no DM), and 1.04% (p=0.0033 vs no DM) respectively; of major bleeding were 0.90%, 1.10% (p=0.2427 vs no DM), and 1.71% (p=0.0106 vs no DM), respectively; and of all-cause death were 3.36%, 5.02% (p<0.0001 vs no DM), and 8.91% (p<0.0001 vs no DM) respectively. In a multivariate analysis of DM patients adjusted for HbA1c (patients with AF and DM with HbA1c measured, n=1869), patients with AF and insulin-treated DM had a higher risk of stroke/TIA/SEE (HbA1c adjusted HR [95% CI]: 2.13 [1.12–4.05], p=0.0205) and all-cause death (1.83 [1.35–2.49], p=0.0001) vs those with non-insulin-treated DM; no significant difference in the risk of MI (2.10 [0.78–5.66], p=0.1448) or major bleeding (1.81 [0.95–3.44], p=0.0706) was detected between the groups. Conclusion In patients with AF and DM, risk of stroke/TIA/SEE, MI and major bleeding was confined to insulin-treated DM patients only. These patients also had poorer survival rates vs those without DM and those with non-insulin-treated DM, reinforcing previously published data showing a strong association between insulin treatment and poorer outcomes, and a mild/absent association between non-insulin treatments and poorer outcomes in patients with AF and DM. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): This research was funded by Daiichi Sankyo Europe.

Two-year outcomes of patients with atrial fibrillation and heart failure: the ETNA-AF-Europe registry

Abstract Background Heart failure (HF) is an established risk factor for stroke and systemic embolic events (SEE) in subjects with atrial fibrillation (AF), but it is debated whether this risk varies according to left ventricular ejection fraction (LVEF). Methods We investigated the impact of HF in the ETNA-AF-Europe registry, a prospective, multi-centre, post-authorisation, observational study enrolling patients treated with edoxaban for AF in 825 sites from 10 European countries. This 2-year follow-up analysis is based on a data snapshot from 26 October 2020. HF was defined as a) history of HF or b) ischaemic cardiomyopathy or c) EF <40% or d) dyspnoea not due to chronic obstructive pulmonary disease together with ≥1 of the following: ischaemic heart disease, valvular heart disease, or hypertension treated with ≥3 drugs. Patients' characteristics are summarised descriptively and clinical outcomes are reported as annualised event rates. The hazard ratio (HR) with 95% confidence intervals (CI) for the association of HF with the outcomes was assessed in Cox regression models with stepwise variable selection. Results Of the 13,133 patients, 1,854 (14.1%) had HF; LVEF was available for 1,489 (80.3%), and was <40% in 671 (43.9%) and ≥40% in 857 (56.1%). Patients with HF were more often men and slightly older than those without (Table 1). As expected, they also had more cardiovascular (CV) comorbidities and higher CHA2DS2-VASC and, to a lesser extent, HAS-BLED scores (Table 1). At the end of the 2-year follow-up, the rates of ischaemic stroke/transient ischaemic attack (TIA)/SEE, major bleeding, intracranial haemorrhage (ICH), CV death, and all-cause death were higher in patients with than without HF (Figure 1). When patients with HF were categorized according to LVEF, ischaemic stroke/TIA/SEE was more frequent in those with LVEF ≥40% vs those with LVEF <40%. By contrast, more patients with LVEF <40% died due to any as well as CV causes. The rates of major bleeding and ICH were comparable between the two subgroups (Figure 1). Univariable Cox regression analysis confirmed the association of HF with major bleeding (HR 2.01, 95% CI [1.49–2.71]) and all-cause death (2.62 [2.28–3.02]), but not with ischaemic stroke/TIA/SEE (1.06 [0.72–1.55]). The results were consistent when LVEF was taken into account: the HRs for LVEF <40% or LVEF ≥40%, respectively, were 1.60 (0.99–2.60) and 1.55 (1.02–2.38) for major bleeding, 2.11 (1.69–2.63) and 1.59 (1.28–1.97) for all-cause death, and 0.66 (0.31–1.41) and 1.19 (0.71–1.98) for ischaemic stroke/TIA/SEE. Conclusions In this real-world, large cohort of patients with AF on edoxaban, those with HF at baseline faced more ischaemic, bleeding, and death events, and having HF increased the risk of major bleeding and death, with no differences according to LVEF. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): This research was funded by Daiichi Sankyo Europe.

