Immune-Related Adverse Events of Immune Checkpoint Inhibitors: Incidence, Risk Factors, Clinical Outcomes, and Economic Burden in Older Adults with Non-Small Cell Lung Cancer

To fill the gap in existing literature related to immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC), this dissertation focused on: 1) assessing the incidence, spectrum and risk factors for the development of irAEs; 2) assessing the clinical impact of irAE occurrence on survival and treatment discontinuation; 3) analyzing and estimating the incremental economic burden of irAEs among an older population in the United States (US). A retrospective cohort study was conducted using the SEER-Medicare 2020 linkage database in order to evaluate the three study objectives. The dissertation included 8,175 patients diagnosed with NSCLC aged 65 years or older who received one or more PD-1/PD-L1 inhibitor doses between March 1st 2015 and December 31st 2018. As a starting point, this study found that nearly half of older NSCLC patients experienced irAEs post-ICI treatment. In most cases, the first irAE occurs within six months of starting therapy, but it can occur for up to 12 months. The earliest onset of irAEs was hematological, followed by central nervous system, cardiac, pulmonary, renal, endocrine, and liver events. IrAEs affecting the GI system, the skin, and the musculoskeletal system occurred relatively late. Pneumonitis, hypothyroidism, arrhythmia, and acute kidney injury (AKI) were the most common IrAEs. IrAE incidence was higher among patients living in the Midwest and Northeast regions of the US, with lower socioeconomic status, undergoing certain ICI treatments, and having specific health conditions. Furthermore, this study suggests that irAEs are associated with an increased risk of death and ICI discontinuation. There is a correlation between worse outcomes in patients with pneumonitis, arrhythmia, AKI, hepatitis, and colitis. Patients with hypothyroidism and skin-related irAEs, however, were more likely to live longer and receive longer treatment durations. Finally, this study demonstrated that occurrence of irAEs led to higher healthcare resource utilization (HCRU) and costs (estimated incremental cost: $21804.50). Most of the cost increase was attributed to hospitalizations, followed by visits to offices and skilled nursing facilities. There was a substantial increase in costs associated with managing the specific irAEs, which ranged from$1,765.91 to $8,975.99 per month. IrAEs with the highest costs include pneumonia, arrhythmia, AKI, and hepatitis. An extensive analysis of the characteristics, risk factors, and clinical and economic impact of irAEs in older NSCLC patients was conducted in this study. The findings of this study can be used by patients, clinicians, and payers to provide guidance on treatment options, to predict and prevent irAEs during immunotherapy, and to weigh the relative risk and benefit of ICIs for older adults with NSCLC

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Information model of coal mine safety production monitoring system based on OPC UA

There are many kinds of subsystems in the coal mine safety production monitoring system, and the types of equipments in the subsystems are multifarious, which leads to the low semantic completeness of data and the fragmentation of information interaction data caused by the heterogeneous information of equipment. At present, although the research of coal mine informatization construction has basically realized the network integration of each subsystem, the massive data obtained can not be effectively shared, and the integration analysis can not be carried out. In order to solve the above problems, this paper proposes an information model of coal mine safety production monitoring system based on OPC UA. According to the relevant information of coal mine safety production monitoring system and the general modeling rules of OPC UA information model, the mapping relationship between actual equipment of coal mine safety production monitoring system and information model is analyzed, and the overall structure of information model of coal mine safety production monitoring system is proposed. It is pointed out that when new functions need to be extended in coal mine safety production monitoring system, they can be extended in function set. When new equipment needs to be added to the subsystem, new components can be added to the equipment set to ensure the extensibility of the information model. Taking the information model of gas extraction monitoring system as an example, the information model of methane sensor is established by using UaModeler tool. After the information model is graphically designed, the XML description file is generated and imported into the address space of OPC UA server. Through the third-party client UaExpert connecting server to test the information model of the OPC UA, the results show that the information model can realize the mapping in the address space of the OPC UA according to the mapping rules, and access the server's address space through the OPC UA client. The attributes of any object in each coal mine safety production monitoring subsystems can be obtained, which verifies the feasibility of using the OPC UA information model to realize the information interconnection

Transcribing Natural Languages for the Deaf via Neural Editing Programs

This work studies the task of glossification, of which the aim is to em transcribe natural spoken language sentences for the Deaf (hard-of-hearing) community to ordered sign language glosses. Previous sequence-to-sequence language models trained with paired sentence-gloss data often fail to capture the rich connections between the two distinct languages, leading to unsatisfactory transcriptions. We observe that despite different grammars, glosses effectively simplify sentences for the ease of deaf communication, while sharing a large portion of vocabulary with sentences. This has motivated us to implement glossification by executing a collection of editing actions, e.g. word addition, deletion, and copying, called editing programs, on their natural spoken language counterparts. Specifically, we design a new neural agent that learns to synthesize and execute editing programs, conditioned on sentence contexts and partial editing results. The agent is trained to imitate minimal editing programs, while exploring more widely the program space via policy gradients to optimize sequence-wise transcription quality. Results show that our approach outperforms previous glossification models by a large margin, improving the BLEU-4 score from 16.45 to 18.89 on RWTH-PHOENIX-WEATHER-2014T and from 18.38 to 21.30 on CSL-Daily

Incidence and risk factors of immune‐related adverse events induced by immune checkpoint inhibitors among older adults with non‐small cell lung cancer

