Interim Findings Research Articles

Extending the Life Cycle of EEE—Findings from a Repair Study in Germany: Repair Challenges and Recommendations for Action

The increasing amount of waste from electrical and electronic equipment and the resulting environmental issues are challenging, since product life cycles are too short, and companies continue to rely on linear (business) models. The Circular Economy is an approach to meet these challenges by extending the product lifetime. One way to extend the product lifetime is to repair them. However, since there has been no detailed research on the repair sector yet, this article aims at conducting a repair study in Germany to understand the repair process and get insights into typical failure patterns. Therefore, we analyze the repair sector’s current barriers from different perspectives, especially of customers and businesses. We discuss the results of the repair study, where 382 repair attempts were conducted, with a total success rate of 55%. Moreover, the participants were interviewed to understand their barriers and motivation for repair. Based on the study’s interim findings, recommendations for action are given to make the repair services more attractive for the repairer and customer. Based on the findings, an interdisciplinary approach to improve repair processes by using a digital repair portal is derived.

Impact of lanadelumab on patient-reported outcomes in hereditary angioedema in the US and Canada: Interim findings from the EMPOWER Study

Efficacy and safety of lanadelumab in patients with HAE-C1-INH were evaluated in phase 3 clinical trials (NCT02586805; NCT02741596). An objective of EMPOWER, an ongoing observational, real-world study, is to describe lanadelumab users’ patient-reported outcomes (PROs) over time.

Safety and immunogenicity of an AS03-adjuvanted SARS-CoV-2 recombinant protein vaccine (CoV2 preS dTM) in healthy adults: interim findings from a phase 2, randomised, dose-finding, multicentre study

Safety and immunogenicity of an AS03-adjuvanted SARS-CoV-2 recombinant protein vaccine (CoV2 preS dTM) in healthy adults: interim findings from a phase 2, randomised, dose-finding, multicentre study

US college women’s understandings of definitions of intimate partner violence

Objective: Past research suggests students have differing definitions of sexual assault, violence and intimate partner violence (IPV). To adequately develop violence prevention efforts, it is important to examine how college students understand these terms and associated behaviours. The purpose of this study was to identify which behaviours are categorised as IPV by college women and whether there are any ‘grey areas’ when it comes to IPV. Design: A three-phase e-Delphi study was conducted with US college women to reach consensus on the behaviours commonly associated with IPV. Setting: The study was conducted in one large, Southeastern USA university. Method: In a first phase of work, participants answered open-ended questions about the behaviours they associated with IPV and related terms. In phase 2, participants categorised the behaviours identified in phase 1. In phase 3, consensus was reached by the 12 women who completed all three phases of work. Results: Women agreed on a list of 45 behaviours that constitute IPV as well as behaviours that fall into a ‘grey area’, with many of the latter occurring between boyfriends/girlfriends. Conclusion: Findings from the study contribute to the current knowledge base concerning IPV among US college students and their understanding of which behaviours are acceptable by intimate partners and which are not. Future research is needed with a larger more representative sample to extend the current findings. However, interim findings can be used to drive future research and may provide some insight into current student perceptions of IPV.

Negative Anthropology

Is there an architectural and urban planning agenda at work behind the politics of contemporary (neo-)fascists and populist, radical and extremist right-wing forces? The Right-Wing Spaces research project, which has been running since 2018 at the Institute for Principles of Modern Architecture (Design and Theory) (IGmA) at the University of Stuttgart, suggests that the answer to this question is fairly unequivocal, at least in the German context: ‘architecture … seems to have become a key tool of an authoritarian, populist right with a revisionist take on history.’[i] The interim findings of the project were presented in ‘Rechte Räume: Bericht einer Europareise’ (Right-wing spaces: report on a journey through Europe), ARCH+ 235 (2019), an issue that was guest-curated by IGmA, as well as in my 2020 essay collection Rechte Räume: Politische Essays und Gespräche (Right-wing spaces: political essays and conversations). [i] Stephan Trüby, Rechte Räume: Politische Essays und Gespräche (Basel: Birkhäuser, 2020), 138. The Right-Wing Spaces research project is headed by Philipp Krüpe (IGmA) and myself, https://www.igma.uni-stuttgart.de/en/research/research-projects/page_0002_0001/.

