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1.
British Journal of Haematology ; 201(Supplement 1):89, 2023.
Article in English | EMBASE | ID: covidwho-20236584

ABSTRACT

The phase 3 MOMENTUM study (NCT04173494) of the ACVR1/JAK1/JAK2 inhibitor momelotinib (MMB) vs. danazol (DAN) in patients with myelofibrosis (MF) previously treated with a JAK inhibitor (JAKi) met the primary endpoint and all key secondary endpoints at week 24 (W24). We provide updated results from week 48 assessments. Eligible patients had primary or post-ET/ PV MF;DIPSS high, Int-2, or Int-1 risk;Total Symptom Score (TSS) >=10;haemoglobin (Hb) <10 g/dL;platelets >=25 x 109/L;prior JAKi for >=90 days (>=28 days if red blood cell [RBC] transfusions >=4 units in 8 weeks or grade 3/4 thrombocytopenia/anaemia/ hematoma);and palpable spleen >=5 cm. Randomisation was 2:1 to MMB 200 mg/day or DAN 600 mg/day for 24 weeks, followed by open-label (OL) MMB. Week 48 endpoints included durations of response (TSS, transfusion independence [TI], splenic) and overall and leukaemia-free survival (OS, LFS). As of 17 May 2022, 93/130 (72%) MMB -> MMB and 41/65 (63%) DAN -> MMB patients received OL MMB;mean MMB durations were 48 weeks and 24 weeks, respectively. Analyses for W24 responders showed the following: of TSS responders, 31/32 (97%) MMB -> MMB and 6/6 DAN -> MMB patients had TSS < baseline;of TI responders, 36/40 (90%) and 10/13 (77%) had no RBC transfusions or Hb <8 g/dL;and of spleen responders, all patients had splenic volume < baseline. In the OL phase, the most common grade >=3 treatment-emergent adverse events (TEAEs) were thrombocytopenia (MMB -> MMB, 9%;DAN -> MMB, 15%) and anaemia (MMB -> MMB, 9%;DAN -> MMB, 2%). Grade >=3 infections occurred in 19% of MMB -> MMB and 10% of DAN -> MMB patients, including grade >=3 (nonfatal) COVID-19. Peripheral neuropathy (PN) occurred in 2% of patients in each arm, and none discontinued MMB due to PN. TEAEs led to MMB discontinuation in 18% (MMB -> MMB) vs. 10% (DAN -> MMB). A trend towards improved OS up to W24 was previously observed with MMB vs. DAN (hazard ratio [HR], 0.506;p = 0.0719);after all patients crossed over to OL MMB, OS and LFS curves for both arms converged (HR, 0.945, 95% CI, 0.528-1.693;HR, 0.830, 95% CI, 0.473-1.4555). Sixty of 81 (74%) MMB -> MMB and 29 of 43 (67%) DAN -> MMB patients with baseline platelets <=150 x 109/L entered the OL phase. Efficacy and safety results in thrombocytopenic subgroups in the OL period were consistent with the intent-to- treat (ITT) population. OL MMB maintained symptom, TI, and spleen responses with continued good survival and safety in the ITT and low platelet populations. MMB may address an unmet need in anaemic patients with MF.

2.
1st ACIS International Symposium on Emotional Artificial Intelligence and Metaverse, EAIM 2022 ; 1067:169-181, 2023.
Article in English | Scopus | ID: covidwho-2148559

ABSTRACT

In the COVID-19 pandemic, vaccines have emerged as the most effective tool to protect people from COVID-19. However, there is a limited study of adverse events (AEs) for COVID-19 vaccines among people with type 2 diabetes. The purpose of this study is to report the common adverse events following the COVID-19 vaccines, mRNA-1273, BNT162b2, and JNJ-78436735 in diabetic patients. We collected data for common adverse events to the COVID-19 vaccines using Vaccine Adverse Event Reporting System (VAERS). To identify the people with and without diabetes, we used the Natural language processing algorithms. After a 1:3 propensity score matching, we used 6,829 people with type 2 diabetes and 20,487 healthy control groups. Multiple logistic regression analysis was performed to obtain the odds ratio for 25 common AEs in order of high frequency. The most common AEs were pain (17.9%), headache (16.6%), pyrexia (13.4%), chills (12.4%), fatigue (12.0%), dizziness (11.0%). In particular, AEs of the dysmenorrhea in women were rare (0.14%), but a 15-fold higher frequency was observed in patients with diabetes (0.45% versus 0.03%) than in those with controls. The risk of all common AEs following both mRNA vaccines was significantly lower (OR = 0.87, 95% CI = 0.77–0.97, P = 0.015) than that after one viral vector vaccine, as well as the risk among males (OR = 0.56, 95% CI = 0.53–0.59, P < 0.001) was lower than among females. In conclusion, the risk of common adverse events among people with type 2 diabetes was low after both mRNA vaccines and in males. These findings might have implications for safe vaccine use. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.

