Personal GHG emissions accounting and the driving forces decomposition in the past 10 years

Personal greenhouse gas (PGHG) emissions were crucial for achieving carbon peak and neutrality targets. The accounting methodology and driving forces identification of PGHG emissions were helpful for the quantification and the reduction of the PGHG emissions. In this study, the methodology of PGHG emissions was developed from resource obtaining to waste disposal, and the variations of Shanghainese PGHG emissions from 2010 to 2020 were evaluated, with the driving forces analysis based on Logarithmic Mean Divisia Index (LMDI) model. It showed that the emissions decreased from 3796.05 (2010) to 3046.87 kg carbon dioxides (CO2) (2014) and then increased to 3411.35 kg CO2 (2018). The emissions from consumptions accounted for around 62.1% of the total emissions, and that from waste disposal were around 3.1%, which were neglected in most previous studies. The PGHG emissions decreased by around 0.53 kg CO2 (2019) and 405.86 kg CO2 (2020) compared to 2018 and 2019, respectively, which were mainly affected by the waste forced source separation policy and the COVID-19 pandemic. The income level and consumption GHG intensity were two key factors influencing the contractively of GHG emissions from consumption, with the contributing rate of 169.3% and − 188.1%, respectively. Energy consumption was the main factor contributing to the growth of the direct GHG emissions (296.4%), and the energy GHG emission factor was the main factor in suppressing it (− 92.2%). Green consumption, low carbon lifestyles, green levy programs, and energy structure optimization were suggested to reduce the PGHG emissions. © 2023, The Author(s).

Infrared Spectroscopy Study on Temperature Characteristics of Several Common Antibiotics and Therapeutic COVID-19 Drugs

The far infrared (1 similar to 10 THz) and mid-infrared (400 similar to 4 000 cm(-1)) spectra of six common antibiotics (Ofloxacin capsules, Ofloxacin tablets, Norfloxacin capsules, Azithromycin tablets, Roxithromycin tablets and Levofloxacin hydrochloride tablets), three antiviral drugs for COVID-19 (Ribavirin tablets, Abidol hydrochloride tablets and Chloroquine phosphate tablets) and an expectorant drug (Ambroxol hydrochloride tablets) within shelf-life were studied. The effects of vehicles and another high temperature environment (65 degrees C) on the structure and crystal form of drugs were simulated and fed back to the changes in infrared spectra. After two months of continuous experiments, it was found that the structure and crystal form of other drugs had hardly changed except in ambroxol hydrochloride tablets. When capsule drugs were placed in high-temperature environment for a long time, the epidermis would become brittle and easy to rupture, but the efficacy of internal drugs had hardly changed. Taking fluoroquinolone antibiotics (Ofloxacin and Norfloxacin) as examples, combined with density functional theory (DFT) and the potential energy distribution (PED) method, the theoretical infrared spectra of the two antibiotics monomers, polymers and crystals were calculated by Crystal 14 and Gaussian 16 software with B3LYP/6-311++G(d,p) basis set. The vibrational modes and their contribution rates corresponding to all characteristic peaks were obtained, and the experimental spectrum was accurately identified. It was also found that from monomer to polymer and then to crystal, the stacking force (pi-pi interaction) between lattices accounted for the largest proportion of inter-molecular interaction, more than 90%. Therefore, the theoretical calculation was more consistent with the experimental results only when the crystal with periodic boundary conditions was taken as the initial configuration. The vibrational modes in the far infrared band mainly came from the collective vibration of molecules (vibration accounts for more than 99%, rotation and translation account for less than 1%), and the out-of-plane bending caused by inter-molecular hydrogen bond and Van der Waals force contributes the most, more than 90%. In the mid-infrared band, there were also a certain proportion of inter-molecular interactions. For example, the peaks of norfloxacin at 1 440 cm(-1) and ofloxacin at 1 524 cm(-1) can only be reproduced in the theoretical spectrum with the crystal as the configuration, respectively, from the collective vibration and the stretching of O-H center dot center dot center dot O bonds.

Infrared Spectroscopy Study on Temperature Characteristics of Several Common Antibiotics and Therapeutic COVID-19 Drugs

The far infrared (1~10 THz) and mid-infrared (400~4 000 cm-1) spectra of six common antibiotics (Ofloxacin capsules, Ofloxacin tablets, Norfloxacin capsules, Azithromycin tablets, Roxithromycin tablets and Levofloxacin hydrochloride tablets), three antiviral drugs for COVID-19 (Ribavirin tablets, Abidol hydrochloride tablets and Chloroquine phosphate tablets) and an expectorant drug (Ambroxol hydrochloride tablets) within shelf-life were studied. The effects of vehicles and another high temperature environment (65 ℃) on the structure and crystal form of drugs were simulated and fed back to the changes in infrared spectra. After two months of continuous experiments, it was found that the structure and crystal form of other drugs had hardly changed except in ambroxol hydrochloride tablets. When capsule drugs were placed in high-temperature environment for a long time, the epidermis would become brittle and easy to rupture, but the efficacy of internal drugs had hardly changed. Taking fluoroquinolone antibiotics (Ofloxacin and Norfloxacin) as examples, combined with density functional theory (DFT) and the potential energy distribution (PED) method, the theoretical infrared spectra of the two antibiotics monomers, polymers and crystals were calculated by Crystal 14 and Gaussian 16 software with B3LYP/6-311++G(d,p) basis set. The vibrational modes and their contribution rates corresponding to all characteristic peaks were obtained, and the experimental spectrum was accurately identified. It was also found that from monomer to polymer and then to crystal, the stacking force (π-π interaction) between lattices accounted for the largest proportion of inter-molecular interaction, more than 90%. Therefore, the theoretical calculation was more consistent with the experimental results only when the crystal with periodic boundary conditions was taken as the initial configuration. The vibrational modes in the far infrared band mainly came from the collective vibration of molecules (vibration accounts for more than 99%, rotation and translation account for less than 1%), and the out-of-plane bending caused by inter-molecular hydrogen bond and Van der Waals force contributes the most, more than 90%. In the mid-infrared band, there were also a certain proportion of inter-molecular interactions. For example, the peaks of norfloxacin at 1 440 cm-1 and ofloxacin at 1 524 cm-1 can only be reproduced in the theoretical spectrum with the crystal as the configuration, respectively, from the collective vibration and the stretching of O-H…O bonds. © 2022 Science Press. All rights reserved.