Graphic Medicine as a Wake-up Call to Stand Against Female Genital Mutilation in Egypt

FGM, Female Genital Mutilation, is one of the most prevalent types of violence against girls and women in Egypt. Despite its horrific short- and long-term physical and psychological complications, according to UNICEF data reports, FGM remains widely practised against girls and women aged 15-49 in around 30 countries in Africa and Asia (UNICEF Egypt Data Snapshot, 2019). Non-medical, primarily, social and cultural beliefs that are associated with girls’ and women’s chastity, marriageability, hygiene and honour continue to control the lives of millions of them and, in some cases, lead to their death. November 25, 2021 marked the 30th anniversary of the global 16 days campaign of activism which was launched by the Centre for Women’s Leadership to raise awareness about violence against women worldwide. In Egypt, this year, among several events that commemorate the anniversary, Care Egypt Foundation in collaboration with the United Nations Population Fund (UNFPA) and the National Committee for the Eradication of Female Genital Mutilation (NCEFGM), launched a social media campaign against FGM entitled “My Story with Genital Mutilation” (Care Egypt, 2021). The campaign’s team gathered eight real-life stories of Egyptian women survivors and collaborated with artist Noran Fikri who drew the graphic artwork. In this research project, I argue that the aim of choosing graphic drawings for that campaign is twofold: 1) drawing real-life stories of Egyptian FGM survivors empowers thousands of girls/women to break their silence, and report about similar practices which may prevent potential victims from undergoing such abuse; 2) this campaign aims to reach large numbers of social platform users, to make FGM everyone’s problem in Egypt, in the hope of shifting the narrative from chiefly raising awareness about performing such violent practices into inspiring mainly not Non-Government Organizations, lawmakers or national officials but individuals—whether directly harmed or not—to take an action against FGM. I also suggest that this eight-graphic-stories collection is a representation of a graphic medicine movement in Egypt. Coined in 2010 by Ian Williams, Graphic Medicine is “the intersection of the medium of comics and the discourse of healthcare… a community where many people have found their voice” (Czerwiec et al, 2015, p. 1). The graphic form lends a fresh perspective on FGM survivors’ personal physical, psychological and mental suffering. It softly invites other women survivors to share their stories. Since it is a social media campaign, each of these eight very short stories is illustrated in a one-page graphic artwork, in a short, quick yet shocking and horrifying emotion-packed post. The graphic visual delineation of the memory of pain and hurt of such abuse which those women are forced to live with, subtly connect them to their fellow survivors in a manner that words cannot attain.

Predicting Survival for Chimeric Antigen Receptor T-Cell Therapy: A Validation of Survival Models Using Follow-Up Data From ZUMA-1

ObjectivesSurvival extrapolation for chimeric antigen receptor T-cell therapies is challenging, owing to their unique mechanistic properties that translate to complex hazard functions. Axicabtagene ciloleucel is indicated for the treatment of relapse or refractory diffuse large B-cell lymphoma after 2 or more lines of therapy based on the ZUMA-1 trial. Four data snapshots are available, with minimum follow-up of 12, 24, 36, and 48 months. This analysis explores how survival extrapolations for axicabtagene ciloleucel using ZUMA-1 data can be validated and compared. MethodsThree different parametric modeling approaches were applied: standard parametric, spline-based, and cure-based models. Models were compared using a range of metrics, across the 4 data snapshot, including visual fit, plausibility of long-term estimates, statistical goodness of fit, inspection of hazard plots, point-estimate accuracy, and conditional survival estimates. ResultsStandard and spline-based parametric extrapolations were generally incapable of fitting the ZUMA-1 data well. Cure-based models provided the best fit based on the earliest data snapshot, with extrapolations remaining consistent as data matured. At 48 months, the maximum survival overestimate was 8.3% (Gompertz mixture-cure model) versus the maximum underestimate of 33.5% (Weibull standard parametric model). ConclusionsWhere a plateau in the survival curve is clinically plausible, cure-based models may be helpful in making accurate predictions based on immature data. The ability to reliably extrapolate from maturing data may reduce delays in patient access to potentially lifesaving treatments. Additional research is required to understand how models compare in broader contexts, including different treatments and therapeutic areas.

2020 Pennsylvania Patient Safety Reporting: Updated Acute Care Reporting Rates

In our recent article summarizing 2020 data from acute care facilities in Pennsylvania, reporting rates and fall rates were provided for Q1 and Q2 2020 based on the latest data we had available at the time of publication. Given that 2020 was an unpredictable year in healthcare, any forecasting of rates for Q3 and Q4 2020 would have been unreliable. Therefore, this data snapshot serves to complete reporting rates for 2020 now that all hospital patient days and surgical encounters data from 2020 have been made available for rate calculations.

