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1.
PLoS One ; 19(7): e0306035, 2024.
Article in English | MEDLINE | ID: mdl-38990967

ABSTRACT

PURPOSE: The COVID-19 pandemic posed unique challenges to cancer-related care as health systems balanced competing risks of timely delivery of care and minimizing exposure to infection in a high-risk, immunocompromised patient population. This study aimed to better understand how pandemic-related factors affected the patient experience of cancer care during this time. METHODS: We conducted fifteen semi-structured interviews with adults from rural counties in Maryland who were diagnosed with and/or actively treated for cancer at the TidalHealth healthcare network between January 2020 and October 2022. RESULTS: Interviews from fifteen participants were analyzed. Two major themes emerged including COVID Impact on Care, and COVID Impact on Mental Health. Subthemes under COVID Impact on Care include Staffing Shortages, Hospital Regulations, Visitation, Importance of Advocacy, and Telehealth Utilization, and subthemes under COVID Impact on Mental Health include Loneliness, Support Networks, and Perceptions of COVID and Personal Protection. Overall, participants described positive care experiences despite notable delays, disruptions to continuity of care, difficult transitions to telemedicine, visitation policies that limited patient support, increased mental health struggles related to social distancing measures, and greater desire for patient advocacy. CONCLUSION: Our findings reveal significant impacts of the COVID-19 pandemic on experiences of cancer treatment and survivorship in a more vulnerable, rural patient population with lower healthcare access and income level. Our findings suggest areas for targeted interventions to limit disruptions to quality care in future public health emergencies.


Subject(s)
COVID-19 , Neoplasms , Qualitative Research , Telemedicine , Humans , COVID-19/epidemiology , COVID-19/psychology , Female , Male , Neoplasms/therapy , Neoplasms/psychology , Middle Aged , Aged , Adult , SARS-CoV-2 , Pandemics , Mental Health , Maryland/epidemiology , Rural Population
2.
Disaster Med Public Health Prep ; 17: e502, 2023 10 06.
Article in English | MEDLINE | ID: mdl-37800399

ABSTRACT

OBJECTIVE: Major epidemics have had a huge impact on the manufacturing industry. This study aimed to explore knowledge innovation in the field of emergency manufacturing during pandemics with a systematic quantitative analysis. METHODS: Based on the Web of Science (WOS) Core Collection, the bibliometric method and the CiteSpace tool were used. RESULTS: A total of 286 literature were obtained from the WOS database. During coronavirus disease (COVID-19), there was a surge in the number of publications. A new field of research on pandemic-triggered emergency manufacturing is gradually forming with accumulated research output. The analysis of the document co-citation showed how the research on pandemic situations and viruses brought emergency manufacturing into the research scope of scholars, and what attempts were made by the original scholars. Pandemic-triggered research hotspots and research trends in the post-pandemic era mainly boiled down to 3 aspects: technological innovation, material innovation, and management innovation in the field of emergency manufacturing. CONCLUSIONS: COVID-19 strengthened academic exchange and cooperation and promotes knowledge output in this field. This study provides an in-depth perspective for emergency manufacturing research and helps researchers realize the panorama of this field and establish future research directions.


Subject(s)
COVID-19 , Coronavirus Infections , Coronavirus , Humans , Pandemics , Bibliometrics , COVID-19/epidemiology
3.
Oncologist ; 28(9): e835-e838, 2023 09 07.
Article in English | MEDLINE | ID: mdl-37335883

ABSTRACT

Substantial gaps in national healthcare spending and disparities in cancer mortality rates are noted across counties in the US. In this cross-sectional analysis, we investigated whether differences in local county-level social vulnerability impacts cancer-related mortality. We linked county-level age-adjusted mortality rates (AAMR) from the Centers for Disease Control and Prevention (CDC) Wide-ranging Online Data for Epidemiologic Research database, to county-level Social Vulnerability Index (SVI) from the CDC Agency for Toxic Substances and Disease Registry. SVI is a metric comprising 15 social factors including socioeconomic status, household composition and disability, minority status and language, and housing type and transportation. AAMRs were compared between least and most vulnerable counties using robust linear regression models. There were 4 107 273 deaths with an overall AAMR of 173 per 100 000 individuals. Highest AAMRs were noted in older adults, men, non-Hispanic Black individuals, and rural and Southern counties. Highest mortality risk increases between least and most vulnerable counties were noted in Southern and rural counties, individuals aged 45-65, and lung and colorectal cancers, suggesting that these groups may face highest risk for health inequity. These findings inform ongoing deliberations in public health policy at the state and federal level and encourage increased investment into socially disadvantaged counties.