Results of an Interim Analysis of a Prospective Multicenter Study Assessing Radiographic and Patient Outcomes Following Triplanar Tarsometatarsal Arthrodesis with Early Weightbearing

Category:Bunion; Midfoot/ForefootIntroduction/Purpose:The majority of hallux valgus corrections are performed via a two dimensional approach with 1st metatarsal osteotomy and translation in the transverse plane. This approach has demonstrated high long-term recurrence rates. Recent research demonstrates that 87% of hallux valgus deformities are three-dimensional with abnormal frontal-plane rotation of the metatarsal, which cannot be completely addressed with a two dimensional metatarsal osteotomy alone. While correction at the 1st tarsometatarsal (TMT) joint may provide the optimal surgical approach for 3D anatomic restoration at the apex of the deformity, 1st TMT fusion entails an extended period of non-weightbearing. This study evaluated the clinical, radiographic, and patient-reported outcomes in patients undergoing instrumented triplanar 1st TMT arthrodesis (TMTA) with a biplanar plating system and protected near-immediate weightbearing.Methods:This is a prospective multicenter study that will continue for 60 months post-operatively. Patients between 14-58 years old with symptomatic hallux valgus (intermetatarsal and hallux valgus angles between 10.0-22.0° and 16.0-40.0°, respectively) and no prior hallux valgus surgery on the operative foot are eligible for this study. Patients are treated with an instrumented TMTA procedure using a biplanar plating system with protected near-immediate weightbearing. Several outcomes (radiographic, range of motion (ROM), return to weightbearing and activities, pain measured by visual analog scale (VAS), Manchester-Oxford Foot Questionnaire (MOxFQ), and Patient Reported Outcomes Measurement Information System (PROMIS)) are evaluated post- operatively. Two independent fellowship trained musculoskeletal radiologists reviewed all radiographic data. These interim results are limited to patients completing at least 6 months of follow-up.Results:At time of analysis, 121 patients had undergone TMTA with at least 6 months of follow-up. Mean age was 40.6 (range:15- 58) years, and 91% of patients were female. Mean (SD) days to protected weightbearing in CAM boot, return to work, and return to full work were 8.2 (6.8), 24.0 (29.5), and 51.2 (44.0), respectively. Significant improvements (p<0.05) from baseline in HVA, IMA, and TSP (Table 1), VAS score, MOxFQ and PROMIS domains were observed as early as 6 weeks post-procedure. At 12 months, mean (95% CI) change in VAS score was -4.0 (-4.5, -3.6); Walking/Standing, Pain, and Social Interaction (MOxFQ domains) change was -38.6 (-43.6, -33.5), -41.0 (-45.8, -36.2), and -40.5 (-45.3, -35.7), respectively; and physical function (PROMIS) change was 8.7 (6.6, 10.8).Conclusion:These interim findings support that TMTA with biplanar plating is successful in correcting the 3D hallux valgus deformity with early return to weightbearing while demonstrating favorable clinical and patient-reported outcomes. Patients exhibited meaningful pain reduction after surgery and were able to return to full, unrestricted work and activities in less than two months, on average. Statistically significant improvements in patients' health-related quality of life were observed at 6 and 12 months, post-operatively. Patients will continue to be followed for up to 60 months with additional evaluations for complications, 24-month recurrence, and patient satisfaction.

Phase 1/2 Clinical Trial of COVID-19 Vaccine in Japanese Participants: A Report of Interim Findings

Phase 1/2 Clinical Trial of COVID-19 Vaccine in Japanese Participants: A Report of Interim Findings

73. Interim Resistance Analysis of Long-Acting Lenacapavir in Treatment-Naïve People with HIV at 28 Weeks

BackgroundLenacapavir (LEN) is a first-in-class HIV-1 capsid (CA) inhibitor in clinical development for treatment and prevention of HIV-1 infection. CALIBRATE is an ongoing, phase 2 clinical study evaluating subcutaneous (SC) or oral LEN, in combination with other antiretrovirals, in treatment-naïve people with HIV-1. High rates of virologic success (HIV-1 RNA < 50 copies/mL) were achieved with LEN-based regimens by FDA Snapshot analysis at Week 28. Here, we present interim resistance analyses through Week 28. MethodsParticipants were randomized (2:2:2:1) to treatment groups (TG) (Figure): SC LEN + oral daily emtricitabine/tenofovir alafenamide (F/TAF); at Week 28, participants switch F/TAF to oral TAF (TG-A) or bictegravir (B, BIC) (TG-B); oral daily LEN + F/TAF (TG-C), or oral daily B/F/TAF (TG-D). Genotypic analyses (population sequencing) of HIV-1 reverse transcriptase and integrase, and genotypic (deep sequencing)/phenotypic analyses for CA were performed at screening; genotypic and phenotypic analyses were conducted at confirmed virologic failure. FigureCALIBRATE Study Design Results182 participants were randomized and dosed in TG-A to D (n=52, 53, 52, 25). Most participants had subtype B HIV-1 (92.9%). Sequence analysis of baseline samples found 65% of amino acid residues were conserved with < 1% variation across CA overall, and 55% of residues were fully conserved. No mutations were detected at 6 positions in CA associated with reduced susceptibility to LEN in vitro; residues were fully conserved at 5 positions (L56, M66, Q67, K70, N74), and < 2% variation was observed at 1 position (T107). Three participants met the criteria for resistance analysis: 2 participants resuppressed to < 50 copies/mL while continuing treatment. One participant on SC LEN + F/TAF developed emergent resistance to LEN (Q67H+K70R) and emtricitabine (M184M/I), followed by resuppression after starting dolutegravir, zidovudine + lamivudine, tenofovir disoproxil fumarate. ConclusionEmergent resistance to LEN was uncommon in treatment-naïve participants receiving SC or oral LEN (0.6%, 1/157). These interim resistance findings support the ongoing evaluation of LEN for treatment and prevention of HIV.Disclosures Laurie VanderVeen, PhD, Gilead Sciences (Employee, Shareholder) Nicolas Margot, MA, Gilead Sciences (Employee, Shareholder) Vidula Naik, MSc, Gilead Sciences (Employee, Shareholder) Silvia Chang, Masters, Gilead Sciences, Inc (Employee, Shareholder) Ross Martin, PhD, Gilead Sciences, Inc (Employee, Shareholder) Hadas Dvory-Sobol, PhD, Gilead Sciences (Employee, Shareholder) Martin Rhee, MD, Gilead Sciences (Employee, Shareholder) Christian Callebaut, PhD, Gilead Sciences (Employee, Shareholder)

