ABSTRACT
Delivery of self-amplifying mRNA (SAM) has high potential for infectious disease vaccination due to its self-adjuvanting and dose-sparing properties. Yet a challenge is the susceptibility of SAM to degradation and the need for SAM to reach the cytosol fully intact to enable self-amplification. Lipid nanoparticles are successfully deployed at incredible speed for mRNA vaccination, but aspects such as cold storage, manufacturing, efficiency of delivery, and the therapeutic window can benefit from further improvement. To investigate alternatives to lipid nanoparticles, a class of >200 biodegradable end-capped lipophilic poly(beta-amino ester)s (PBAEs) that enable efficient delivery of SAM in vitro and in vivo as assessed by measuring expression of SAM encoding reporter proteins is developed. The ability of these polymers to deliver SAM intramuscularly in mice is evaluated, and a polymer-based formulation that yields up to 37-fold higher intramuscular (IM) expression of SAM compared to injected naked SAM is identified. Using the same nanoparticle formulation to deliver a SAM encoding rabies virus glycoprotein, the vaccine elicits superior immunogenicity compared to naked SAM delivery, leading to seroconversion in mice at low RNA injection doses. These biodegradable nanomaterials may be useful in the development of next-generation RNA vaccines for infectious diseases.Copyright © 2023 The Authors. Advanced Therapeutics published by Wiley-VCH GmbH.
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As with past pandemics of influenza, COVID-19 tore through US prisons and jails;however, the COVID-19 pandemic, uniquely, has led to more health research on carceral systems than has been seen to date. Herein, we review the data on its impact on incarcerated people, correctional officers, health systems, and surrounding communities. We searched medical, sociological, and criminology databases from March 2020 through February 2022 for studies examining the intersection of COVID-19, prisons and jails, and health outcomes, including COVID-19 incidence, prevalence, hospitalizations, and vaccination. Our scoping review identified 77 studies-the bulk of which focus on disease epidemiology in carceral systems, with a small minority that focuses on the efficacy or effectiveness of prevention and mitigation efforts, including testing, vaccination, and efforts to depopulate correctional facilities. We highlight areas for future research, including the experiences of incarcerated people and correctional staff, unanticipated health effects of prolonged quarantine, excess deaths due to delays in healthcare, and experimental studies on vaccine uptake and testing in correctional staff. These studies will enable a fuller understanding ofCOVID-19 and help stem future pandemics.
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In the post-COVID era, the prevalence of "fandom nationalism" on Chinese social media has led to the development of two distinct attitudes toward Squid Game among Chinese netizens. Some nationalist netizens are dedicated to accusing Squid Game of plagiarism or dismissing it as a "cultural invasion." Another group of fans, due to the ever-tightening Chinese Internet governance, use fandom nationalism as a disguise to protect themselves against cyberbullying by declaring an anti-Korean political stance before posting positive comments about Squid Game. Therefore, two such divergent attitudes eventually led to a negotiation between fan culture and state power, where on the one hand fandom nationalistic practices were accepted by the mainstream for party-state propaganda, but on the other, in order to prevent being censored, fan culture had to be subordinated to the state's governance.