IR Characterizations of Ribavirin, Chloroquine Diphosphate and Abidol Hydrochloride

Since the outbreak of novel coronavirus pneumonia (COVID-19), many research institutes and enterprises at home and abroad have been accelerating the research of COVID-19 (SARS-CoV-2) antibody drugs. However, the research on effective drugs was limited by the drug polymorphisms. The environment of drug production, storage and use also affected the stability of the drug. As a fast, non-destructive testing method, infrared spectroscopy can reflect the differences in drug structure, crystal form and even manufacturing technique to the vibration spectrum, which greatly improves the efficiency of R&D (research and development). In this paper, three clinical trials were considered effective drugs for the treatment of COVID-19: Chloroquine diphosphate, Ribavirin and Abidol hydrochloride. Their far-infrared spectrum (1~10 THz) and mid-infrared spectrum (400~4 000 cm-1) were measured by Fourier transform infrared spectrometer (FTIR). In the far-infrared spectrum, the characteristic peaks of Ribavirin were around 2.01, 2.68, 3.37, 4.05, 4.83, 5.45, 5.92, 6.42 and 7.14 THz;the characteristic peaks of Chloroquine phosphate were near 1.26, 1.87, 2.37, 3.06, 3.78, 5.09 and 6.06 THz;the characteristic peaks of Abidol hydrochloride were located near 2.24, 3.14, 3.72, 4.25 and 5.38 THz. Based on density functional theory, the B3LYP hybrid functional and 6-311++G (d, p) basis sets were selected to analyze the vibrational modes corresponding to all characteristic peaks in the spectrum using Crystal14 and Gaussian 16 software, and the accurate identification of the vibration spectrum was realized. The vibrational modes originated from the molecules' collective vibration in the far infrared region. In the mid-infrared band, below 2 800 cm-1, the vibrational modes mainly came from the in-plane and out-of-plane bending and rocking of the group;Above 2 800 cm-1, the vibrational modes transited to the in-plane stretching of C-H, O-H and N-H bonds. Taking the crystal structure with periodic boundary conditions as the initial configuration of the theoretical calculation would make the calculated spectrum more consistent with the experimental one, especially in the far-infrared band and the low-frequency band of mid-infrared (400~1 000 cm-1). This study was of great significance to deeply understand the pharmaceutical characteristics, drug interactions, control of drug production process, and guide the storage and use of antiviral drugs such as Chloroquine phosphate, Ribavirin and Abidol hydrochloride. © 2022 Science Press. All rights reserved.

Efficacy of Oral Decitabine/Cedazuridine (ASTX727) in the CMML Subgroup from the Ascertain Phase 3 Study