CTIM-27. LOCOREGIONAL B7-H3-SPECIFIC CAR T CELLS FOR CHILDREN AND YOUNG ADULTS WITH DIPG: INTERIM REPORT OF BRAINCHILD-03 ARM C

Abstract Following preclinical optimization of B7-H3-specific CAR T cells against pediatric brain tumor models, we opened BrainChild-03 (NCT04185038), a phase 1 clinical trial of repeatedly dosed, outpatient, locoregional B7-H3-specific CAR T cells for children with recurrent/refractory central nervous system (CNS) tumors or diffuse intrinsic pontine glioma (DIPG). Here, we report the interim findings from patients enrolled on Arm C, dedicated to DIPG. The primary endpoints are feasibility and safety, with secondary endpoints of disease response. We utilize second-generation CAR T cells with a 4-1BB costimulatory domain and a methotrexate-resistant human DHFR mutein (huDHFRFS; L22F,F31S), allowing for methotrexate selection. We do not deliver conditioning chemotherapy. The first three evaluable patients with DIPG all met feasibility for generating a balanced CD4:CD8 CAR T cell product, with 3.85x109 CAR T cells generated for S005, 4.29x109 for S008, and 2.45x109 for S012, allowing for greater than 6 months of biweekly dosing for each patient. All subjects were treated at Dose Level 1 (1x107 CAR T cells). S005 received 10 doses before clinical progression greater than 2 years from diagnosis, S008 has received 10 doses and continues on therapy with decreased tumor volume, and S012 has received 5 doses and continues on study with stable disease. There have been no dose limiting toxicities (DLT). 3/3 patients exhibited post infusion fever, headache, and elevated serum CRP but no evidence of cytokine release syndrome (CRS) or systemic CAR T cells. 0/3 patients required PICU admissions. In the cerebrospinal fluid (CSF), 2/3 patients have had elevations of cytokines such as CXCL10 and CCL2, as well as circulating CSF CAR T cells. Advanced serial patient CSF proteomic and transcriptomic profiling are underway. Ultimately, this report provides preliminary evidence that outpatient locoregional B7-H3 CAR T cells for children with DIPG may be feasible and tolerable.

Peripheral microcirculatory alterations are associated with the severity of acute respiratory distress syndrome in COVID-19 patients admitted to intermediate respiratory and intensive care units

BackgroundCOVID-19 is primarily a respiratory disease; however, there is also evidence that it causes endothelial damage in the microvasculature of several organs. The aim of the present study is to characterize in vivo the microvascular reactivity in peripheral skeletal muscle of severe COVID-19 patients.MethodsThis is a prospective observational study carried out in Spain, Mexico and Brazil. Healthy subjects and severe COVID-19 patients admitted to the intermediate respiratory (IRCU) and intensive care units (ICU) due to hypoxemia were studied. Local tissue/blood oxygen saturation (StO2) and local hemoglobin concentration (THC) were non-invasively measured on the forearm by near-infrared spectroscopy (NIRS). A vascular occlusion test (VOT), a three-minute induced ischemia, was performed in order to obtain dynamic StO2 parameters: deoxygenation rate (DeO2), reoxygenation rate (ReO2), and hyperemic response (HAUC). In COVID-19 patients, the severity of ARDS was evaluated by the ratio between peripheral arterial oxygen saturation (SpO2) and the fraction of inspired oxygen (FiO2) (SF ratio).ResultsHealthy controls (32) and COVID-19 patients (73) were studied. Baseline StO2 and THC did not differ between the two groups. Dynamic VOT-derived parameters were significantly impaired in COVID-19 patients showing lower metabolic rate (DeO2) and diminished endothelial reactivity. At enrollment, most COVID-19 patients were receiving invasive mechanical ventilation (MV) (53%) or high-flow nasal cannula support (32%). Patients on MV were also receiving sedative agents (100%) and vasopressors (29%). Baseline StO2 and DeO2 negatively correlated with SF ratio, while ReO2 showed a positive correlation with SF ratio. There were significant differences in baseline StO2 and ReO2 among the different ARDS groups according to SF ratio, but not among different respiratory support therapies.ConclusionPatients with severe COVID-19 show systemic microcirculatory alterations suggestive of endothelial dysfunction, and these alterations are associated with the severity of ARDS. Further evaluation is needed to determine whether these observations have prognostic implications. These results represent interim findings of the ongoing HEMOCOVID-19 trial.Trial registration ClinicalTrials.gov NCT04689477. Retrospectively registered 30 December 2020.