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Objective: The ongoing COVID-19 pandemic has been associated with greater risk of infection and severe complication in solid organ transplant recipients compared to the general population, yet sparse data exists on the effect of COVID-19 on uterus transplant (UTx) recipients. Though immunosuppressed individuals, including organ transplant recipients, experience higher rates of morbidity and mortality following COVID-19 infection, vaccination for COVID-19 has been shown to effectively reduce mortality for these patients. Despite these encouraging results, and statements from professional societies including ASRM recommending vaccination, vaccine hesitancy remains elevated in the infertility population. The goal of this report is to provide details regarding COVID-19 infection and vaccination rates in UTx recipients in the US. Material(s) and Method(s): We performed a retrospective cohort analysis on individuals who have undergone UTx as of March 2021 in the US. Five UTx recipients at two centers (Baylor Scott and White, Dallas, Texas, and Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania) were diagnosed with COVID-19 infection as defined by the presence of a positive SARS-CoV-2 on reverse transcriptase-polymerase chain reaction (RT-PCR) testing from a nasopharyngeal swab. Data collected included demographic features, transplant history, transplant-related complications, vaccination status and pregnancy history. Result(s): The median time from transplant to diagnosis of COVID-19 was 22.8 months. Despite the availability of the COVID-19 vaccine, only one out of 5 UTx recipients was vaccinated at the time of diagnosis. Two recipients were pregnant at the time of diagnosis, one in the first trimester and one in the second trimester of pregnancy. One recipient experienced COVID reinfection three months following the first infection. All COVID positive UTx recipients experienced no or mild symptoms;one recipient was asymptomatic, 4 had nasal congestion, 2 had headaches, and one patient was febrile. Four recipients received Casirivimab-imdevimab. In 80% of patients, no changes were made to patients' immunosuppression regimens. Conclusion(s): All UTx recipients who were diagnosed with COVID-19 infection as of 3/2021 recovered without complications. As in other infertility patients, vaccine hesitancy remains a significant concern despite the UTx population having a higher risk of severe disease. Data continues to accrue demonstrating the safety of vaccination in pregnancy, and communication of these results to the UTx population is essential to promote maternal and child health. Impact Statement: This data provides reassuring information regarding outcomes for COVID-19 infection in UTx population;however also demonstrate that similar to other pregnant patients or patients with infertility, vaccine hesitancy remains a significant issue. Copyright © 2022
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BACKGROUND: Safety net health care systems (which disproportionately serve racial/ethnic minority, low-income, and/or Limited English Proficient (LEP) populations) care for patients who face a multilevel “digital divide.” The transition to telemedicine prompted by the Coronavirus-19 disease (COVID- 19) pandemic facilitated continuity of care in some settings. However, most safety net health systems were left ill-prepared to address challenges to digital uptake among their patients, individuals who already face language and literacy barriers that negatively impact health access and health outcomes. Because there is little evidence on telemedicine implementation strategies in safety nets, we examined perspectives from leadership and frontline healthcare workers in the Los Angeles County Department of Health Services (LAC DHS), the second largest safety net in the United States, regarding facilitators and barriers for effective and patient-centered telemedicine implementation in a safety net setting. METHODS: We conducted 20 in-depth interviews with LAC DHS physicians, nurses, medical/nursing directors, and administrative leadership between October 2020 and December 2020. Interview scripts included questions about telemedicine experiences, technology, staff resources, needs, and facilitators for their implementation, (focusing on video visits). Qualitative analyses involved a deductive approach, with thematic summaries of transcript content using Atlas.ti software. RESULTS: Each of the 5 major LAC DHS centers (encompassing diverse health settings across all of Los Angeles county) were represented among the participants. Based on these interviews, a process map was developedoutlining the numerous staff and patient steps needed to achieve a single LAC DHS telemedicine video visit, alongside identified facilitators and barriers. Themes surrounding telemedicine implementation were identified at the patient, clinic/provider, health system levels with accompanying exemplar quotations. These included: preparedness for digital access and utilization (patient), staff empowerment to implement visits (clinic/provider), telemedicine technology infrastructure (system), among others. CONCLUSIONS: Telemedicine implementation in the safety net setting will require a team-based approach, and patient, clinic, and health system level themes must be considered when disseminating telemedicine services across safety net settings. In particular, participants emphasized prioritizing “hightouch” efforts to enroll patients in their health portal as an entry to digital health engagement/education, and facilitating access to telemedicine visits. Participants also highlighted robust workflows, having defined staff telemedicine “champions,” and multidisciplinary teams that could focus on telemedicine access for patients. Future research will also need to focus on safety net patients' experiences with telemedicine access and quality.
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INTRODUCTION: During the Sars-CoV-2 pandemic, Endoscopic Endonasal Surgery (EES) is feared to be a high-risk procedure for transmission of the COVID-19 virus. Nonetheless, data are lacking regarding the management of EES during this pandemic. METHODS: A web-based survey of skull base surgeons worldwide was conducted.Different practices by geographical regions and COVID-19 prevalence were analyzed. RESULTS: 135 unique responses were collected. Regarding the use of personal protection equipment (PPE), North America reported using more powered air-purifying respirators (PAPR) and Asia/Europe using more standard precautions. North America and Europe resorted more to reverse transcriptase polymerase chain reaction (RT-PCR) for screening asymptomatic patients. High prevalence countries showed a higher use of PAPR. The medium prevalence group reported lower RT-PCR testing for symptomatic cases and the high prevalence group used it significantly more in asymptomatic cases. 19 respondents reported healthcare personnel transmission of COVID-19 from EES, with a higher rate of transmission among countries classified as having a medium prevalence of COVID-19. These specific respondents (medium prevalence) also reported a lower use of airborne PPE. In the cases of healthcare transmission, the patient was reportedly asymptomatic 32% of the time. CONCLUSION: This survey gives an overview of EES practices during the Sars-CoV-2 pandemic. Intensified preoperative screening, even in asymptomatic patients, RT-PCR for all symptomatic cases, and an increased use of airborne PPE is associated with decreased reports of COVID-19 transmission during EES.