text: Background/Introduction: Chronic Myelomonocytic Leukemia (CMML) is an uncommon MDS/MPN overlap syndrome that has historically been included under the umbrella of myelodysplastic syndromes (MDS) for clinical trial and treatment. As a result, DNA methyltransferase inhibitors (DNMTi) such as decitabine or azacitidine have been the established standard of care for the treatment of CMML. The oral bioavailability of these agents has been limited due to rapid degradation by cytidine deaminase (CDA) in the gut and liver so treatment has required intravenous infusion or subcutaneous injections daily for 5-7 days every month (m) adding significant burden to older cancer patients due to daily time commitment and travel to treatment centers. In the context of pandemic SARS-CoV-2, parenteral therapy also increases contact with medical settings with increased infection risk. Oral decitabine 35 mg/cedazuridine 100 mg (ASTX727) is an oral fixed dose combination of decitabine and the CDA inhibitor cedazuridine that produced equivalent exposure (99%;90% CI 93% to 106%) to IV decitabine 20 mg/m 2 in a randomized cross-over study (Garcia-Manero et al, ASH 2019), and Median overall survival (mOS) for the entire study population in the ASCERTAIN study was approximately 32 months (Savona, 2021). Here, we present outcome data for this study for the enrolled subpopulation of patients with CMML. Methods: We used a randomized cross over design in which patients were randomized in the first 2 cycles 1:1 to either Sequence A: (decitabine 35 mg/ cedazuridine 100 mg in Cycle 1 followed by IV decitabine at 20 mg/m 2 in Cycle 2), or Sequence B: (IV decitabine in Cycle 1 followed by oral decitabine/cedazuridine in Cycle 2). We conducted an intra-patient comparison of decitabine PK (primary PK endpoint: decitabine AUC equivalence over 5 days of dosing). Cycles were repeated every 28 days (unless delays were needed). All patients received oral decitabine/cedazuridine in Cycles 3 and above until disease progression or unacceptable toxicity. Patients were eligible per the FDA-approved label of IV decitabine (MDS patients by FAB classification including CMML, or MDS IPSS Intermediate-1, 2 or high-risk patients). Clinical endpoints were best response according to International Working Group (IWG) 2006 response criteria, transfusion independence for at least 8 or 16 consecutive weeks, overall survival, and safety. Adverse events (AEs) were graded by Common Terminology Criteria for Adverse Events (CTCAE) v 4.03. Results: Of the 133 patients enrolled and treated in ASCERTAIN, 16 (12%) had a diagnosis of CMML with demographics and as follows: median age 71.5 years, 69% Male/31% Female, median weight 87kg (range 65-124), 25% ECOG 0, 75% ECOG 1. Population disease characteristics were: 19% poor or intermediate risk cytogenetics, with median baseline hemoglobin 90 g/L, neutrophils 1.27 X 10 9/L, platelets 84 x 10 9/L, bone marrow blasts 5%, with 38% RBC transfusion dependent. Patients received a median of 7 cycles of therapy (range 3-24). Treatment-emergent adverse events of CTCAE Grade 3 or higher in > 10% of patients, independent of relationship to ASTX727, were cytopenias (neutropenia [69%], thrombocytopenia [63%], anemia [56%], leukopenia [19%]), febrile neutropenia (31%), fatigue (13%). Two patients (12.5%) had Complete Responses (CR), 8 (50%) had marrow CR ([mCR], including 3 (19%) with hematologic improvement (HI);Overall Response rate (ORR) [CR + PR+ mCR + HI] was 75%. Of six patients with baseline RBC transfusion dependence 3 (50%) became transfusion independent. Leukemia-free survival was 28.2 months and after a median follow up of more than 33 months, median overall survival had not been reached. Two patients (13%) went on to Hematopoietic Stem Cell Transplant (HCT). Conclusions: In the overall study, oral decitabine/cedazuridine delivered equivalent PK exposure to 5 days of IV decitabine 20mg/m 2 with a resultant clinical activity safety and efficacy profile in CMML patients consistent with the published literature (e.g Zeidan, et a 2017) and the Phase 2 experience. The use of oral decitabine/cedazuridine is a reasonable approach in CMML patients. References: Garcia-Manero, et al ASH 2019 Savona, et al, Int. MDS Symposium, 2021 Zeidan, et al, Cancer 2017: 3754-3762. [Formula presented] Disclosures: Savona: Geron: Consultancy, Membership on an entity's Board of Directors or advisory committees;CTI: Consultancy, Membership on an entity's Board of Directors or advisory committees;Karyopharm: Consultancy, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees;BMS-Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees;NOVARTIS: Consultancy, Membership on an entity's Board of Directors or advisory committees;Ryvu: Consultancy, Membership on an entity's Board of Directors or advisory committees;Sierra Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees;Taiho: Consultancy, Membership on an entity's Board of Directors or advisory committees;TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;ALX Oncology: Research Funding;Astex: Research Funding;Incyte: Research Funding. McCloskey: Pfizer: Consultancy;Takeda: Consultancy, Speakers Bureau;Incyte: Speakers Bureau;Novartis: Consultancy;COTA: Other: Equity Ownership;BMS: Honoraria, Speakers Bureau;Amgen: Speakers Bureau;Jazz: Consultancy, Speakers Bureau. Griffiths: Boston Biomedical: Consultancy;Celgene/Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding;Abbvie: Consultancy, Honoraria;Taiho Oncology: Consultancy, Honoraria;Genentech: Research Funding;Astex Pharmaceuticals: Honoraria, Research Funding;Takeda Oncology: Consultancy, Honoraria;Novartis: Honoraria;Apellis Pharmaceuticals: Research Funding;Alexion Pharmaceuticals: Consultancy, Research Funding. Yee: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Forma Therapeutics: Research Funding;Geron: Research Funding;Shattuck Labs: Membership on an entity's Board of Directors or advisory committees;Bristol-Myers Squibb/Celgene: Membership on an entity's Board of Directors or advisory committees;F. Hoffmann La Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding;AbbVie: Honoraria;Janssen: Research Funding;Onconova: Research Funding;Genentech: Research Funding;Otsuka: Membership on an entity's Board of Directors or advisory committees;MedImmune: Research Funding;Jazz: Research Funding;Astex: Membership on an entity's Board of Directors or advisory committees, Research Funding;Tolero: Research Funding;Takeda: Membership on an entity's Board of Directors or advisory committees;TaiHo: Membership on an entity's Board of Directors or advisory committees;Pfizer: Membership on an entity's Board of Directors or advisory committees;Paladin: Membership on an entity's Board of Directors or advisory committees. Zeidan: BeyondSpring: Consultancy;Janssen: Consultancy;Boehringer Ingelheim: Consultancy, Research Funding;BioCryst: Other: Clinical Trial Committees;AstraZeneca: Consultancy;Pfizer: Other: Travel support, Research Funding;Kura: Consultancy, Other: Clinical Trial Committees;Incyte: Consultancy, Research Funding;Ionis: Consultancy;Daiichi Sankyo: Consultancy;Epizyme: Consultancy;Novartis: Consultancy, Other: Clinical Trial Committees, Travel support, Research Funding;Loxo Oncology: Consultancy, Other: Clinical Trial Committees;Genentech: Consultancy;Geron: Other: Clinical Trial Committees;Cardiff Oncology: Consultancy, Other: Travel support, Research Funding;BMS: Consultancy, Other: Clinical Trial Committees, Research Funding;Gilead: Consultancy, Other: Clinical Trial Committees;Aprea: Consultancy, Research Funding;Astellas: Consultancy;Astex: Research Funding;Jazz: Consultancy;Jasper: Consu tancy;Amgen: Consultancy, Research Funding;Agios: Consultancy;ADC Therapeutics: Research Funding;Acceleron: Consultancy, Research Funding;AbbVie: Consultancy, Other: Clinical Trial Committees, Research Funding. Al-Kali: Novartis: Research Funding;Astex: Other: Research support to institution. Patel: Agios: Membership on an entity's Board of Directors or advisory committees;Celgene-BMS: Membership on an entity's Board of Directors or advisory committees;PVI: Honoraria. Sabloff: Takeda: Membership on an entity's Board of Directors or advisory committees;BMS: Membership on an entity's Board of Directors or advisory committees;Astellas: Membership on an entity's Board of Directors or advisory committees;Novartis: Membership on an entity's Board of Directors or advisory committees;TaiHo: Membership on an entity's Board of Directors or advisory committees;Jaxx: Membership on an entity's Board of Directors or advisory committees;Abbvie: Membership on an entity's Board of Directors or advisory committees;Pfizer: Membership on an entity's Board of Directors or advisory committees;ROCHE: Membership on an entity's Board of Directors or advisory committees;Celgene: Membership on an entity's Board of Directors or advisory committees. Dao: Astex Pharmaceuticals, Inc.: Current Employment. Fazal: Janssen Oncology: Consultancy, Honoraria, Speakers Bureau;Taiho Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau;Gilead Sciences: Consultancy, Honoraria, Speakers Bureau;Novartis: Consultancy, Honoraria, Speakers Bureau;Agios: Consultancy, Honoraria, Speakers Bureau;Sanofi Genzyme: Consultancy, Honoraria, Speakers Bureau;Takeda: Consultancy, Honoraria, Speakers Bureau;Glaxo Smith Kline: Consultancy, Honoraria, Speakers Bureau;AMGEN: Consultancy, Honoraria, Speakers Bureau;Incyte: Consultancy, Honoraria, Speakers Bureau;Jazz Pharmaceuticals:Consultancy, Honoraria, Speakers Bureau;Bristol Myers Squibb: Consultancy, Honoraria, Speakers Bureau;Stemline Therapeutics: Consultancy, Honoraria, Speakers Bureau;Karyopharm Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau. Odenike: Celgene, Incyte, AstraZeneca, Astex, NS Pharma, AbbVie, Gilead, Janssen, Oncotherapy, Agios, CTI/Baxalta, Aprea: Research Funding;AbbVie, Celgene, Impact Biomedicines, Novartis, Taiho Oncology, Takeda: Consultancy. Kantarjian: Ipsen Pharmaceuticals: Honoraria;Astra Zeneca: Honoraria;Astellas Health: Honoraria;Aptitude Health: Honoraria;Pfizer: Honoraria, Research Funding;Novartis: Honoraria, Research Funding;Jazz: Research Funding;Immunogen: Research Funding;Daiichi-Sankyo: Research Funding;BMS: Research Funding;Ascentage: Research Funding;Amgen: Honoraria, Research Funding;AbbVie: Honoraria, Research Funding;KAHR Medical Ltd: Honoraria;NOVA Research: Honoraria;Precision Biosciences: Honoraria;Taiho Pharmaceutical Canada: Honoraria. DeZern: Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees;Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees;Taiho: Consultancy, Membership on an entity's Board of Directors or advisory committees;Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees. Roboz: Janssen: Research Funding;AbbVie: Consultancy;Actinium: Consultancy;Agios: Consultancy;Amgen: Consultancy;Astex: Consultancy;Astellas: Consultancy;AstraZeneca: Consultancy;Bayer: Consultancy;Blueprint Medicines: Consultancy;Bristol Myers Squibb: Consultancy;Celgene: Consultancy;Daiichi Sankyo: Consultancy;Glaxo SmithKline: Consultancy;Helsinn: Consultancy;Janssen: Consultancy;Jasper Therapeutics: Consultancy;Jazz: Consultancy;MEI Pharma - IDMC Chair: Consultancy;Mesoblast: Consultancy;Novartis: Consultancy;Otsuka: Consultancy;Pfizer: Consultancy;Roche/Genentech: Consultancy. Busque: Novartis: Consultancy. Leber: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Pfizer: Membership on an entity's Board of Directors or advisory committees, peakers Bureau;BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;AMGEN: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;TaiHo: Honoraria, Membership on an entity's Board of Directors or advisory committees;Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Otsuka: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Astellas: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Jazz: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Hao: Astex Pharmaceuticals, Inc.: Current Employment. Keer: Astex Pharmaceuticals, Inc.: Current Employment. Azab: Astex Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees.