3.
Physics of Fluids ; 34(10), 2022.
Article in English | Web of Science | ID: covidwho-2096933

ABSTRACT

Aerosolized droplets are produced en masse in dental practices;these aerosols disperse in the surrounding space, posing a health threat if the patient is infected with a transmittable disease, particularly COVID-19. Here, a viscoelastic polyacrylic acid (PAA) solution was used to minimize liquid aerosolization and limit the travel distance of aerosols. The PAA concentration was varied to evaluate its effect on aerosolization and droplet size resulting from procedures using dental handpieces, which include tooth cutting, grinding, and polishing. In addition, a thermocouple was inserted at the center of the model tooth to measure its temperature during a handpiece operation. The temperature data suggest that the cooling performance of the PAA solution is comparable to that of pure water in operations in the occlusal and facial directions. The PAA solution droplets splattered on the patient's facial area during the handpiece operation are markedly larger than those of pure water, which is evidence of the settling of the PAA droplets, preventing further transmission. Accordingly, the travel distance of the aerosolized PAA droplets was limited by viscoelastic resistance to droplet detachment. This comparison of the aerosol suppression capability between water and PAA solutions confirms the benefit of using viscoelastic solutions for various dental operations. Published under an exclusive license by AIP Publishing.

4.
Composites Research ; 35(3):216-221, 2022.
Article in English | Web of Science | ID: covidwho-1979609

ABSTRACT

Recently, the worldwide demand for disposable masks has increased due to COVID-19 infections and severe air pollution. Personal masks should reduce breathe resistance while maintaining filtering performance. In this study, a solution blowing process is used to produce composite nanofiber filters to co-spin two polymers at once. The manufacture process of the various fiber diameter filter was designed, and the filtration performance and differential pressure of the prepared filter was investigated. Poly vinylidene fluoride-hexafluoropropylene (PVDF-HFP) and Polylactic acid (PLA) fibers were chosen to be entangled together in a layer with a diameter of 1.05 mu m and 0.33 mu m. Composite nanofilters showed up to 87% filtration efficiency and 32 Pa differential pressure.