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BACKGROUND: BPDCN is a rare, aggressive hematologic malignancy characterized by historically poor overall survival and limited therapeutic options. Despite the recent approval of tagraxofusp-erzs for BPDCN, outcomes remain suboptimal for many patients. Additionally, patients with BPDCN are older and often have co-morbidities at baseline, preventing them from receiving tagraxofusp-erzs. Therefore, novel therapies are needed in the frontline setting for patients with BPDCN. Overexpression of CD123 (IL-3Rα) is present in all BPDCN cases, thereby establishing this surface marker as a target for therapeutic intervention. IMGN632 is a CD123-targeting ADC, comprised of a high-affinity anti-CD123 antibody coupled to a DNA-alkylating payload of the novel IGN (indolinobenzodiazepine pseudodimer) class. IMGN632 has demonstrated favorable safety and promising clinical activity in relapsed/refractory (R/R) BPDCN [Blood (2020) 136 (Supplement 1): 11-13], leading to the FDA granting IMGN632 Breakthrough Therapy Designation (BTD) for R/R BPDCN (Oct 2020). Following BTD and alignment with FDA, a pivotal cohort in frontline (no prior systemic treatment) BPDCN patients was initiated in addition to a continuing cohort of patients with R/R disease, where we have enrolled 33 patients to date. Here we report the initial experience of three frontline patients who are not part of the pivotal cohort. METHODS: IMGN632 was administered IV at a dose of 0.045 mg/kg on day 1 of a 21-day cycle to all patients. Efficacy was assessed using modified Severity Weighted Assessment Tool (for skin lesions), PET/CT, and blast percentage in bone marrow aspirates. The response criteria were adapted from established BPDCN criteria (Pemmaraju NEJM 2019). RESULTS: Three patients with frontline BPDCN (no prior systemic therapy) received IMGN632. All three of these frontline patients achieved a clinical complete remission (CRc). Patient 1 was a 79yo woman who presented with skin, nodal, and extensive bone marrow disease (80% involvement). After one dose of IMGN632, she cleared her bone marrow (0%), and after 3 cycles, her nodal lesions and skin lesions resolved to achieve a CRc. Upon complete response, treatment was held due to patient co-morbidities. With just 3 cycles of IMGN632, this patient achieved duration of response (DOR) of 10.7 months without further therapy. Patient 2 was a 67yo man who had extensive skin disease covering >20% of the body;over several cycles, he achieved a PR then a CRc and bridged to an allogeneic stem cell transplant (SCT). The patient achieved a DOR of 13.5 months, with no evidence of disease relapse when he died from graft versus host disease. Patient 3 was a 66yo woman who presented with extensive skin and nodal lesions. After improvement over 4 cycles, she achieved a CRc with clearing of most of her skin lesions and all nodal lesions. Unfortunately, while still in CRc, the patient died of COVID-19 pneumonia, with a DOR of 3.7 months. CONCLUSION: Administration of IMGN632 to frontline BPDCN patients resulted in clinical complete remission in the initial three patients with durable responses in the two non-COVID impacted patients. None of these patients progressed while on therapy, and one patient successfully bridged to SCT. Enrollment continues in the pivotal frontline and R/R cohorts. (BPDCNtrial.com;NCT03386513).