Oral Decitabine/Cedazuridine in Patients with Lower Risk Myelodysplastic Syndrome: A Longer-Term Follow-up of from the Ascertain Study

[Formula presented] Background/Introduction: Lower-risk (IPSS low risk and Int-1) myelodysplastic syndromes (MDS) are typically treated supportively to address cytopenias. DNA methyltransferase inhibitors (DNMTi) such as azacitidine and decitabine (DEC) are FDA-approved for higher risk MDS patients (pts), and while the DEC USPI includes IPSS Int-1 pts, it is not widely used in this population. Approved intravenous (IV) or subcutaneous (SC) regimens require 5-7 days of treatment every month burdening older cancer pts due to daily travel and treatment time and may increase potential risk from pandemic SARS-CoV-2 infection. Because DNMTis are rapidly degraded by cytidine deaminase (CDA) in the gut and liver, oral availability has only been recently possible. A randomized study with CC-486, an oral formulation of azacitidine, in the Int-1 population showed a median overall survival (mOS) of approximately 17 months for both placebo and treated patients (Garcia-Manero, 2021). Oral DEC 35 mg/cedazuridine 100 mg (ASTX727) or DEC-C, is an oral fixed dose combination (FDC) of DEC and the CDA inhibitor cedazuridine (CED) resulting in equivalent exposure (99%;90% CI 93% to 106%) to standard IV DEC 20 mg/m 2 for 5 days in an intra-patient randomized cross-over study (Garcia-Manero et al, ASH 2019). Here, we present data on patients with lower risk MDS from that study. Methods: We used a randomized cross over design with pts randomized 1:1 in the first 2 cycles to either Sequence A: (DEC 35 mg/ CED 100 mg in Cycle 1 and IV DEC at 20 mg/m 2 in Cycle 2), or Sequence B (IV DEC in Cycle 1 and oral DEC/CED in Cycle 2). Cycles were repeated every 28 days unless delays were needed, and all patients received oral DEC-C in Cycles 3+ until disease progression or unacceptable toxicity. We conducted an intra-patient comparison of DEC PK (DEC AUC equivalence over 5 days of dosing). Pts were eligible as per the FDA-approved label of IV DEC (MDS pts by FAB classification including CMML, or MDS IPSS Intermediate-1, 2 or high-risk pts). Clinical endpoints were best response as assessed by an independent expert panel according to IWG 2006 response criteria, transfusion independence (TI), overall survival (OS), and safety. Results: Of the 133 pts treated in ASCERTAIN, 69 had a diagnosis of lower-risk MDS (93% Int-1, 7% LR). Median age was 70.0 years (range 45-87), 65% were male, median weight was 84 kg (range 50-127), median baseline hematologic parameters were: hemoglobin 89 g/L (range 69.8-146.5), WBCs 1.50 X 10 9/L (range 0.11-7.1), platelets (plt) 86 x 10 9/L (range 5-703), bone marrow blasts 4% (range 0-18), cytogenetics: 7 (10.1%) poor-risk, 21 (30.4%) intermediate risk, 37 (53.6%) better-risk, 4 (5.7%) missing or not evaluable. 27(39%) of the pts were RBC transfusion dependent (TD) and 6 (9%) plt TD. 17 (25%) had received prior MDS treatment, 3% prior DNMTi. Pts received a median of 9 cycles of therapy (range 1-28). Treatment-emergent adverse events of CTCAE Gr 3 or higher in >10% of pts, independent of relationship to ASTX727, included cytopenias (neutropenia [59%], thrombocytopenia [58%], anemia [48%], leukopenia [26%]), febrile neutropenia (32%), and pneumonia (19%). Sixteen pts (23%) achieved Complete Response (CR), 18 (26%) had marrow CR (mCR), including 9 (13%) with hematologic improvement (HI). Overall Response rate (ORR;CR + PR+ mCR + HI) was 57%. Of those RBC or plt TD at baseline, 13 (48%) became RBC TI and 4 (67%) became plt TI. With approximately 32 months of median follow up, neither median leukemia-free survival (mLFS) nor mOS had been reached (Figure 1). Twelve pts (17%) went on to allogeneic stem cell transplant. Conclusions: Oral decitabine/cedazuridine given as a FDC in MDS pts produced equivalent PK exposure to 20 mg/m 2 IV DEC;in lower risk MDS pts with treatment indicated, the agent was generally well-tolerated with prolonged treatment and could result in mLFS and mOS which exceeds 32 months. This FDC and other dosing regimens of oral DEC-C should be further studied in this patient population. References: Garcia-Mane o, et al, ASH 2019 Savona, et al, Int. MDS Symp. 2021 Garcia-Manero, et al, Phase III, Randomized, Placebo-Controlled Trial of CC-486 (Oral Azacitidine) in Patients with Lower-Risk Myelodysplastic Syndromes. J.Clin.Onc. 2021 39:13, 1426-1436 [Formula presented] Disclosures: McCloskey: Pfizer: Consultancy;Jazz: Consultancy, Speakers Bureau;COTA: Other: Equity Ownership;Incyte: Speakers Bureau;Takeda: Consultancy, Speakers Bureau;Novartis: Consultancy;BMS: Honoraria, Speakers Bureau;Amgen: Speakers Bureau. Griffiths: Alexion Pharmaceuticals: Consultancy, Research Funding;Abbvie: Consultancy, Honoraria;Taiho Oncology: Consultancy, Honoraria;Genentech: Research Funding;Novartis: Honoraria;Takeda Oncology: Consultancy, Honoraria;Astex Pharmaceuticals: Honoraria, Research Funding;Celgene/Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding;Apellis Pharmaceuticals: Research Funding;Boston Biomedical: Consultancy. Yee: Paladin: Membership on an entity's Board of Directors or advisory committees;TaiHo: Membership on an entity's Board of Directors or advisory committees;Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Genentech: Research Funding;Geron: Research Funding;Janssen: Research Funding;Jazz: Research Funding;MedImmune: Research Funding;Onconova: Research Funding;Tolero: Research Funding;AbbVie: Honoraria;Bristol-Myers Squibb/Celgene: Membership on an entity's Board of Directors or advisory committees;Otsuka: Membership on an entity's Board of Directors or advisory committees;Shattuck Labs: Membership on an entity's Board of Directors or advisory committees;Pfizer: Membership on an entity's Board of Directors or advisory committees;Takeda: Membership on an entity's Board of Directors or advisory committees;F. Hoffmann La Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding;Forma Therapeutics: Research