Abstract Background Immune checkpoint inhibitor (ICI) treatment has been linked to a variety of immune‐related adverse events (irAEs), which can affect any organ system. The incidence and risk factors of irAEs have not been adequately evaluated among older adults with NSCLC. Methods A cohort study was conducted using 1999–2019 SEER‐Medicare data among beneficiaries aged ≥65 years with a diagnosis of NSCLC who received nivolumab, pembrolizumab, or atezolizumab. Incident irAEs were identified post‐ICI initiation. Demographic, cancer‐related characteristics, and clinical history risk factors of irAEs were evaluated with competing events considered. Results A total of 8175 older NSCLC patients were included (with 46.8% experiencing irAEs). Pneumonitis (16.5%), hypothyroidism (10.5%), arrhythmia (11.18%), and acute kidney injury (AKI) (5.8%) were the most common irAEs. The median time to first irAE was 82 days (IQR: 29–182 days). The earliest onset of irAE occurrence was for hematologic irAEs, while the latest were gastrointestinal, dermatologic, and musculoskeletal irAEs. Fine–Gray regression modeling revealed significantly greater hazards of irAE occurrence in patients who received pembrolizumab at index, did not have CNS metastases, had a history of autoimmune disorder, and had chemotherapy in combination with ICI. Race, socioeconomic status, previous radiation therapy, and comorbidity burden were found to be associated with the occurrence of certain type of irAEs. Conclusion A significant proportion of older patients with NSCLC develop an irAE after receiving ICI treatment. Factors related to cancer and treatment as well as demographics contribute to the increased risk of irAEs. Close monitoring and prediction of irAE among older patients receiving ICI is warranted

Association of antecedent statin use on 30-day, 60-day and 90-day mortality among Mississippi Medicaid beneficiaries diagnosed with COVID-19

Objective To assess if the antecedent statin use was associated with all-cause death among COVID-19 patients enrolled in Medicaid.Design Cohort study.Setting Mississippi Medicaid population.Participants This study included 10 792 Mississippi Medicaid-enrolled patients between 18 and 64 years of age with a confirmed COVID-19 diagnosis from March 2020 to June 2021.Intervention Antecedent statin use, which was determined by a record of statin prescription in the 90-day period prior to the COVID diagnosis.Main outcome measures The outcomes of interest included mortality from all cause within 30 days, 60 days and 90 days after index.Results A total of 10 792 patients with COVID-19 met the inclusion and exclusion criteria, with 13.1% of them being antecedent statin users. Statin users were matched 1:1 with non-users based on age, sex, race, comorbidities and medication use by propensity score matching. In total, the matched cohort consisted of 1107 beneficiaries in each group. Multivariable logistic regression showed that statin users were less likely to die within 30 days (adjusted OR: 0.51, 95% CI: 0.32 to 0.83), 60 days (OR: 0.56, 95% CI: 0.37 to 0.85) and 90 days (OR: 0.55, 95% CI: 0.37 to 0.82) after diagnosis of COVID-19. Those with low-intensity/moderate-intensity statin use had significantly lower mortality risk in the 60-day and the 90-day follow-up period, while the high intensity of statin use was only found to be significantly associated with a lower odd of mortality within 30 days post index.Conclusion After COVID infection, Medicaid beneficiaries who had taken statins antecedently could be at lower risk for death. For patients with chronic conditions, continuity of care is crucial when interruptions occur in their medical care. Further research is required to further investigate the potential mechanisms and optimal use of statins in COVID-19 treatment

Publication trends of research on diabetes mellitus and T cells (1997–2016): A 20-year bibliometric study

<div><p>Introduction</p><p>Diabetes Mellitus (DM) is a huge burden for human health. Recent studies show the close relationship between DM and T cells. We investigated the trend in DM and T cells research.</p><p>Methods</p><p>Using the Web of Science database, we searched the publications on DM and T cells in 1997–2016, and studied the source data using bibliometric methodology. Excel 2016, GraphPad Prism 5, and VOSviewer software were used to analyze the publication trend in DM and T cells research.</p><p>Results</p><p>We found a total of 1077 publications with 38109 citations up to January 23, 2017. The highest contribution came from the United States, with 48.38% of the publications, 61.44% of the citations and the highest H-index (74). China had the 5th place for total publications, but ranked 11th both for citation frequency (604) and H-index (13). The inflection point of the global DM and T cells publications was in 2000. Journal of Immunology published the most related articles (164). Santamaria P. was the leading scholar in this field with the most publications (35). The keywords “regulatory T cell” and “autoimmune diabetes” were mentioned more than 300 times. Furthermore, type 2 (T2)DM, T cell immunoglobulin and mucin domain (TIM) and obesity are becoming popular research topics in this field.</p><p>Conclusion</p><p>The quantity of publications on DM and T cells grew rapidly around year 2000, but has relatively decreased recently. The United States had the leading position in global research. There was a discrepancy between productivity and quality of publications from China. Latest progress is most likely first published by the Journal of Immunology. Santamaria P., Roep B.O. and Peakman M. were the pioneer scholars in this field. Most researchers have focused on “regulatory T cell” and “autoimmune diabetes” research. In future, T2DM, TIM and obesity may be the popular areas.</p></div

The logistic model fitting curves of growth trends of DM and T cells publications.

<p>(A) Global; (B)United States; (C)Canada; (D)China.</p

Top 10 authors with the most publications related to DM and T cells research.

<p>Top 10 authors with the most publications related to DM and T cells research.</p