ABSTRACT
Purpose of Study Despite the tremendous success of SARSCoV- 2 vaccines, breakthrough infections occur and are being recognized with increasing frequency. It is unclear whether breakthrough infections are the result of host and/or viral factors. We examined clinical and viral genomic data from patients with SARS-CoV-2 infection after vaccination to elucidate factors contributing to breakthrough. Methods Used This study was conducted in the Emory Healthcare (EHC) System. Patients with vaccine breakthrough infection, defined as a positive PCR test ≥14 days after the final dose of an FDA approved vaccine, were identified by both routine surveillance and notification by treating clinicians. Vaccination status was obtained from the Georgia Registry of Immunization Transactions and Services records by the Georgia Emerging Infections Program. Clinical information was derived from electronic medical records and was compared to data from 2-3 matched controls per case. Residual SARS-CoV-2 positive nasopharyngeal (NP) samples were collected and underwent RNA extraction. SARSCoV- 2 genome sequencing was performed using random-primer cDNA synthesis, Nextera XT library preparation, and Illumina sequencing. Summary of Results Forty vaccine breakthrough cases were identified between March 22 and July 16, 2021. The median time from final vaccine dose to positive COVID-19 test was 91 days (range 15-163). Compared to 94 controls, vaccine breakthrough cases were significantly older (median 57.5 years vs 42.0 years, p<.0001). Individuals over 60 accounted for half of all breakthrough cases, and individuals over 40 accounted for 80%. Immunosuppressed individuals represented 37.5% of breakthrough cases compared to 25% of unvaccinated controls. Rates of symptomatic infection and severe disease leading to hospitalization were similar between cases and controls. There was no difference in SARS-CoV-2 RT-PCR cycle threshold (Ct) between cases (n=32, median Ct=20.7, interquartile range (IQR)- 10.3) and controls (n=94, median Ct=24.0, IQR= 7.0;p=0.34). SARS-CoV-2 genome sequences from 24 cases were compared to 116 baseline surveillance sequences from unvaccinated EHC patients. There was no distinct phylogenetic clustering of vaccine breakthrough cases, and their sequences belonged to the predominant lineage of the time. From March 22-June 19, B.1.1.7 (alpha) accounted for 78% of breakthrough infections and 77% of surveillance sequences. From June 20-July 16, B.1.617.2 (delta) accounted for 86% of breakthrough infections and 72% of surveillance sequences. No spike mutations or deletions were associated with vaccine breakthrough infections. Conclusions Overall, our findings suggest that host factors, such as older age and immunosuppression, play a more important role than viral factors in SARS-CoV-2 vaccine breakthrough infections. Further studies are needed to understand the potential impacts of waning immunity or poor immunogenicity in individuals who experience vaccine breakthrough infections.
ABSTRACT
Background: Acute myeloid leukemia (AML) is driven by aberrant leukemic stem cells (LSCs) that initiate and sustain malignancy. To circumvent resistance to therapy, combination therapies with additive mechanisms of action are needed. CD70, a tumor necrosis factor receptor ligand, and its receptor CD27 are expressed on LSCs and AML blasts, but not on hematopoietic stem cells. Cusatuzumab, a high-affinity humanized monoclonal anti-CD70 antibody, kills CD70-expressing cells by Fc domain-mediated effector functions and is a potent inhibitor of CD70-CD27 signaling. Here we report initial results of a study of cusatuzumab in combination with the current standard of care therapy, venetoclax plus azacitidine (CVA), in patients with untreated AML (de novo or secondary) ineligible for intensive chemotherapy due to age ≥75 years or medical comorbidities. Methods: The primary objective of this open label, multicenter, phase 1b study was to assess safety and tolerability of CVA. Key secondary objectives included response rate per ELN 2017 criteria and time to response. Patients received cusatuzumab 10 or 20 