Funding;Astex: Membership on an entity's Board of Directors or advisory committees, Research Funding. Zeidan: Novartis: Consultancy, Other: Clinical Trial Committees, Travel support, Research Funding;Genentech: Consultancy;Ionis: Consultancy;Astellas: Consultancy;Epizyme: Consultancy;AbbVie: Consultancy, Other: Clinical Trial Committees, Research Funding;Jasper: Consultancy;Cardiff Oncology: Consultancy, Other: Travel support, Research Funding;BeyondSpring: Consultancy;Loxo Oncology: Consultancy, Other: Clinical Trial Committees;Janssen: Consultancy;Acceleron: Consultancy, Research Funding;AstraZeneca: Consultancy;Kura: Consultancy, Other: Clinical Trial Committees;Gilead: Consultancy, Other: Clinical Trial Committees;Agios: Consultancy;Daiichi Sankyo: Consultancy;Boehringer Ingelheim: Consultancy, Research Funding;Geron: Other: Clinical Trial Committees;BMS: Consultancy, Other: Clinical Trial Committees, Research Funding;BioCryst: Other: Clinical Trial Committees;Pfizer: Other: Travel support, Research Funding;Aprea: Consultancy, Research Funding;ADC Therapeutics: Research Funding;Jazz: Consultancy;Incyte: Consultancy, Research Funding;Amgen: Consultancy, Research Funding;Astex: Research Funding. Al-Kali: Astex: Other: Research support to institution;Novartis: Research Funding. Patel: Celgene-BMS: Membership on an entity's Board of Directors or advisory committees;PVI: Honoraria;Agios: Membership on an entity's Board of Directors or advisory committees. Sabloff: Pfizer: Membership on an entity's Board of Directors or advisory committees;Novartis: Membership on an entity's Board of Directors or advisory committees;Astellas: Membership on an entity's Board of Directors or advisory committees;Takeda: Membership on an entity's Board of Directors or advisory committees;ROCHE: Membership on an entity's Board of Directors or advisory committees;TaiHo: Membership on an entity's Board of Directors or advisory committees;Jaxx: Membership on an entity's Board of Directors or advisory committees;Celgene: Membership on an entity's Board of Directors or advisory ommittees;BMS: Membership on an entity's Board of Directors or advisory committees;Abbvie: Membership on an entity's Board of Directors or advisory committees. Dao: Astex Pharmaceuticals, Inc.: Current Employment. Fazal: Taiho Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau;Stemline Therapeutics: Consultancy, Honoraria, Speakers Bureau;Sanofi Genzyme: Consultancy, Honoraria, Speakers Bureau;Novartis: Consultancy, Honoraria, Speakers Bureau;Karyopharm Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau;Jazz Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau;Janssen Oncology: Consultancy, Honoraria, Speakers Bureau;Incyte: Consultancy, Honoraria, Speakers Bureau;Glaxo Smith Kline: Consultancy, Honoraria, Speakers Bureau;Gilead Sciences: Consultancy, Honoraria, Speakers Bureau;Bristol Myers Squibb: Consultancy, Honoraria, Speakers Bureau;AMGEN: Consultancy, Honoraria, Speakers Bureau;Agios: Consultancy, Honoraria, Speakers Bureau;Takeda: Consultancy, Honoraria, Speakers Bureau. Odenike: AbbVie, Celgene, Impact Biomedicines, Novartis, Taiho Oncology, Takeda: Consultancy;Celgene, Incyte, AstraZeneca, Astex, NS Pharma, AbbVie, Gilead, Janssen, Oncotherapy, Agios, CTI/Baxalta, Aprea: Research Funding. Kantarjian: AbbVie: Honoraria, Research Funding;Novartis: Honoraria, Research Funding;Ascentage: Research Funding;Pfizer: Honoraria, Research Funding;BMS: Research Funding;Daiichi-Sankyo: Research Funding;Amgen: Honoraria, Research Funding;Ipsen Pharmaceuticals: Honoraria;Jazz: Research Funding;Astellas Health: Honoraria;Immunogen: Research Funding;Astra Zeneca: Honoraria;Aptitude Health: Honoraria;KAHR Medical Ltd: Honoraria;NOVA Research: Honoraria;Precision Biosciences: Honoraria;Taiho Pharmaceutical Canada: Honoraria. DeZern: Takeda: Consultancy, Membership on an entity's Board of Directors or advisorycommittees;Taiho: Consultancy, Membership on an entity's Board of Directors or advisory committees;Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees;Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees. Roboz: Novartis: Consultancy;Mesoblast: Consultancy;Jasper Therapeutics: Consultancy;Jazz: Consultancy;MEI Pharma - IDMC Chair: Consultancy;Daiichi Sankyo: Consultancy;Otsuka: Consultancy;Bristol Myers Squibb: Consultancy;Blueprint Medicines: Consultancy;Bayer: Consultancy;AstraZeneca: Consultancy;Astellas: Consultancy;Astex: Consultancy;Amgen: Consultancy;Agios: Consultancy;Actinium: Consultancy;AbbVie: Consultancy;Janssen: Research Funding;Celgene: Consultancy;Glaxo SmithKline: Consultancy;Helsinn: Consultancy;Janssen: Consultancy;Pfizer: Consultancy;Roche/Genentech: Consultancy. Busque: Novartis: Consultancy. Leber: Astellas: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Otsuka: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;TaiHo: Honoraria, Membership on an entity's Board of Directors or advisory committees;AMGEN: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Jazz: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Hao: Astex Pharmaceuticals, Inc.: Current Employment. Keer: Astex Pharmaceuticals, Inc.: Current Employment. Azab: Astex Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees. Savona: Geron: Consultancy, Membership on an entity's Board of Directors or advisory committees;Karyopharm: Cons ltancy, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees;CTI: Consultancy, Membership on an entity's Board of Directors or advisory committees;BMS-Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees;NOVARTIS: Consultancy, Membership on an entity's Board of Directors or advisory committees;Ryvu: Consultancy, Membership on an entity's Board of Directors or advisory committees;Sierra Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees;Taiho: Consultancy, Membership on an entity's Board of Directors or advisory committees;TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;ALX Oncology: Research Funding;Astex: Research Funding;Incyte: Research Funding.