Some pupils should know better (because there is better knowledge than opinion). Interim findings from an empirical study of pupils\u2019 and teachers\u2019 understandings of knowledge and big questions in Religious Education

In this paper, we draw on interim findings of our research project on Religious Education (RE), knowledge and big questions. We have found Miranda Fricker’s concept of epistemic injustice useful in our analysis—that is, the notion that a person can be wronged “specifically in their capacity as a knower (Fricker 2007, 1). In interviews with Key Stage 3 pupils (aged 12–14) we found that for many pupils, their capacity to know was hindered by the prioritisation of respect for opinion. Where opinion is considered something not to be questioned, this seems to be a key indicator of epistemic disadvantage while some pupils valued and could employ criticality when considering knowledge claims (including opinions). Epistemic advantage in this way exacerbates epistemic injustice, broadening a gap between the epistemic haves and have-nots. This research is part of a larger project where we attempt to answer the question: ‘Does Religious Education have a distinctive contribution to make to the development of epistemic literacy?’. We begin with our account of epistemic literacy underpinned by Young’s powerful knowledge (Young and Muller 2010) and contextualise our data with discourses about knowledge and school education. We focus largely on the emergent theme of (respect for) opinions and we argue that the prioritisation of respect in RE is (for some pupils) a barrier to knowledge. We go on to explore why this matters for individuals, society and RE.

Mindfulness Awareness Is Associated With a Lower Risk of Anxiety and Depressive Symptoms in Older Adults With Neurocognitive Disorders.

Background: Apart from depressive disorders, there are great interests in adopting mindfulness based interventions (MBIs) for other mental health conditions. Depression and anxiety are common in people with neurocognitive disorders (NCD). The potential of MBIs as an adjuvant treatment in this cognitively at-risk group should be further explored.Objectives: The current study explored the association between depression and anxiety symptoms with dispositional mindfulness in older adults, and if same association stays in the context of cognitive impairment.Methods: The Hong Kong Mental Morbidity Survey for Older People (MMSOP) is an ongoing epidemiology study of the prevalence of neurocognitive and mental disorders in adults aged 60 years or over in Hong Kong. MMSOP evaluated cognitive function, psychiatric symptoms (Clinical Interview Schedule-revised, CIS-R), chronic physical disease burden, psychosocial support, and resilience factors, including dispositional mindfulness as measured by the Mindful Attention Awareness Scale (MAAS). We analyzed the impact of MAAS on CIS-R and potential moderation effects of mindfulness.Results: In March 2021, 1,218 community dwelling participants completed assessments. The mean age of the sample is 69.0 (SD 6.9) years. Eight hundred and two participants (65.7%) were not demented (CDR 0) and 391 (32%) and 25 (2%) were categorized as having mild NCD (CDR 0.5) and major NCD (CDR 1 or more), respectively. One hundred forty-three (11.7%) satisfied ICD-10 criteria for anxiety or depressive disorder as measured by CIS-R. Linear regression analysis showed that female gender, CIRS, and MAAS scores were significant factors associated with CIS-R scores. MAAS scores moderated and attenuated the impact CIRS on CIS-R (adjusted R2 = 0.447, p < 0.001). MAAS scores remained as significant moderator for CIRS in patients with NCD (CDR ≥ 0.5) (adjusted R2 = 0.33, p < 0.001).Conclusion: Interim findings of the MMSOP suggested that dispositional mindfulness is associated with lower level of mood symptoms in community dwelling older adults in Hong Kong. The interaction effects further suggested that high mindful awareness may reduce the adverse effects of chronic physical morbidity on mental health. The observation stayed in the participants with cognitive impairment. We should further explore MBIs as a non-pharmacological treatment for in older adults at-risk of physical morbidity and cognitive decline.

Accuracy of after-hours trauma cervical spine CT reporting by radiology trainees: Experiences from two Australian teaching hospitals.

Like many teaching hospitals in Australia, after-hours computed tomography (CT) reporting at our institution is undertaken by the on-call radiology registrar. The accuracy of these reports is important as management is often initiated based on the interim findings, prior to review by the consultant radiologist. A common exception to this approach is cervical CT (CCT), as many hospital protocols recommend patients to remain in spinal precautions until the report is finalised by a consultant, although there are very few studies to support this practice. The interim registrar reports for all CCTs performed after-hours over a 12-month period were retrospectively reviewed. The final consultant report was used as the gold standard to establish accuracy of the registrar report. The primary outcome was discrepancy between the provisional and final reports. Any discrepancy was classified as either an 'overcall' or 'miss'. Discrepancies were graded by the RADPEER scoring system. A total of 1084 after-hours CCT studies were reviewed. The number of cases positive for injury was 37 (3.4%). The total number of discrepancies was 14 (discrepancy rate 1.3%), including 4 overcalls (0.3%) and 10 misses (0.9%). The discrepancy rates for junior and senior registrars were 1.7% and 0.7% respectively. Only 5 misses (0.5%) were considered clinically significant. Registrars reporting after-hours CCT have low rates of discrepancy with very few clinically significant misses. However, the reduced registrar sensitivity for detection of cervical injury highlights the ongoing importance of consultant review in the process of cervical spine clearance pathways.