mg/kg IV on Day 3 and Day 17, a 3-day ramp-up of venetoclax (100, 200, and 400 mg PO) followed by 400 mg daily dosing, and azacitidine 75 mg/m 2 SC or IV on Days 1-7 of each 28-day cycle. Results: Based on data through Jul 9, 2021, 44 patients enrolled with median age 75 years (range 32-89), 36.4% had secondary AML, 40.9% had an ECOG performance status of 2, and ELN risk was favorable, intermediate and adverse in 18.2%, 20.5% and 61.4%, respectively. All patients received 20 mg/kg cusatuzumab except for 3 patients who received a starting dose of 10 mg/kg with the option to escalate to 20 mg/kg. Of these 3 patients, 1 escalated to 20 mg/kg. At a median follow-up of 29.1 weeks, the median number of treatment cycles was 4.0 (range 1.0-11.0). Grade 3 or above TEAEs were reported in 97.7% of patients;the most common (reported in ≥10%) were neutropenia (68.2%), thrombocytopenia (65.9%), febrile neutropenia (36.4%), anemia (34.1%), leukopenia (29.5%), sepsis (27.3%), and lymphopenia (15.9%). Treatment-emergent serious adverse events (SAEs) were reported in 75% of patients;the most common (reported in at least ≥5%) were febrile neutropenia (27.3%), sepsis (22.7%), COVID-19 (6.8%), and thrombocytopenia (6.8%). Treatment-emergent SAEs of grade ≥3 were reported in 72.7% of the patients. Infusion-related reactions (IRRs) were reported for 11.4% of patients with 2.3% at grade ≥3. Six (13.6%) patients discontinued treatment due to AEs, and 5 (11.4%) TEAEs resulted in death. The mortality rate within 30 days from start of treatment was 4.5%. Table 1 summarizes best response to study treatment. In the intent-to-treat analysis set (n=44) complete remission (CR) rate was 45.5%, while CR + CR with partial hematologic recovery (CRh) + CR with incomplete hematologic recovery (CRi) was 77.3%;MLFS was observed in 11.4% of patients. Of 34 responders (defined as CR, CRi or CRh), 47% were MRD negative by flow cytometry at or after achievement of response. Median time to first response for patients who achieved CR, CRh or CRi was 4.21 (3.0-25.0) weeks. Best response rates in the post-hoc response evaluable analysis set (n=42) that excluded two patients who died before the first disease evaluation were: CR in 47.6%, CR + CRh + CRi in 81.0% and MLFS in 11.9% of patients (Table 1). The majority (97.1%) of responders experienced at least one cycle delay in administration of CVA post response. Conclusions: Cusatuzumab administered in combination with venetoclax and azacitidine to elderly patients with untreated AML was generally well tolerated and demonstrated a safety profile consistent with that previously reported with venetoclax-azacitidine, with the addition of generally manageable IRRs. Response rates support an additive effect of cusatuzumab to the standard of care with potential for improved clinical outcomes. However, further clinical trials are needed for validation of these initial results. HK and GB contributed equally to this publ cation. [Formula presented] Disclosures: Roboz: AstraZeneca: Consultancy;Janssen: Research Funding;Bristol Myers Squibb: Consultancy;Jasper Therapeutics: Consultancy;Agios: Consultancy;Novartis: Consultancy;Amgen: Consultancy;Blueprint Medicines: Consultancy;Janssen: Consultancy;Helsinn: Consultancy;Daiichi Sankyo: Consultancy;Glaxo SmithKline: Consultancy;Celgene: Consultancy;Jazz: Consultancy;MEI Pharma - IDMC Chair: Consultancy;Mesoblast: Consultancy;Actinium: Consultancy;AbbVie: Consultancy;Astex: Consultancy;Bayer: Consultancy;Astellas: Consultancy;Roche/Genentech: Consultancy;Pfizer: Consultancy;Otsuka: Consultancy. Aribi: Seagen: Consultancy. Brandwein: Astellas: Honoraria;Jazz: Honoraria;Amgen: Honoraria;Taiho: Honoraria;BMS/Celgene: Honoraria;Pfizer: Honoraria;Abbvie: Honoraria;University of Alberta: Current Employment. Döhner: Astellas: Consultancy, Honoraria, Research Funding;AstraZeneca: Consultancy, Honoraria;Berlin-Chemie: Consultancy, Honoraria;Amgen: Consultancy, Honoraria, Research Funding;Abbvie: Consultancy, Honoraria, Research Funding;Agios: Consultancy, Honoraria, Research Funding;Celgene: Consultancy, Honoraria, Research Funding;GEMoaB: Consultancy, Honoraria;Helsinn: Consultancy, Honoraria;Janssen: Consultancy, Honoraria;Jazz: Consultancy, Honoraria, Research Funding;Novartis: Consultancy, Honoraria, Research Funding;Oxford Biomedicals: Consultancy, Honoraria;Pfizer: Research Funding;Roche: Consultancy, Honoraria;Gilead: Consultancy, Honoraria;Bristol Myers Squibb: Consultancy, Honoraria, Research Funding;Astex: Consultancy, Honoraria;Ulm University Hospital: Current Employment. Fiedler: Jazz Pharmaceuticals: Consultancy, Other: support for meeting attendance;Abbvie: Consultancy, Honoraria;Morphosys: Consultancy;Celgene: Consultancy;Pfizer: Consultancy, Research Funding;Novartis: Consultancy;ARIAD/Incyte: Consultancy;Amgen: Consultancy, Other: support for meeting attendance, Patents & Royalties, Research Funding;Servier: Consultancy, Other: support for meeting attendance;Daiichi Sankyo: Consultancy, Other: support for meeting attendance;Stemline: Consultancy. Gandini: argenx: Current Employment, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months. Geddes: University of Calgary: Current Employment;Taiho: Consultancy, Membership on an entity's Board of Directors or advisory committees;Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees;Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees;Novartis: Consultancy;BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau;Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees;Amgen: Consultancy;Paladin: Consultancy;Janssen: Research Funding;Geron: Research Funding;Abbvie: Membership on an entity's Board of Directors or advisory committees, Research Funding. Hou: University of Pittsburgh Medical Center Hillman Cancer Centers: Current Employment;AbbVie: Honoraria;AstraZeneca: Honoraria;Karyopharm: Honoraria;Chinese American Hematology Oncology Network: Membership on an entity's Board of Directors or advisory committees. Howes: Janssen R&D, part of Johnson & Johnson: Current Employment;Johnson & Johnson: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Hultberg: argenx: Current Employment, Patents & Royalties. Huselton: University of Rochester: Current Employment. Jacobs: Argenx BV: Current Employment, Current equity holder in publicly-traded company;University of Antwerp: Ended employment in the past 24 months. Kane: Janssen R&D, part of Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Lech-Marańda: Takeda: Membership on an entity's Board of Directors or advisory committees;AbbVie: Membership on an entity's Board of Directors r advisory committees;Novartis: Membership on an entity's Board of Directors or advisory committees;Roche: Membership on an entity's Board of Directors or advisory committees;Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees;Amgen: Membership on an entity's Board of Directors or advisory committees;Sanofi: Membership on an entity's Board of Directors or advisory committees;Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding. Louwers: argenx: Current Employment, Patents & Royalties: Patents (no royalties). Nottage: Janssen R&D, part of Johnson & Johnson: Current Employment;Johnson & Johnson: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Platzbecker: Novartis: Honoraria;AbbVie: Honoraria;Janssen: Honoraria;Celgene/BMS: Honoraria;Geron: Honoraria;Takeda: Honoraria. Rampal: Pharmaessentia: Consultancy;BMS/Celgene: Consultancy;Abbvie: Consultancy;Sierra Oncology: Consultancy;Incyte: Consultancy, Research Funding;Blueprint: Consultancy;Disc Medicine: Consultancy;Jazz Pharmaceuticals: Consultancy;Constellation: Research Funding;Kartos: Consultancy;Stemline: Consultancy, Research Funding;CTI: Consultancy;Novartis: Consultancy;Memorial Sloan Kettering: Current Employment. Salman: Janssen: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Shah: Janssen R&D, part of Johnson & Johnson: Current Employment. Stuart: Clinical Drug Development Consultants LLC: Current Employment;Argenx: Consultancy;Cleave Therapeutics: Consultancy;Triphase Accelerator Corp: Consultancy;IgM Biosciences: Consultancy;Revolution Medicines: Consultancy;Jiya Corp:Consultancy;Geron Corp: Current holder of individual stocks in a privately-held