5.
Blood ; 138:3573, 2021.
Article in English | EMBASE | ID: covidwho-1582367

ABSTRACT

Background: Cytokine release syndrome (CRS) is a potentially serious complication of T-cell engaging immunotherapy. Effective measures are needed to reduce the rate and severity. In a multicenter Phase I/II study (NCT02500407), the CD20xCD3 bispecific antibody mosunetuzumab (Mosun) showed durable complete responses (CR) and had manageable safety in patients (pts) with late-line R/R B-NHL (Schuster et al. ASH 2019). IV administration with Cycle (C) 1 step-up dosing was an effective strategy for mitigating CRS during C1 (Bartlett et al. ASCO 2019). Fixed-dose SC administration was also a viable strategy for CRS mitigation, owing to the slower rate of Mosun absorption compared with IV (Matasar et al. ASH 2020). A combination of both strategies could further improve the CRS profile. We present safety and efficacy data from the initial cohorts investigating SC Mosun administration with C1 step-up dosing in the Phase I/II study. Methods: All pts had R/R B-NHL with ≥1 prior line of systemic therapy and ECOG PS ≤1. SC Mosun was given in 21-day cycles using two step-up dosing schedules (C1 day [D]1/C1D8/C1D15 and D1 of subsequent cycles: 5/15/45mg or 5/45/45mg). Mosun was discontinued after C8 in pts who achieved a CR, while pts with a partial response or stable disease continued Mosun for a total of 17 cycles, unless progressive disease or unacceptable toxicity occurred. Primary objectives included evaluation of safety, tolerability, and pharmacokinetics (PK). Responses were evaluated by investigator-assessment of PET/CT scans using Cheson 2007 criteria. CRS is reported using ASTCT criteria (Lee et al. Biol Blood Marrow Transplant 2019). Results: As of June 21, 2021, 74 pts had been enrolled (5/15/45mg: 38 pts;5/45/45mg: 36 pts). Median age was 67.0 years (range: 41-88). The most common NHL subtypes were DLBCL (31 pts), FL (21), transformed (tr) FL (10), and MCL (3). 70.0% of pts had Ann Arbor stage III or IV disease. Median number of prior lines of therapy was 3 (range: 1-9). 79.5% of pts were refractory to prior anti-CD20 therapy and 82.4% were refractory to their last prior therapy. Median follow-up for safety was 2.5 months (range: 0.2-7.2). No dose-limiting toxicities were observed during dose-escalation. Common all-Grade (Gr) adverse events (AEs;≥10% of pts) were injection site reaction (52.7%;Gr 1: 47.3%;Gr 2: 5.4%), CRS (24.3%), fatigue (21.6%), headache (17.6%), rash (13.5%), and pyrexia (10.8%). CRS mostly occurred in C1 and was low Gr in all pts (Gr 1: 17.6%;Gr 2: 6.8%);no Gr ≥3 CRS occurred. Gr 2 CRS occurred with a similar frequency in the 5/15/45mg and 5/45/45mg cohorts (7.9% vs 5.6% of pts, respectively). In the 5/15/45mg cohort, the 3 Gr 2 CRS events occurred after each of the C1 doses, while in the 5/45/45mg cohort, the 2 Gr 2 CRS events occurred after the first 45mg dose. Median duration of CRS was 2 days (range: 1-6) and all events resolved without sequelae. Neutropenia occurred in 12.2% of pts (Gr 2: 2.7%;Gr 3: 6.8%;Gr 4: 2.7%). Febrile neutropenia occurred in only 1 pt (Gr 3). Serious infections occurred in 3 pts (2 pneumonia, both resolved;1 COVID-19, fatal outcome). No Mosun-related Gr 5 (fatal) AEs or Mosun-related AEs leading to Mosun discontinuation occurred. The PK profile of SC Mosun was consistent with that previously reported, with high bioavailability (>85%), a slow absorption rate, and a blunted C max. IL-6 and IFN-y kinetics in plasma were similar in both SC cohorts, with modest and delayed increases observed after the initial dose, contrasting with the more marked and rapid increases observed with IV dosing, and consistent with the low frequency and severity of CRS observed. At data cut-off, 38 pts were efficacy evaluable. Responses were observed in 19 pts across all histologies, including 8/10 (80%) pts with R/R FL and 6/17 (35.3%) pts with R/R DLBCL/trFL. Conclusions: SC Mosun administration with C1 step-up dosing has a favorable safety profile in pts with late-line and highly refractory B-NHL, enabling an outpatient treatment schedule without mandatory hospitalizations. Encouragingly, the 5/45/45mg schedule had a low rate of CRS that was similar to the 5/15/45mg schedule, allowing the target dose to be reached earlier. Early response data suggest that the efficacy of Mosun is not compromised by SC dosing. Compared with IV, SC Mosun is likely to improve convenience for pts and efficiency for healthcare providers. Updated efficacy data with longer follow up and depth of response will be presented. Disclosures: Bartlett: Affimed: Research Funding;Autolus: Research Funding;Bristol-Myers Squibb: Research Funding;Celgene: Research Funding;Forty Seven: Research Funding;Janssen: Research Funding;Kite Pharma: Research Funding;Merck: Research Funding;Millennium: Research Funding;Pharmacyclics: Research Funding;Genentech, Inc./F. Hoffmann-La Roche Ltd: Membership on an entity's Board of Directors or advisory committees, Research Funding;Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding;ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding;Washington