Luminal Clinical

Background and Aim: Upper gastrointestinal bleeding (UGIB) is a common gastrointestinal emergency and carries high morbidity and mortality. There are multiple risk factors for poorer outcomes, including malnutrition. Ascorbic acid is a water-soluble vitamin present in most plant foods. Dietary deficiency leads to scurvy, which may alter the natural history of UGIB through impaired tissue and mucosal integrity. Traditionally thought to be rare in developed countries, vitamin C deficiency (VCD) is now well described in patients with pneumonia, sepsis, and coronavirus disease 2019. There is a paucity of literature investigating the prevalence and clinical significance of VCD in patients with UGIB;interim findings reported by our group suggested a prevalence of >30%. The aim of this study was to establish the prevalence of VCD in patients presenting with UGIB and its association with clinical outcomes. Methods: We conducted a prospective cohort study of adult patients presenting with UGIB to two metropolitan tertiary hospitals in Melbourne, Australia, over a 12-month period (March 2020 to March 2021). Fasting vitamin C levels were obtained on admission. Patients were risk-stratified using the AIMS65 score, and baseline demographic data and outcomes were recorded. The primary outcome was the prevalence of VCD (serum vitamin C level < 23 μmol/L) and severe VCD (<12 μmol/L). Secondary outcomes included a composite endpoint of adverse events (AE), comprising inpatient death, intensive care unit (ICU) admission, rebleeding, surgery, angioembolization, or massive transfusion (≥4 units of red cells). Multivariate logistic regression was used to determine the association between vitamin C levels and the secondary endpoints. Subgroup analyses were performed in variceal and non-variceal UGIB and high-risk (AIMS65, ≥2) and low-risk (AIMS65, 0-2) UGIB. Results: A total of 227 patients were included. The median age was 65 years (IQR, 54-78), 145 (63.9%) were male, and the median AIMS65 score was 1 (IQR, 1-2). The etiology of UGIB was variceal bleeding in 20.3%, peptic ulcer disease in 44.1%, and other causes in 35.7%. The mean vitamin C level was 40 ± 26 μmol/L. In terms of patient outcomes, inpatient mortality was 4%, ICU admission occurred for 11.9%, and mean length of stay (LOS) was 7.7 ± 9.7 days. Red cell transfusion was required in 63.4% of patients, with a mean requirement of 2.2 ± 2.8 units. VCD was identified in 74 patients (32.6%), with severe deficiency in 32 (14.1%). VCD was associated with significantly higher in-hospital mortality (9.5% vs 1.3%, P = 0.01), prolonged LOS (10.8 vs 6.2 days, P < 0.01), rebleeding (17.6% vs 7.88%, P = 0.05), and a higher composite endpoint of AE (77% vs 54.9%, P < 0.01). On multivariate logistic regression, high-risk UGIB (odds ratio [OR], 3.24;95% CI, 1.42-7.42), VCD (OR, 2.28;95% CI, 1.11-4.71), and chronic liver disease (OR, 11.66;95% CI, 2.92-46.64) were all independently associated with the composite endpoint of AE. In subgroup analysis, VCD was associated with a significantly increased composite endpoint of AE in patients with non-variceal (74% vs 51%, P < 0.01) and low-risk (66% vs 44%, P = 0.04) UGIB. Conclusion: VCD is highly prevalent in patients with UGIB and associated with poorer outcomes, including higher mortality, rebleeding, and LOS. Interventional studies are required to determine the impact of early vitamin C supplementation on clinical outcomes.

The Target UK Study: Real-World Evidence of Molecular Response to Tyrosine Kinase Inhibitors Supports European Leukemianet 2013 Recommendations for the Management of Chronic Myeloid Leukaemia