Low rate of worsening renal function after 2 years of treatment with edoxaban in patients from the ETNA-AF-Europe study

Abstract Background Use of vitamin K antagonists (VKAs) is associated with a crude event rate of 23% per year for worsening renal function (WRF). Although non-vitamin K antagonist oral anticoagulants (NOACs) have been associated with a lower risk of longitudinal decline in renal function compared with VKAs, available evidence on renal function decline in patients using NOACs is still limited. Furthermore, renal function is a dose reduction criterion for NOACs, which poses an important question about how physicians should treat patients whose renal function worsens over time. Purpose To evaluate the degree of renal function decline in AF patients treated with edoxaban after 2 years of follow-up, and to investigate clinical outcomes of patients with vs without WRF in the ETNA-AF-Europe study. Methods ETNA-AF-Europe is a multinational, multicentre, observational, post-authorisation safety study conducted in 825 sites in 10 European countries. Results are based on a data snapshot taken on 26th October 2020 which include data up to 2 years of follow-up. Patients were excluded from the analysis population if data to calculate estimated glomerular filtration rate [eGFR] were not available for at least one of the follow-up time-points of 1-year and 2-year. We categorised patients (n=9084) into two subgroups: 1) those with WRF (i.e. ≥25% decline in eGFR from baseline; n=918), and 2) those without WRF (n=8166). eGFR was estimated using the Cockcroft-Gault formula. Baseline characteristics and annualised event rates including 95% confidence intervals were analysed using descriptive analyses. Results Of the 13,417 patients in ETNA-AF-Europe who were included in the 2-year follow-up analysis, 9084 were included in this subgroup analysis, of whom 56.2% were male. Baseline eGFR were similar between patients with and without WRF when comparing across the different renal function categories (Table 1). The majority of the edoxaban-treated patients did not experience WRF (89.9%) during the 2 years of follow-up. The proportion of patients with WRF (10.1%) were older, more often frail and had higher rates of underlying comorbidities, such as diabetes, hypertension and heart failure (Table 1). Patients with WRF had higher annualised event rates of all-cause and cardiovascular death than those without (3.78% vs 1.90% and 2.06% vs 0.92%, respectively). Major bleeding and stroke rates were low, but numerically higher in patients with renal worsening compared to those without WRF (Figure 1). Intracranial haemorrhage rates remained low (0.17% vs 0.19%; Figure 1) in both subgroups. Conclusions This subgroup analysis provides real-world evidence for a low risk of WRF in AF patients treated with edoxaban over a 2-year period. Patients with WRF had higher mortality than those without, as well as numerically higher major bleeding and stroke rates. Importantly, intracranial haemorrhage rates remained low irrespective of WRF. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Europe GmbH /

Impact of Hypofractionated Radiotherapy on Patient-reported Outcomes in Prostate Cancer: Results up to 5 yr in the CHHiP trial (CRUK/06/016)

BackgroundModerate hypofractionation is the recommended standard of care for localised prostate cancer following the results of trials including Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy in Prostate Cancer (CHHiP). Evaluation of long-term patient-reported outcomes (PROs) is important to confirm safety and enhance patient information. ObjectiveTo determine whether 5-yr PROs from the CHHiP quality of life (QoL) substudy confirm 2-yr findings and assess patterns over follow-up. Design, setting, and participantsA phase III randomised controlled trial recruited from 2002 to 2011. The QoL substudy completed accrual in 2009; participants were followed up to 5 yr after radiotherapy. Analyses used data snapshot taken on August 26, 2016. A total of 71 radiotherapy centres were included in the study (UK, Republic of Ireland, Switzerland, and New Zealand); all 57 UK centres participated in the QoL substudy. CHHiP recruited 3216 men with localised prostate cancer (cT1b-T3aN0M0). InterventionConventional (74 Gy/37 fractions/7.4 wk) or hypofractionated radiotherapy (60 Gy/20 fractions/4 wk or 57 Gy/19 fractions/3.8 wk) was delivered with intensity-modulated techniques. Outcome measurements and statistical analysisUniversity of California Los Angeles Prostate Cancer Index, Short Form 36 and Functional Assessment of Cancer Therapy—Prostate, or Expanded Prostate Cancer Index Composite and Short Form 12 questionnaires were administered at baseline, before radiotherapy, at 10 wk, and at 6, 12, 18, 24, 36, 48, and 60 mo after radiotherapy. The QoL primary endpoint was overall bowel bother. Results and limitationsThe QoL substudy recruited 2100 patients; 1141 5-yr forms were available from 1957 patients still alive (58%). There were no statistically significant differences in 5-yr prevalence of overall “moderate or big” bowel bother: 19/349 (5.4%), 29/381 (7.6%), and 21/393 (5.3%) for 74, 60, and 57 Gy, respectively; overall urinary or sexual bother at 5 yr was similar between schedules. Bowel and urinary symptoms remained stable from 2 to 5 yr for all schedules. Some evidence of worsening overall sexual bother from baseline to 5 yr was less likely in the hypofractionated schedules compared with 74 Gy (odds ratios for increase in bother score vs 74 Gy: 0.55 [0.30–0.99], p = 0.009 for 60 Gy, and 0.52 [0.29–0.94], p = 0.004 for 57 Gy). General QoL scores were similar between schedules at 5 yr. ConclusionsLonger follow-up confirms earlier findings, with similar patient-reported bowel, urinary, and sexual problems between schedules overall. The continued low incidence of moderate or high bother confirms that moderate hypofractionation should be the standard of care for intermediate-risk localised prostate cancer. Patient summaryWe looked at patient-reported outcomes up to 5 yr after treatment in a trial of different radiotherapy schedules for prostate cancer. The findings confirmed that shorter radiotherapy schedules were as safe as standard radiotherapy in terms of bowel, urinary, and sexual problems. Take Home MessageBowel, urinary, and sexual symptoms were similar between schedules up to 5 yr. The continued low incidence of moderate/high bother confirms that moderate hypofractionated radiotherapy should be considered the standard of care for men with intermediate-risk prostate cancer.

