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1.
HemaSphere ; 6:1647-1648, 2022.
Article in English | EMBASE | ID: covidwho-2032170

ABSTRACT

Background: Lenalidomide (LEN) maintenance and continuous LEN-based induction therapy until disease progression have become standard of care for frontline therapy of multiple myeloma (MM). As such, an increasing number of patients (pts) in need of 2nd line therapy have LEN-refractory disease. Optimal treatment in this setting has not been rigorously assessed in randomized studies. The phase I portion of Alliance A061202 demonstrated the safety of the ixazomib-pomalidomide-dexamethasone (IXA-POM-DEX) combination for the treatment of pts with LEN and proteasome inhibitor (PI)-refractory MM. Aims: In the randomized phase II portion, we evaluated the addition of IXA to POM-DEX for PI naïve / sensitive pts progressing on LEN as part of 1st line therapy. The primary endpoint was progression-free survival (PFS). Key secondary endpoints included overall response rate (ORR), depth of response, survival and safety. Methods: Pts were randomized 1:1 to IXA-POM-DEX or POM-DEX and stratified by prior bortezomib exposure, International Staging System stage (1 and 2 vs 3) and the presence of high-risk cytogenetics. POM was administered at 4 mg on days 1-21;IXA 4 mg on days 1, 8 and 15;and DEX 20 mg (>75 years (yrs)) or 40 mg (≤75 yrs) on days 1, 8, 15 and 22 of a 28-day cycle. Treatment was continued until disease progression, the emergence of unacceptable side effects or withdrawal of treatment consent. Results: 38 and 39 eligible pts were assigned to IXA-POM-DEX and POM-DEX, respectively. The median age was 66 yrs (range 41-83) and 64 yrs (range 52-85). A planned first interim analysis was conducted after 43 out of 57 required events had occurred. PFS favored the IXA-POM-DEX arm (one-sided log rank test value = 4.6345, p=0.03134 [< p-value boundary of 0.058]), yielding a hazard ratio of 0.528 (upper 90% bound = 0.777). A stratified log-rank test found that PFS was superior for the triplet after adjusting for stratification factors (one-sided stratified log rank test value = 5.8371;p=0.0157), adjusted hazard ratio 0.451 (upper 90% bound = 0.694). The ORR favored IXA-POM-DEX (63.2% vs 43.6%, p=0.0853), and the ≥very good partial response was 26.3% vs 5.1%, respectively (p=0.01). The clinical benefit rate (ORR + minimal response rate) was 73.7% and 56.4%. The most common grade 3/4 adverse events included lymphopenia, neutropenia, anemia, and fatigue in 40%, 37%, 16% and 16% of IXAPOM-DEX-treated pts and 26%, 21%, 13%, and 15% of POM-DEX-treated pts. Therapy was discontinued for disease progression in 47.4% of pts on IXA-POM-DEX and 76.9% of pts on POM-DEX and for adverse events in 7.9% and 7.7% of pts, respectively. Summary/Conclusion: The addition of IXA to the POM-DEX backbone improved the depth of response and PFS for pts relapsing on LEN as part of 1st line therapy. Hematologic toxicity was increased with the addition of IXA, but side effects were manageable. The ease of administration of this all-oral combination allowed for safer, uninterrupted treatment during the COVID pandemic. Our results should be confirmed in phase III trials but lend support for this regimen as part of 2nd line therapy for this patient population.

2.
Neurology ; 98(18 SUPPL), 2022.
Article in English | EMBASE | ID: covidwho-1925478

ABSTRACT

Objective: NA Background: Creutzfeldt-Jakob disease (CJD) is an extremely rare but fatal neurodegenerative disease with incidence of one in a million worldwide, and few than 1000 cases per year in the United States per year. Design/Methods: NA Case Summary: We present two probable CJD cases seen in the same hospital within one month. Case one was a 67-year-old white female, former psychology practice manager, presenting with worsening cognition, vertigo, behavioral changes and 15 lb weight loss over 6 months. Exam findings significant for MoCA of 17/30 (decreased to 15/30 after one week), constant right eye shut, mild dysmetria in both lower extremities, a wide based gait with small strides. Blood work and initial Spinal fluid studies were negative. Continuous EEG showing occasional right temporal slow, frequent generalized rhythmic theta and delta slowing. MRI brain findings were suggestive of CJD with hyperintensities in bilateral caudate nucleus and putamen. Patient did not respond to high dose steroid. Case two was a 78-year-old white male, admitted for deterioration in cognition, gait, speech, fatigue and intermittent body jerking. Progression of his symptoms was so rapid, from a highly functional retired funeral director, he became minimal speech, loss of ADL within 3 months. Exam was significant for orientation to self only, global aphasia, muscle weakness and startle myoclonus. Blood work and initial spinal fluid studies were negative. MRI brain showed asymmetric cortically based diffuse restriction within cingulate, caudate nucleus also left temporoparietal. EEG showed generalized rhythmic delta activity. CSF from both cases eventually showed positive RT-QuIC, 14-3-3 protein and highly elevated T-Tau protein. Conclusions: CJD is a transmittable, reportable disease. Two cases seen in the same hospital within one month skews from the previously known CJD prevalence. Surveillance and investigation on the reason of regional CJD arise during COVID-19 pandemic may prove to be important and urgent.