Abstract Introduction: Several recent studies have shown the speed and depth of response to tyrosine kinase inhibitor (TKI) treatment to be an important indicator of patient outcomes in chronic myeloid leukaemia (CML) as reviewed in the most recent European evidence based recommendations for CML management (European LeukemiaNet [ELN] 2013; Baccarani et al, 2013). ELN2013 focuses on monitoring of molecular responses, describing “optimal”, “warning” and “failure” at specific milestones to guide changes in therapy. An early molecular response (EMR; BCR-ABL1 IS Methods: TARGET is an observational, retrospective study conducted at 14 UK secondary/tertiary care centres. Data on Pt's characteristics, TKI choice, and molecular responses were collected by review of medical records for adult Pts (≥18 years) with chronic phase CML. Pts first prescribed a TKI between January 2013 and October 2015 were eligible and were required to have at least 6 months follow-up. Data were analysed using descriptive statistics. Results: At data collection, median follow-up was 21.5 (range 6.0 to 40.5) months. Median age at first TKI was 53.7 (range 18.7 to 86.8) years and 52% Pts were male. Imatinib was used first line (1L) in 107 (85%) Pts, and a second generation (2G) TKI in 19 (15%) (nilotinib=18, dasatinib=1). During the observation period 52/126 (41%) Pts switched TKI at least once; 29/52 switched early (within 6 [+1] months) and 23/52 switched later. The documented main reason for first switch was resistance (for 36/52) while 16/52 Pts were switched for intolerance (n=13) or other reasons (n=3). The median time to switch was 5.5 (range 0.5 to 34.3) months for Pts switched due to intolerance and 6.7 (range 2.8-16.0) months for resistance. Molecular responses at ELN2013 milestones and rates of EMR, MMR and DMR achieved 1L and 2L during the observation period are shown in Table 1. In the 52 Pts who switched TKI during the observation period, an ELN 2013 “warning” or “failure” response was observed prior to switch in 19/52 and 21/52 Pts, respectively (note: 4/52 Pts had an “optimal” response and switched for intolerance; 8/52 had no evaluable test at ELN milestone). In the 74 Pts who remained on 1L TKI with no observed switch, 25/74 had a “warning” response and a further 6/74 had a “failure” response at one or more ELN2013 milestones. Rates of MMR and DMR (at any time) for Pts who switched TKI following a prior “warning” or “failure” response (40/52 Pts with median follow-up of 13.6 [range 0.3 to 35.4] months) were 48% (19/40) and 23% (9/40), respectively. In Pts with a “warning” or “failure” response who stayed on 1L TKI (31/74 with median follow-up of 18.0 months [range 6.0 to 37.9]), 29% (9/31) achieved a MMR and 10% (3/31) a DMR. Conclusions: Interim findings in this real-world UK cohort suggest that a higher proportion of Pts treated with 2G TKI (either 1L or 2L) achieve an EMR, MMR or DMR than Pts treated with imatinib. Early indications suggest that the probability of achieving an optimal response is greater in Pts who switch TKI following an ELN “warning” or “failure” response than those with suboptimal responses who remain on 1L therapy, and that an early switch to 2L TKI may be beneficial. The results also highlight that optimal responses can be achieved even in Pts with prior resistance to 1L. Overall, the results support the use of ELN2013 recommendations to guide TKI management. Further recruitment and extended follow-up are planned to enable more detailed analyses of UK real-world monitoring and management patterns against ELN2013 recommendations and molecular response. Download : Download high-res image (224KB) Download : Download full-size image Disclosures Milojkovic: ARIAD: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Incyte: Honoraria, Speakers Bureau. Clark: Novartis: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Ariad Pharmaceuticals: Honoraria. Byrne: Novartis: Consultancy, Speakers Bureau; Ariad Pharmaceuticals: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau. Raghavan: Novartis: Honoraria; Pfizer: Honoraria. Wandroo: Pfizer: Honoraria; BMS: Honoraria; Bayer: Honoraria. Ali: Novartis: Honoraria; BMS: Honoraria. Ryan: Novartis: Employment; Novartis: Employment. Friedrich: Novartis: Employment. Cross: Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau; Qiagen: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Ariad: Consultancy, Honoraria. Mead: Pfizer: Honoraria; Novartis: Honoraria, Research Funding, Speakers Bureau; BMS: Honoraria.

Nonacog Beta Pegol for Prophylactic Treatment of Children with Hemophilia B: Up to 3.5-Year Data from the Paradigm™5 Clinical Trial