A 26-Year Study of Restraint Fatalities Among Children and Adolescents in the United States: A Failure of Organizational Structures and Processes

BackgroundPhysical and mechanical restraints used in treatment, care, education, and corrections programs for children are high-risk interventions primarily due to their adverse physical, emotional, and fatal consequences.ObjectiveThis study explores the conditions and circumstances of restraint-related fatalities in the United States by asking (1) Who are the children that died due to physical restraint? and (2) How did they die?MethodThe study employs internet search systems to discover and compile information about restraint-related fatalities of children and youth up to 18 years of age from reputable journalism sources, advocacy groups, activists, and governmental and non-governmental agencies. The child cohort from a published study of restraint fatalities in the United States from 1993 to 2003 is combined with restraint fatalities from 2004 to 2018. This study’s scope has expanded to include restraint deaths in community schools, as well as undiscovered restraint deaths from 1993 to 2003 not in the 2006 study.ResultsSeventy-nine restraint-related fatalities occurred over the 26-year period from across a spectrum of children’s out-of-home child welfare, corrections, mental health and disability services. The research provides a data snapshot and examples of how fatalities unfold and their consequences for staff and agencies. Practice recommendations are offered to increase safety and transparency.ConclusionsThe study postulates that restraint fatalities result from a confluence of medical, psychological, and organizational causes; such as cultures prioritizing control, ignoring risk, using dangerous techniques, as well as agencies that lack structures, processes, procedures, and resources to promote learning and to ensure physical and psychological safety.

Single-Snapshot Angle and Incremental Range Estimation for FDA-MIMO Radar

This article deals with the problem of angle and incremental range (i.e., the target range offset with respect to the center of the cell under test) estimation with a frequency diverse array multiple-input multiple-output (FDA-MIMO) radar exploiting a single data snapshot as observable. Starting from the observation that the maximum likelihood (ML) estimation entails a 2-D grid search over the parameters of interest, three approximated ML techniques are designed resorting to the coordinate descent algorithm and the adaptive monopulse criterion (employing either real or complex slope/bias corrections). At the analysis stage, the estimation performance of the proposed methods, including the tapered and double-step monopulse versions, is also assessed in comparison with the Cramér–Rao lower bound. Numerical results corroborate the effectiveness of the considered estimation strategies in some diverse simulated scenarios.

Data Snapshot: Nasogastric Tube Misplacements

Nasogastric and orogastric tubes, herein collectively referred to as nasogastric tubes (NGT), are inserted into a patient’s nasal or oral cavity to administer feedings or medications or remove stomach contents. Tube misplacement is a known complication that can occur during insertion. This NGT misplacement data snapshot provides updated information.

Mantis shrimp-inspired organic photodetector for simultaneous hyperspectral and polarimetric imaging.

Combining hyperspectral and polarimetric imaging provides a powerful sensing modality with broad applications from astronomy to biology. Existing methods rely on temporal data acquisition or snapshot imaging of spatially separated detectors. These approaches incur fundamental artifacts that degrade imaging performance. To overcome these limitations, we present a stomatopod-inspired sensor capable of snapshot hyperspectral and polarization sensing in a single pixel. The design consists of stacking polarization-sensitive organic photovoltaics (P-OPVs) and polymer retarders. Multiple spectral and polarization channels are obtained by exploiting the P-OPVs' anisotropic response and the retarders' dispersion. We show that the design can sense 15 spectral channels over a 350-nanometer bandwidth. A detector is also experimentally demonstrated, which simultaneously registers four spectral channels and three polarization channels. The sensor showcases the myriad degrees of freedom offered by organic semiconductors that are not available in inorganics and heralds a fundamentally unexplored route for simultaneous spectral and polarimetric imaging.