company. Subklewe: Janssen: Consultancy;Pfizer: Consultancy, Speakers Bureau;Takeda: Speakers Bureau;Klinikum der Universität München: Current Employment;MorphoSys: Research Funding;Novartis: Consultancy, Research Funding, Speakers Bureau;Roche: Research Funding;Seattle Genetics: Consultancy, Research Funding;Miltenyi: Research Funding;Gilead: Consultancy, Research Funding, Speakers Bureau;Amgen: Consultancy, Research Funding, Speakers Bureau;BMS/Celgene: Consultancy, Research Funding, Speakers Bureau. Sumbul: argenx: Current Employment. Wang: Takeda: Consultancy, Honoraria, Other: Advisory board;Jazz Pharmaceuticals: Consultancy, Honoraria, Other: Advisory Board;Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees;Stemline Therapeutics: Consultancy, Honoraria, Other: Advisory board, Speakers Bureau;AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees;Kite Pharmaceuticals: Consultancy, Honoraria, Other: Advisory Board;GlaxoSmithKline: Consultancy, Honoraria, Other: Advisory Board;Genentech: Membership on an entity's Board of Directors or advisory committees;BMS/Celgene: Membership on an entity's Board of Directors or advisory committees;DAVA Oncology: Consultancy, Speakers Bureau;Kura Oncology: Consultancy, Honoraria, Other: Advisory board, steering committee, Speakers Bureau;Novartis: Consultancy, Honoraria, Other: Advisory Board;Mana Therapeutics: Consultancy, Honoraria;Pfizer: Consultancy, Honoraria, Other: Advisory Board, Speakers Bureau;Rafael Pharmaceuticals: Other: Data safety monitoring committee;Gilead: Consultancy, Honoraria, Other: Advisory board;Daiichi Sankyo: Consultancy, Honoraria, Other: Advisory board;PTC Therapeutics: Consultancy, Honoraria, Other: Advisory board;Genentech: Consultancy;MacroGenics: Consultancy. Wierzbowska: Jazz: Research Funding;Pfizer: Honoraria;Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees;Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees;Astellas: Honoraria, Membership on an entity's Board of Directors or advisory comm ttees;Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees;BMS: Honoraria. Yao: Statagize LLC: Current Employment;Puma Biotechnology, Inc.: Ended employment in the past 24 months;Argenx: Consultancy. Yee: Astex: Membership on an entity's Board of Directors or advisory committees, Research Funding;Janssen: Research Funding;TaiHo: Membership on an entity's Board of Directors or advisory committees;Otsuka: Membership on an entity's Board of Directors or advisory committees;Onconova: Research Funding;Pfizer: Membership on an entity's Board of Directors or advisory committees;Tolero: Research Funding;Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Paladin: Membership on an entity's Board of Directors or advisory committees;MedImmune: Research Funding;AbbVie: Honoraria;Bristol-Myers Squibb/Celgene: Membership on an entity's Board of Directors or advisory committees;Shattuck Labs: Membership on an entity's Board of Directors or advisory committees;Forma Therapeutics: Research Funding;Takeda: Membership on an entity's Board of Directors or advisory committees;Geron: Research Funding;Genentech: Research Funding;F. Hoffmann La Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding;Jazz: Research Funding. Kantarjian: Immunogen: Research Funding;Astra Zeneca: Honoraria;KAHR Medical Ltd: Honoraria;Astellas Health: Honoraria;Pfizer: Honoraria, Research Funding;NOVA Research: Honoraria;Ascentage: Research Funding;Precision Biosciences: Honoraria;Novartis: Honoraria, Research Funding;Aptitude Health: Honoraria;Ipsen Pharmaceuticals: Honoraria;Jazz: Research Funding;Daiichi-Sankyo: Research Funding;BMS: Research Funding;Amgen: Honoraria, Research Funding;AbbVie: Honoraria, Research Funding;Taiho Pharmaceutical Canada: Honoraria. Borthakur: Protagonist: Consultancy;Ryvu: Research Funding;Astex: Research Funding;GSK: Consultancy;Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees;Takeda: Membership on an entity's Board of Directors or advisory committees;University of Texas MD Anderson Cancer Center: Current Employment;ArgenX: Membership on an entity's Board of Directors or advisory committees.