Subject(s)
Neoplasms , Social Vulnerability , Male , Humans , United States/epidemiology , Aged , Cross-Sectional Studies , Social Class , Longitudinal Studies
4.
bioRxiv ; 2023 Mar 14.
Article in English | MEDLINE | ID: mdl-36993642

ABSTRACT

Cas9 transgenic animals have drastically accelerated the discovery of novel immune modulators. But due to its inability to process its own CRISPR RNAs (crRNAs), simultaneous multiplexed gene perturbations using Cas9 remains limited, especially by pseudoviral vectors. Cas12a/Cpf1, however, can process concatenated crRNA arrays for this purpose. Here, we created conditional and constitutive LbCas12a knock-in transgenic mice. With these mice, we demonstrated efficient multiplexed gene editing and surface protein knockdown within individual primary immune cells. We showed genome editing across multiple types of primary immune cells including CD4 and CD8 T cells, B cells, and bone-marrow derived dendritic cells. These transgenic animals, along with the accompanying viral vectors, together provide a versatile toolkit for a broad range of ex vivo and in vivo gene editing applications, including fundamental immunological discovery and immune gene engineering.

5.
Cancers (Basel) ; 14(21)2022 Oct 30.
Article in English | MEDLINE | ID: mdl-36358766

ABSTRACT

BACKGROUND: Fibrolamellar hepatocellular carcinoma (FLC) is a rare form of liver cancer primarily affecting children and young adults. Although considered a subset of hepatocellular carcinoma (HCC), FLC has unique molecular and pathologic characteristics, suggesting that it may require different treatment. Immune checkpoint inhibitors (ICIs) are used in the treatment of HCC, but efficacy and safety in FLC has not been characterized. METHODS: We performed a multicenter retrospective analysis of patients with FLC to determine responses to ICI therapy. Response rates were assessed based on RECIST 1.1 criteria, and Kaplan-Meier statistics were used for progression-free survival (PFS) and overall survival (OS). RESULTS: FLC tumors were characterized by low tumor mutational burden (TMB) and absent PD-L1 expression. We identified 19 patients who received ICIs, including 15 who received ICI therapy alone [programmed death receptor 1 (PD-1) inhibitor, +/- cytotoxic T lymphocyte antigen-4 (CTLA-4) inhibitor]. Objective tumor responses were observed in 3/19 patients (15.8%), including 2/15 patients (13.3%) who received ICIs alone, all partial responses. Median PFS and OS were 5.5 and 26.0 months, respectively. Grade 3-4 immune related adverse events were observed in 4/19 (21.1%) patients. CONCLUSIONS: ICI therapy has modest clinical activity in FLC, and novel therapeutic combinations are needed.

6.
JAMA Pediatr ; 176(12): 1265-1266, 2022 12 01.
Article in English | MEDLINE | ID: mdl-36215054

ABSTRACT

This cohort study examines trends from 2008 to 2019 in dispensations of controlled medications to US adolescents and young adults.


Subject(s)
Biopharmaceutics , Adolescent , Humans , Young Adult
7.
Clin Trials ; 19(4): 442-451, 2022 08.
Article in English | MEDLINE | ID: mdl-35482320