Application evaluation of a rapid fluorescence quantitative PCR method for the detection of SARS-CoV-2

Objective: To establish and evaluate a rapid nucleic acid detection method for SARS-CoV-2 based on COYOTE® Flash20 real-time fluorescent quantitative PCR instrument. Methods: A rapid reaction system was constructed by using specific primer and probe sets targeting ORF1ab and N gene of SARS-CoV-2, and the sensitivity and specificity of the system were verified. At the same time, 108 clinical samples of COVID-19 were used to evaluate the application of this method. Results: The detection method did not require nucleic acid extraction, and the manual operation time was only one minute. After the sample was sent to the system, the test could be completed in 30 minutes. The detection limit of this method was 4×102 copies/ml. It had no cross-reactivity with other human coronaviruses (including HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1, SARS-CoV and MERS-CoV) and other respiratory viruses. The evaluation of clinical sample application showed that the total coincidence rate with the conventional RT-qPCR which required nucleic acid extraction was 98.15%. Conclusions: Through the application evaluation of the rapid fluorescent quantitative PCR method of SARS-CoV-2, it was found that the method was simple, fast, specific and sensitive, and it was suitable for real-time and rapid detection needs in varieties of situations. Copyright © 2021 by the Chinese Medical Association.

Hospital-onset COVID-19 infection surveillance systems: a systematic review.

Hospital-onset COVID-19 infections (HOCIs) are associated with excess morbidity and mortality in patients and healthcare workers. The aim of this review was to explore and describe the current literature in HOCI surveillance. Medline, EMBASE, the Cochrane Database of Systematic Reviews, the Cochrane Register of Controlled Trials, and MedRxiv were searched up to 30 November 2020 using broad search criteria. Articles of HOCI surveillance systems were included. Data describing HOCI definitions, HOCI incidence, types of HOCI identification surveillance systems, and level of system implementation were extracted. A total of 292 citations were identified. Nine studies on HOCI surveillance were included. Six studies reported on the proportion of HOCI among hospitalized COVID-19 patients, which ranged from 0 to 15.2%. Six studies provided HOCI case definitions. Standardized national definitions provided by the UK and US governments were identified. Four studies included healthcare workers in the surveillance. One study articulated a multimodal strategy of infection prevention and control practices including HOCI surveillance. All identified HOCI surveillance systems were implemented at institutional level, with eight studies focusing on all hospital inpatients and one study focusing on patients in the emergency department. Multiple types of surveillance were identified. Four studies reported automated surveillance, of which one included real-time analysis, and one included genomic data. Overall, the study quality was limited by the observational nature with short follow-up periods. In conclusion, HOCI case definitions and surveillance methods were developed pragmatically. Whilst standardized case definitions and surveillance systems are ideal for integration with existing routine surveillance activities and adoption in different settings, we acknowledged the difficulties in establishing such standards in the short-term.

Investigating the impact of COVID-19 on primary care antibiotic prescribing in North West London across two epidemic waves

OBJECTIVES: We investigated the impact of COVID-19 and national pandemic response on primary care antibiotic prescribing in London. METHODS: Individual prescribing records between 2015 and 2020 for 2 million residents in north west London were analysed. Prescribing records were linked to SARS-CoV-2 test results. Prescribing volumes, in total, and stratified by patient characteristics, antibiotic class and AWaRe classification, were investigated. Interrupted time series analysis was performed to detect measurable change in the trend of prescribing volume since the national lockdown in March 2020, immediately before the first COVID-19 peak in London. RESULTS: Records covering 366 059 patients, 730 001 antibiotic items and 848 201 SARS-CoV-2 tests between January and November 2020 were analysed. Before March 2020, there was a background downward trend (decreasing by 584 items/month) in primary care antibiotic prescribing. This reduction rate accelerated to 3504 items/month from March 2020. This rate of decrease was sustained beyond the initial peak, continuing into winter and the second peak. Despite an overall reduction in prescribing volume, co-amoxiclav, a broad-spectrum "Access" antibiotic, prescribing rose by 70.1% in patients aged 50 and older from February to April. Commonly prescribed antibiotics within 14 days of a positive SARS-CoV-2 test were amoxicillin (863/2474, 34.9%) and doxycycline (678/2474, 27.4%). This aligned with national guidelines on management of community pneumonia of unclear cause. The proportion of "Watch" antibiotics used decreased during the peak in COVID-19. DISCUSSION: A sustained reduction in community antibiotic prescribing has been observed since the first lockdown. Investigation of community-onset infectious diseases and potential unintended consequences of reduced prescribing is urgently needed.