ABSTRACT
Objective: During the COVID-19 pandemic, institutions turned to telehealth as the primary method of postpartum care delivery. We aimed to determine the impact of telehealth on the completion of postpartum care goals. Study Design: We compared a 14-week period, March-June 2019, before implementation of telehealth to the same calendar months post-implementation during 2020. Patients with a postpartum visit (PPV) scheduled at our institution during the study period were included. Our primary outcome was attendance to the PPV. Secondary outcomes included completion of postpartum depression (PPD) screening, contraception selection, breastfeeding status at PPV, completion of postpartum 2-hour glucose tolerance test (GTT) for women with gestational diabetes, and cardiology follow-up when recommended. Multivariable logistic regression with backward elimination was used to control for confounders. Results: Of the 1,579 patients meeting inclusion criteria, 780 were in the pre-telehealth group and 799 were in the post-telehealth group. Subjects in the post-telehealth group were 90% more likely to attend a PPV compared to those in the pre-telehealth group, even when controlling for race, prenatal care provider, parity, gestational age at delivery, and insurance status (82.9% vs. 72.4%, p < 0.001;aOR 1.90, 95% CI [1.47-2.46]). Patients in the post-telehealth group were also more likely to get screened for PPD (86.3% vs. 65.1%, p < 0.001). While subjects were as likely to choose a contraceptive method at the PPV, those in the post-telehealth group were less likely to choose long-acting reversible contraception (LARC) or permanent sterilization (26.2% vs. 33.2%, p=0.03). There was no difference in breastfeeding status at the PPV, completion rate of postpartum 2-hour GTT, or attendance to cardiology follow-up appointments between groups. Conclusion: Availability of telehealth during the COVID-19 pandemic is associated with increased PPV attendance and PPD screening. However, the availability of telehealth was also associated with a decrease in the utilization of LARC or permanent sterilization. [Formula presented]
ABSTRACT
Objective: During the COVID-19 pandemic, institutions turned to telehealth as the primary method of postpartum care delivery. We aimed to understand the patient experience around telehealth for delivery of postpartum care using a qualitative approach. Study Design: We performed individual, semi-structured patient interviews (n=25) within two weeks of a scheduled telehealth postpartum visit (PPV) at our institution. Interviews were performed by phone from 10/1/2020-1/1/2021, more than 6 months into the COVID-19 pandemic. Transcriptions were analyzed using grounded theory and coded with a systematic approach. Results: Overall, participants reported mixed preferences for the modality of the postpartum visit (in-person vs. telehealth). Those in favor of telehealth focused on its convenience and flexibility. When performed via video and audio rather than audio alone, participants felt telehealth well-simulated in-person engagement. Participants also reported similar experiences by modality regarding contraceptive planning. On the other hand, several participants raised concerns about the limitations of telehealth for physical examination, such as providing patient reassurance regarding healing after delivery. Reported facilitators to telehealth were lack of need for childcare or transportation to an in-person encounter, minimized disruption to maternal-newborn routine, and prioritizing safety during the COVID-19 pandemic. Reported barriers also included the need for childcare during the telehealth encounter, as well as difficulty finding a private space for the visit, scheduling and logistic challenges, privacy concerns, and technological difficulties. Conclusion: Telehealth is becoming an increasingly utilized modality of PPVs in the United States. In this qualitative analysis, we characterize patients’ experiences with telehealth postpartum care, and identify areas of patient concern. Future work should determine how best to provide reassurance regarding postpartum healing to further optimize telehealth for postpartum care. [Formula presented]
ABSTRACT
There is growing support to reverse mass incarceration in the United States, especially in the wake of the COVID-19 pandemic. Little is known about what types and scale of community investments are most effective to support mass decarceration. Using a public health prevention framework, we conducted a scoping review to examine community-based programs that reduced criminal legal involvement. We searched PubMed, Embase and three EBSCO databases from 1990 through September 2019 for all experimental or quasi-experimental studies testing interventions pertaining to education, housing, healthcare, employment, or social support services and how they affected an individual's criminal legal outcomes. Our review identified 53 studies that demonstrated the efficacy of early childhood educational interventions and nurse-family partnership programs, post-secondary education for incarcerated students, navigation programs linking incarcerated people to community resources, and peer support upon release to reduce criminal legal system exposure. In concert with legislative action to end mass incarceration, additional research is needed to test interventions designed to achieve mass decarceration which cross multiple domains, interrogate community-level impacts and ascertain long-term outcomes.
ABSTRACT
"Social sensors" refer to those who provide opinions through electronic communication channels such as social networks. There are two major issues in current models of sentiment analysis in social sensor networks. First, most existing models only analyzed the sentiment within the text but did not analyze the users, which led to the experimental results difficult to explain. Second, few studies extract the specific opinions of users. Only analyzing the emotional tendencies or aspect-level emotions of social users brings difficulties to the analysis of the opinion evolution in public emergencies. To resolve these issues, we propose an explainable sentiment prediction model based on the portraits of users sharing representative opinions in social sensors. Our model extracts the specific opinions of the user groups on the topics and fully considers the impacts of their diverse features on sentiment analysis. We conduct experiments on 51,853 tweets about the "COVID-19" collected from 1 May 2020 to 9 July 2020. We build users' portraits from three aspects: attribute features, interest features, and emotional features. Six machine learning algorithms are used to predict emotional tendency based on users' portraits. We analyze the influence of users' features on the sentiment. The prediction accuracy of our model is 64.88%.