Introduction: Nonacog beta pegol is a recombinant glycoPEGylated factor IX (FIX) with an extended half-life compared with conventional FIX products developed for the treatment of hemophilia B. Here, we review new interim findings from the ongoing extension of paradigm™5, a noncontrolled, phase 3 trial investigating the safety, efficacy, and pharmacokinetics of nonacog beta pegol for the prophylaxis and treatment of bleeds in previously treated pediatric patients.Methods: The main trial enrolled and treated 25 children (aged ≤12 years) with hemophilia B (FIX ≤2%). Patients were stratified into 2 age groups, younger (0-6 years) and older (7-12 years) children, and received nonacog beta pegol 40 IU/kg once weekly for 52 weeks. A total of 22 patients entered the subsequent extension phase: 11 younger and 11 older children. Here we present findings from a planned interim analysis, including all relevant exposures in the main and extension phases (cut-off date: April 1, 2016).Results: No patients developed inhibitors over a total in-trial exposure time of 71.03 years (mean [range] exposure: 2.84 years/patient [0.21-3.76 years]; total in-trial exposure days: 3811 [152.4/patient]). The mean nonacog beta pegol prophylaxis dose was 43.2 IU/kg and the mean annualized consumption was 2305.8 IU/kg/patient. Overall, 80 bleeds were reported in 20 patients, of which 37 occurred in 15 patients during the main phase (mean treatment period: 0.97 years/patient) and 43 bleeds occurred in 12 patients during the extension phase (2.13 years/patient). The overall estimated mean annualized bleeding rate (ABR; bleeds per patient per year) was 1.52 during the main phase and 0.92 during the extension phase. Overall, there were 25 spontaneous bleeds in 8 patients (estimated ABRspontaneous: 0.35), 51 traumatic bleeds in 18 patients (estimated ABRtraumatic: 0.72), and 35 joint bleeds in 15 patients (estimated ABRjoint: 0.49). The overall proportion of bleeds that showed a successful hemostatic response to treatment was 88.8% (91.7% and 87.5% in younger and older children, respectively) and 80.0% of bleeds resolved after 1 dose. In total, 459 treatment-emergent adverse events (AEs) were reported in 24 (96%) patients; the most common were cough (14 [56%] patients), contusion (10 [40%]), and pyrexia (10 [40%]). Only 8 AEs, occurring in 1 younger and 3 older children, were considered to be possibly/probably related to study medication; these were 2 occurrences of infusion/injection site pain and 1 each of abdominal pain, diarrhea, nausea, eosinophilia, headache, and wheezing. Four serious AEs (device-related infection, upper respiratory tract infection, food poisoning, and hemoptysis) occurred in 3 (12%) patients; none were considered to be related to study medication. No AEs led to study withdrawal. No systematic changes over time were seen for any hematologic, hepatic, or renal parameters. There were no indications of neurological adverse reactions and no developmental concerns in these young children who had been on-study for up to 3.5 years.Discussion/Conclusion: Up to 3.5-year data from the ongoing paradigm™5 extension trial confirm the longer-term safety and efficacy of nonacog beta pegol for the prevention and treatment of bleeds in children with hemophilia B. ABR generally decreased over time, with fewer bleeds throughout the extension phase of the trial compared with the main phase. Overall, N9-GP was well tolerated and no unexpected safety concerns were identified. DisclosuresKearney:Advisory board for Novo Nordisk, Bioverativ and Bayer: Speakers Bureau; Local PI research funding for Bayer, Bioverativ, Daiichi Sankyo, Grifols and Novo Nordisk: Research Funding. Santagostino:: Bayer, Shire, Pfizer, Novo Nordisk, Kedrion, Roche, Sobi, Bioverativ, CSL Behring, Grifols, Octapharma: Speakers Bureau; Bayer, Shire, Pfizer, Novo Nordisk, Kedrion, Roche, Sobi, Bioverativ: Other: Advisory board. Carcao:Baxalta (Shire), Biogen, CSL Behring, Novo Nordisk, Octapharma and Pfizer: Consultancy; Baxalta (Shire), Bayer, Biogen, CSL Behring, Novo Nordisk, Octapharma and Pfizer: Speakers Bureau; Baxalta (Shire), Bayer, Biogen, Novo Nordisk and Pfizer: Research Funding. Taki:CSL Behring: Research Funding; Baxalta, Bioverativ, Chugai, CSL Behring, Novo Nordisk and Octapharma: Other: Investigator in clinical trials ; Baxalta, Bayer, Bioverativ, Novo Nordisk and Pfizer: Speakers Bureau; Chugai and Bioverativ: Consultancy. Garly:Novo Nordisk A/S: Employment. Zak:Novo Nordisk A/S: Employment.

Interim findings from the Uni Connect Raising Higher Education Aspirations evaluation in Lincolnshire

This short article summarises the evaluation findings from the end of Year 1 Phase 2 Uni Connect Raising Higher Education Aspirations project in Lincolnshire. This national initiative, funded by the Office for Students, delivers targeted Higher Education outreach activities to young people in Years 9 to 13 in areas where the Higher Education participation of young people is much lower than expected based on GCSE-level attainment. These areas often coincide with where universities focus their widening participation efforts to help them meet their Access and Participation Plans. In Lincolnshire the project is managed and delivered by LiNCHigher, one of 29 local learning partnerships involved in the project nationally. The data were collected between March and July 2020 during the Covid-19 national lockdown when all schools were closed and draws primarily on data collected from six case study schools. Evaluation activity comprised an online student activity survey, semi-structured interviews with School and College Leads, LiNCHigher Area Engagement Officers and two student focus groups, conducted just prior to lockdown in early March. The evaluation found that, prior to Covid-19, interventions were beginning to have a positive impact on the Higher Education aspirations of all students and that schools both welcomed and valued the initiative highly. The evaluation report made several recommendations, including ensuring workshops are more interactive.