Epidemiological characteristics and transmission routes of COVID-19 asymptomatic infected patients in Shaanxi Province

Objective: To assess the epidemiological characteristics and transmission risk of asymptomatic COVID-19 infection in Shaanxi Province. Methods: A dense population database of COVID-19 cases in Shaanxi Province was constructed as of March 26, 2020, and 28 asymptomatic infected patients were selected through case epidemiological investigation report for descriptive analysis. Results: In Shaanxi Province, the majority of asymptomatic COVID-19 infections were in the 20-59 years old group, and women took up a higher proportion than men. 82.14% of asymptomatic infections were found in the centralized isolation state. Nearly 80% of asymptomatic infections and confirmed cases were mainly exposed by living together in the family. The median number of days from last contact with the source of infection for all asymptomatic infected persons was 13, with 3 (10.71%) showing clinical symptoms. Epidemiological investigations showed that asymptomatic infections could spread as a result of shared family life. Conclusion: At present, imported cases in Shaanxi Province continue to exist. Considering the concealed transmission of asymptomatic infections, prevention and control work is still facing challenges. © 2021, Editorial Board of Journal of Xi'an Jiaotong University (Medical Sciences). All right reserved.

Analysis of the path from discovery of novel coronavirus disease 2019 cases to its diagnosis in Shaanxi Province

Objective: To explore the problems and experience in the prevention and control of novel coronavirus disease 2019 (COVID-19) by analyzing the path from its discovery to its diagnosis in Shaanxi Province. Methods: We collected the important data of COVID-19 epidemic situation in Shaanxi Province as of March 26, 2020, the trajectory of the diagnosed cases, contact history, close contacts and other important information for a descriptive epidemiological analysis. Results: Totally 72.65% (178/245) of the confirmed COVID-19 cases in Shaanxi Province were not in isolation or management at the time of onset, which resulted in an infection rate of 1.37% in close-knit populations. The duration between the onset of local COVID-19 cases in Shaanxi and the delay in confirmed diagnosis was relatively long (6.30 days), and the mean incubation period was 7.27 days. The delay time (7.29 days) between onset and diagnosis of preepidemic cases was longer than that (6.19 days) of later epidemic cases. Conclusion: According to the epidemic situation, we should gradually sort out the loopholes in previous work and at the same time make timely evaluation of the new problems arising under the new situation and constantly adjust the prevention and control strategies. © 2020, Editorial Board of Journal of Xi'an Jiaotong University (Medical Sciences). All right reserved.

[Typical case analysis of COVID-19 cluster epidemic in Shaanxi, 2020].

Objective: By analyzed the transmission patterns of 4 out of the 51 COVID-19 cluster cases in Shaanxi province to provide evidences for the COVID-19 control and prevention. Methods: The epidemiological data of RT-PCR test-confirmed COVID-19 cases were collected. Transmission chain was drawn and the transmission process was analyzed. Results: Cluster case 1 contained 13 cases and was caused by a family of 5 who traveled by car to Wuhan and returned to Shaanxi. Cluster case 2 had 5cases and caused by initial patient who participated family get-together right after back from Wuhan while under incubation period. Cluster case 3 contained 10 cases and could be defined as nosocomial infection. Cluster case 4 contained 4 cases and occurred in work place. Conclusion: Higher contact frequency and smaller places were more likely to cause a small-scale COVID-19 cluster outbreak, with potential longer incubation period. COVID-19 control strategies should turn the attention to infection prevention and control in crowded places, management of enterprise resumption and prevention of nosocomial infection.

[Analysis of transmission characteristics of COVID-19 in Shaanxi Province].

A total of 245 cases of COVID-19 in Shaanxi Province reported in the China information system for disease control and prevention as of February 24, 2020 were selected as the research objects, the cases are divided into imported cases (116 cases, 47.3%) and local cases (129 cases, 52.7%), their basic characteristics, time distribution, transmission mode, intergenerational interval and latent period transmission are analyzed. The age of local cases [(51.74±15.67) years old], female patients (69 cases, 53.5%), housework and retired staff (40 cases, 31.0%), and patients isolated at the time of onset (50 cases, 38.8%) were higher than imported cases, respectively[(40.66±15.41) years old, (45 cases, 38.8%), (21 cases, 18.1%), (17 cases, 14.6%)] (P values were < 0.05); The infection rate was 0.8% (31/3 666) in close contacts with local cases, which was lower than imported cases 2.0% (69/3 435) (P<0.001); The main source of infection in local cases was relatives (70 cases, 54.3%), and the main way of infection was living together and party (90 cases, 69.8%); the proportion of latent period transmission in our province was 15.5% (20 cases), and the interval between the second-generation case and the source of infection was about 4 days, and the interval between generations was about 6 days. In summary, the main way of infection of local cases in Shaanxi Province was living together and party, there were a certain proportion of latent period transmission cases at present, it's suggested that the investigation of close contacts should be started 4 days or earlier before the onset of the case.

[Epidemiological characteristics of COVID-19 in Shaanxi province].

Objective: To understand the incidence trend and epidemiological characteristics of COVID-19 in Shaanxi province. Methods: The incidence data of COVID-19 reported in Shaanxi as of 22 February, 2020 were collected for an epidemiological descriptive analysis. Results: A total of 245 confirmed cases of COVID-19 were reported in Shaanxi. Most cases were mild (87.76%). As time passed, the areas where confirmed cases were reported continued to increase. The case number in Xi'an was highest, accounting for nearly half of the total reported cases in the province. The epidemic pattern in Shaanxi had gradually shifted from imported case pattern to local case pattern, and the transmission of local cases was mainly based on family cluster transmission. The confirmed cases from different sources had caused the secondary transmission in Shaanxi. After February 7, the number of reported cases began to fluctuate and decrease stably, indicating a decrease-to-zero period. Conclusions: At present, the overall epidemic of COVID-19 in Shaanxi has gradually been mitigated. However, considering the approaching of return to work and study and the increasing of imported cases from other countries, the prevention and control of COVIS-19 in Shaanxi will face new challenges.