ABSTRACT

BACKGROUND: Adverse events identified during clinical trials can be important early indicators of drug safety, but complete and timely data on safety results have historically been difficult to access. The aim was to compare the availability, completeness, and concordance of safety results reported in ClinicalTrials.gov and peer-reviewed publications. METHODS: We analyzed clinical trials used in the Food and Drug Administration safety assessment of new drugs approved between 1 July 2018 and 30 June 2019. The key safety outcomes examined were all-cause mortality, serious adverse events, adverse events, and withdrawals due to adverse events. Availability of safety results was measured by the presence and timing of a record of trial-level results in ClinicalTrials.gov and a corresponding peer-reviewed publication. For the subset of trials with available results, completeness was defined as the reporting of safety results for all participants and compared between ClinicalTrials.gov and publications. To assess concordance, we compared the numeric results for safety outcomes reported in ClinicalTrials.gov and publications to results in Food and Drug Administration trial reports. RESULTS: Among 156 trials studying 52 drugs, 91 (58.3%) trials reported safety results in ClinicalTrials.gov and 106 (67.9%) in peer-reviewed publications (risk difference = -9.6%, 95% confidence interval = -20.3 to 1.0). All-cause mortality was reported sooner in published articles compared with ClinicalTrials.gov (log-rank test, p = 0.01). There was no difference in time to reporting for serious adverse events (p = 0.05), adverse events (p = 0.09), or withdrawals due to adverse events (p = 0.20). Complete reporting of all-cause mortality was similar in ClinicalTrials.gov and publications (74.7% vs 78.3%, respectively; risk difference = -3.6%, 95% confidence interval = -15.5 to 8.3) and higher in ClinicalTrials.gov for serious adverse events (100% vs 79.2%; risk difference = 20.8%, 95% confidence interval = 13.0 to 28.5) and adverse events (100% vs 86.8%; risk difference = 13.2%, 95% confidence interval = 6.8 to 19.7). Withdrawals due to adverse events were less often completely reported in ClinicalTrials.gov (62.6% vs 92.5%; risk difference = -29.8%, 95% confidence interval = -40.1 to -18.7). No difference was found in concordance of results between ClinicalTrials.gov and publications for all-cause mortality, serious adverse events, or withdrawals due to adverse events. CONCLUSION: Safety results were available in ClinicalTrials.gov at a similar rate as in peer-reviewed publications, with more complete reporting of certain safety outcomes in ClinicalTrials.gov. Future efforts should consider adverse event reporting in ClinicalTrials.gov as an accessible data source for post-marketing surveillance and other evidence synthesis tasks.


Subject(s)
United States Food and Drug Administration , Cross-Sectional Studies , Humans , Pharmaceutical Preparations , United States
8.
Cell ; 178(5): 1189-1204.e23, 2019 08 22.
Article in English | MEDLINE | ID: mdl-31442407

ABSTRACT

CD8 T cells play essential roles in anti-tumor immune responses. Here, we performed genome-scale CRISPR screens in CD8 T cells directly under cancer immunotherapy settings and identified regulators of tumor infiltration and degranulation. The in vivo screen robustly re-identified canonical immunotherapy targets such as PD-1 and Tim-3, along with genes that have not been characterized in T cells. The infiltration and degranulation screens converged on an RNA helicase Dhx37. Dhx37 knockout enhanced the efficacy of antigen-specific CD8 T cells against triple-negative breast cancer in vivo. Immunological characterization in mouse and human CD8 T cells revealed that DHX37 suppresses effector functions, cytokine production, and T cell activation. Transcriptomic profiling and biochemical interrogation revealed a role for DHX37 in modulating NF-κB. These data demonstrate high-throughput in vivo genetic screens for immunotherapy target discovery and establishes DHX37 as a functional regulator of CD8 T cells.


Subject(s)
CD8-Positive T-Lymphocytes/metabolism , RNA Helicases/genetics , Animals , Breast Neoplasms/pathology , Breast Neoplasms/therapy , CD8-Positive T-Lymphocytes/cytology , CD8-Positive T-Lymphocytes/immunology , Cell Line, Tumor , Clustered Regularly Interspaced Short Palindromic Repeats/genetics , Cytokines/genetics , Cytokines/metabolism , Female , Humans , Immunologic Memory , Immunotherapy , Male , Mice , Mice, Knockout , NF-kappa B/metabolism , Programmed Cell Death 1 Receptor/metabolism , RNA Helicases/deficiency , RNA, Guide, Kinetoplastida/metabolism , Transcriptome
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