Applying SDGs as a systematic approach for incorporating sustainability in higher education

PurposeThe achievement of the sustainable development goals (SDGs) for all communities and jurisdictions require a comprehensive roadmap that encompasses all dimensions of data infrastructure, social, economic, environmental and governance ecosystems. With this in mind, this paper aims to establish the link between the curriculum and intended learning outcomes of undergraduate and postgraduate subjects offered by the University and sustainability. This study is a part of a wider university strategy to embed sustainability knowledge and values in the university curricula. The 17 SDGs developed as a part of the 2030 Agenda for Sustainability Development was used as tool to measure and map how the subjects are linked with sustainability.Design/methodology/approachTo incorporate sustainability into the curriculum, this paper developed an interdisciplinary approach for analysing the interconnection between the SDGs, the expected subject learning points and the relevant aspects of sustainability (geospatial information, the legal, policies and institutional components). As part of the approach, in the first phase of the study, qualitative data were collected through a review of published information on the SDGs and the content of the subjects available in the subject handbook. Subject codes were assigned to the keywords and key phrases extracted from the SDGs and the subject content, and then compared and matched to establish the link between the subjects and the SDGs. Six university schools offering over 2,157 subjects were investigated. In the second phase, a survey was conducted involving subject coordinators with the purpose of validating the findings of the first phase and determining the strength of the linkages between the subjects and the SDGs. In the third phase, a plugin was designed to be used in the digital twin platform developed in the UoM, allowing visualisation of the research outcomes.FindingsBased on the interim findings, it was found that some subjects within the schools are linked to more than one SDG. However, not all of the subjects within the schools can be linked to the SDGs. There is a scope of improvement for embedding sustainability in more subjects within the schools. Some of the schools were also found to have weak linkages with sustainability, which demonstrate the challenge in technical subjects in linking their subject contents with sustainability.Originality/valueThis study provides a methodology which enables the integration of sustainability into current state of the curricula at the university to be established. Further, with the advancement of geospatial technology and new visualisation opportunities through the use of the digital twin platform provides capabilities to communicate the outcomes of sustainability and involvement of each faculties and departments more effectively to the university community and wider stakeholders.

Vaccine Considerations for Multiple Sclerosis in the COVID-19 Era.

People with multiple sclerosis (MS) are at risk for infections that can result in amplification of baseline symptoms and possibly trigger clinical relapses. Vaccination can prevent infection through the activation of humoral and cellular immune responses. This is particularly pertinent in the era of emerging novel vaccines against severe acute respiratory syndrome coronavirus 2, the virus that causes coronavirus disease 2019 (COVID-19). MS disease-modifying therapies (DMTs), which affect the immune system, may impact immune responses to COVID-19 vaccines in people with MS. The objective of this article is to provide information on immune system responses to vaccinations and review previous studies of vaccine responses in people with MS to support the safety and importance of receiving currently available and emerging COVID-19 vaccines. Immunological studies have shown that coordinated interactions between T and B lymphocytes of the adaptive immune system are key to successful generation of immunological memory and production of neutralizing antibodies following recognition of vaccine antigens by innate immune cells. CD4+ T cells are essential to facilitate CD8+ T cell and B cell activation, while B cells drive and sustain T cell memory. Data suggest that some classes of DMT, including type 1 interferons and glatiramer acetate, may not significantly impair the response to vaccination. DMTs—such as sphingosine-1-phosphate receptor modulators, which sequester lymphocytes from circulation; alemtuzumab; and anti-CD20 therapies, which rely on depleting populations of immune cells—have been shown to attenuate responses to conventional vaccines. Currently, three COVID-19 vaccines have been granted emergency use authorization in the USA on the basis of promising interim findings of ongoing trials. Because analyses of these vaccines in people with MS are not available, decisions regarding COVID-19 vaccination and DMT choice should be informed by data and expert consensus, and personalized with considerations for disease burden, risk of infection, and other factors.

Fostamatinib: A Review in Chronic Immune Thrombocytopenia.

Fostamatinib (Tavalisse®; Tavlesse®) is the first spleen tyrosine kinase (Syk) inhibitor approved for the treatment of chronic immune thrombocytopenia (ITP) in adult patients who have had an insufficient response to previous treatment. By inhibiting Syk activation in macrophages, fostamatinib blocks autoantibody-mediated platelet phagocytosis. In the placebo-controlled phaseIII FIT1 and FIT2 trials, 24weeks of oral fostamatinib therapy increased platelet count in previously treated adults with ITP. A significantly higher proportion of patients achieved stable response with fostamatinib than with placebo in FIT1, but not in FIT2; however, pooled analyses of the two studies showed that fostamatinib produced significantly higher stable and overall response rates than placebo. Interim findings from the ongoing FIT3open-label extension study suggested that the efficacy of fostamatinib was maintained with long-term treatment (up to 62months; median duration 6months), including in patients receiving fostamatinib as second- or later-line treatment. Fostamatinib had a generally manageable tolerability profile in all three FIT studies, with no serious safety risks. Fostamatinib therefore provides an alternative treatment option for chronic ITP in adult patients with an insufficient response to previous treatment.