3.
Embase; 2021.
Preprint in English | EMBASE | ID: ppcovidwho-335728

ABSTRACT

There is strong evidence for brain-related abnormalities in COVID-191-13. It remains unknown however whether the impact of SARS-CoV-2 infection can be detected in milder cases, and whether this can reveal possible mechanisms contributing to brain pathology. Here, we investigated brain changes in 785 UK Biobank participants (aged 51-81) imaged twice, including 401 cases who tested positive for infection with SARS-CoV-2 between their two scans, with 141 days on average separating their diagnosis and second scan, and 384 controls. The availability of pre-infection imaging data reduces the likelihood of pre-existing risk factors being misinterpreted as disease effects. We identified significant longitudinal effects when comparing the two groups, including: (i) greater reduction in grey matter thickness and tissue-contrast in the orbitofrontal cortex and parahippocampal gyrus, (ii) greater changes in markers of tissue damage in regions functionally-connected to the primary olfactory cortex, and (iii) greater reduction in global brain size. The infected participants also showed on average larger cognitive decline between the two timepoints. Importantly, these imaging and cognitive longitudinal effects were still seen after excluding the 15 cases who had been hospitalised. These mainly limbic brain imaging results may be the in vivo hallmarks of a degenerative spread of the disease via olfactory pathways, of neuroinflammatory events, or of the loss of sensory input due to anosmia. Whether this deleterious impact can be partially reversed, or whether these effects will persist in the long term, remains to be investigated with additional follow up.

4.
Journal of Chemical Education ; : 7, 2022.
Article in English | Web of Science | ID: covidwho-1621205

ABSTRACT

The COVID-19 pandemic redefined how chemistry laboratories were taught. It also introduced a racial health disparity for Black and Brown people. The General Chemistry I laboratory curriculum at a Historically Black College and University (HBCU) in Baltimore, MD, was redesigned to meet student needs during this challenging time. While surrounded by civil unrest and uncertainty, we wanted to reach our underrepresented students in a way that they felt seen and heard. "The Mystery of Mr. Johnson" series was designed to reinforce the role chemistry can serve in advancing equity in their community. This interconnected series of three experiments (Solutions, Titration, Spectroscopy) developed chemistry laboratory skills which were applied to diabetes, a COVID-19 comorbidity, and health disparity highly prevalent in Baltimore. "The Mystery of Mr. Johnson" series provided opportunities for students to gain exposure to the role of chemistry in addressing a health disparity that impacts their community. The culminating project was a public service announcement to communicate lifestyle changes and the prevalence of diabetes in the black community.

5.
Australasian Leisure Management ; 140:52-52, 2020.
Article in English | GIM | ID: covidwho-1543484

ABSTRACT

This article explains how PBM Safety has adapted to COVID 19. PBM Safety is a division of PBM Enterprises, which services event and venue clients as specialists in safety and emergency management, risk consultancy, online staff and contractor inductions, weather forecasting, auditing for gaps in compliance or occupational health and safety management systems.

6.
8.
Journal of Decision Systems ; 2021.
Article in English | Scopus | ID: covidwho-1205489

ABSTRACT

Digital Transformation has generated much research and curiosity recently, with the COVID-19 global pandemic accelerating its pace across all industry sectors. Current literature has not adequately provided a comprehensive understanding of Digital Transformation Leadership (DTL). The objective of this research is to explore the characteristics of DTL by undertaking a comprehensive review of Information Systems literature using a systematic procedure of identifying and coding 87 research papers, resulting in 600 coded excerpts, capturing the ‘who’ and ‘what’ of DTL. Our analysis identifies eight DTL characteristics, namely: digital strategist, digital culturalist, digital architect, customer centrist, organisational agilist, data advocate, business process optimiser and digital workplace landscaper. We discuss mapping the DTL characteristics to c-suite roles, presenting a taxonomy from the literature, of interest to both academics and practitioners. This research raises the awareness of the concept of DTL characteristics, especially amongst those in positions of leadership and decision making authority. © 2021 Informa UK Limited, trading as Taylor & Francis Group.

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