University School of Medicine: Current Employment. Giri: Royal Adelaide Hospital: Current Employment. Budde: Genentech, Inc.: Consultancy;Merck, Inc: Research Funding;Amgen: Research Funding;AstraZeneca: Research Funding;Mustang Bio: Research Funding;Novartis: Consultancy;Gilead: Consultancy;Roche: Consultancy;Beigene: Consultancy. Schuster: Celgene: Consultancy, Honoraria, Research Funding;Nordic Nanovector: Consultancy;Novartis: Consultancy, Honoraria, Patents & Royalties, Research Funding;Abbvie: Consultancy, Research Funding;Acerta Pharma/AstraZeneca: Consultancy;Alimera Sciences: Consultancy;BeiGene: Consultancy;Juno Theraputics: Consultancy, Research Funding;Loxo Oncology: Consultancy;Tessa Theraputics: Consultancy;Genentech/Roche: Consultancy, Research Funding;Pharmaclyclics: Research Funding;Adaptive Biotechnologies: Research Funding;Merck: Research Funding;Incyte: Research Funding;TG Theraputics: Research Funding;DTRM: Research Funding. Assouline: Johnson&Johnson: Current equity holder in publicly-traded company;Gilead: Speakers Bureau;Amgen: Current equity holder in publicly-traded company, Research Funding;Novartis: Honoraria, Research Funding;Eli Lilly: Research Funding;Roche/Genentech: Research Funding;Jewish General Hospital, Montreal, Quebec: Current Employment;Takeda: Research Funding;BeiGene: Consultancy, Honoraria, Research Funding;F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding;AstraZeneca: Consultancy, Honoraria;AbbVie: Consultancy, Honoraria, Research Funding, Speakers Bureau;Janssen: Consultancy, Honoraria;Pfizer: Consultancy, Honoraria. Matasar: Merck Sharp & Dohme: Current holder of individual stocks in a privately-held company;Juno Therapeutics: Consultancy;Janssen: Honoraria, Research Funding;Daiichi Sankyo: Consultancy;Genentech, Inc.: Consultancy, Honoraria, Research Funding;Bayer: Consultancy, Honoraria, Research Funding;Merck: Consultancy;Teva: Consultancy;TG Therapeutics: Consultancy, Honoraria;F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding;Takeda: Consultancy, Honoraria;GlaxoSmithKline: Honoraria, Research Funding;Seattle Genetics: Consultancy, Honoraria, Research Funding;Memorial Sloan Kettering Cancer Center: Current Employment;IGM Biosciences: Research Funding;Pharmacyclics: Honoraria, Research Funding;Rocket Medical: Consultancy, Research Funding;ImmunoVaccine Technologies: Consultancy, Honoraria, Research Funding. Canales: Takeda: Consultancy, Honoraria, Speakers Bureau;Incyte: Consultancy;Sandoz: Honoraria, Speakers Bureau;iQone: Honoraria;Sanofi: Consultancy;Novartis: Consultancy, Honoraria;Karyopharm: Consultancy, Honoraria;Eusa Pharma: Consultancy, Honoraria;Celgene/Bristol-Myers Squibb: Consultancy, Honoraria;Gilead/Kite: Consultancy, Honoraria;F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Speakers Bureau;Janssen: Consultancy, Honoraria, Speakers Bureau. Fay: St Vincent's Hosptial, Sydney, ustralia: Current Employment. Cheah: BMS: Consultancy, Research Funding;Abbvie: Research Funding;Janssen: Consultancy, Honoraria;MSD: Consultancy, Honoraria;Gilead: Consultancy, Honoraria;Ascentage Pharma: Consultancy, Honoraria;AstraZeneca: Consultancy, Honoraria;Lilly: Consultancy, Honoraria;TG therapeutics: Consultancy, Honoraria;Beigene: Consultancy, Honoraria;Novartis: Consultancy, Honoraria;Roche: Consultancy, Honoraria, Other: travel, Research Funding. Marlton: BeiGene: Honoraria, Membership on an entity's Board of Directors or advisory committees;F. Hoffmann-La Roche Ltd: Membership on an entity's Board of Directors or advisory committees;Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees;Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees;AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees;Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees;Astellas: Honoraria, Membership on an entity's Board of Directors or advisory committees;AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees;Queensland Health: Current Employment;Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees. Wiebking: Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company;F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Yin: Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months. To: Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company. Li: Genentech, Inc.: Current Employment, Current holder of individual stocks in a privately-held company. Huang:F. Hoffmann-La Roche Ltd: Current Employment. Zhou: Fibrogen China: Ended employment in the past 24 months;Roche Pharma Product Development: Current Employment. Penuel: Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company. O'Hear: Genentech, Inc.: Current Employment;F. Hoffmann-La Roche Ltd: Current holder of individual stocks in a privately-held company. Sehn: Novartis: Consultancy;Debiopharm: Consultancy;Genmab: Consultancy. OffLabel Disclosure: Mosunetuzumab is a CD20xCD3 bispecific antibody that redirects T cells to engage and eliminate malignant B cells. Mosunetuzumab is an investigational agent.

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