Feature Gradient Flow for Interpreting Deep Neural Networks in Head and Neck Cancer Prediction

This paper introduces feature gradient flow, a new technique for interpreting deep learning models in terms of features that are understandable to humans. The gradient flow of a model locally defines nonlinear coordinates in the input data space representing the information the model is using to make its decisions. Our idea is to measure the agreement of interpretable features with the gradient flow of a model. To then evaluate the importance of a particular feature to the model, we compare that feature's gradient flow measure versus that of a baseline noise feature. We then develop a technique for training neural networks to be more interpretable by adding a regularization term to the loss function that encourages the model gradients to align with those of chosen interpretable features. We test our method in a convolutional neural network prediction of distant metastasis of head and neck cancer from a computed tomography dataset from the Cancer Imaging Archive

Comparative Cardiovascular Risk of Abatacept and Tumor Necrosis Factor Inhibitors in Patients With Rheumatoid Arthritis With and Without Diabetes Mellitus: A Multidatabase Cohort Study

Background: We examined the cardiovascular risk of abatacept compared with tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis with and without diabetes mellitus (DM). Methods and Results: We conducted a cohort study of patients with rheumatoid arthritis who newly started abatacept or TNF inhibitors using claims data from Medicare and MarketScan. The primary outcome was a composite cardiovascular end point of myocardial infarction (MI), stroke/transient ischemic attack, and coronary revascularization. To account for >60 baseline characteristics, abatacept initiators were 1:1 propensity score (PS) matched to TNF initiators in each database. Cox proportional hazards models estimated hazard ratio (HR) and 95% confidence interval (CI) in the PS‐matched cohort per database. A fixed‐effects meta‐analysis pooled database‐specific HRs. We included a total of 13 039 PS‐matched pairs of abatacept and TNF inhibitor initiators (6103 pairs in Medicare and 6936 pairs in MarketScan). A total of 34.7% in Medicare and 19.8% in MarketScan had baseline DM. The HR (95% CI) for the primary outcome associated with abatacept use versus TNF inhibitor was 0.81 (0.66–0.99) in Medicare and 0.95 (0.74–1.23) in MarketScan, with a pooled HR of 0.86 (95% CI, 0.73–1.01; P=0.3 for heterogeneity). The risk of the primary outcome was lower in abatacept initiators versus TNF inhibitors in the DM subgroup, with a pooled HR of 0.74 (95% CI, 0.57–0.96; P=0.7 for heterogeneity), but not in the non‐DM subgroup, with a pooled HR of 0.94 (95% CI, 0.77–1.14; P=0.4 for heterogeneity). Conclusions: In this large population‐based cohort of patients with rheumatoid arthritis, abatacept use appeared to be associated with a modestly reduced cardiovascular risk when compared with TNF inhibitor use, particularly in patients with DM

Conformally Anodizing Hierarchical Structure in a Deformed Tube towards Energy-saving Liquid Transportation

The creation of drag-reducing surfaces in deformed tubes is of vital importance to thermal management, energy, and environmental applications. However, it remains a great challenge to tailor the surface structure and wettability inside the deformed tubes of slim and complicated feature. Here, we describe an electrochemical anodization strategy to achieve uniform and superhydrophobic coating of TiO2 nanotube arrays throughout the inner surface in deformed/bend titanium tubes. Guided by a hybrid carbon fibre cathode, conformal electric field can be generated to adaptatively fit the complex geometries in the deformed tube, where the structural design with rigid insulating beads can self-stabilize the hybrid cathode at the coaxial position of the tube with the electrolyte flow. As a result, we obtain a superhydrophobic coating with a water contact angle of 157° and contact angle hysteresis of less than 10°. Substantial drag reduction can be realised with an overall reduction up to 25.8 % for the anodized U-shaped tube. Furthermore, we demonstrate to spatially coat tubes with complex geometries, to achieve energy-saving liquid transportation. This facile coating strategy has great implications in liquid transport processes with the user-friendly approach to engineer surface regardless of the deformation of tube/pipe

Risk of Non-Vertebral Fracture in Gout Compared to Rheumatoid Arthritis

Objective: To evaluate the risk of non-vertebral fractures in patients with gout compared with those with rheumatoid arthritis (RA). Methods: Using claims data from Medicare (2008–2015), we conducted a cohort study of patients with gout versus RA matched on age, sex, and index date with a 1:1 ratio. The primary outcome was a composite endpoint of non-vertebral fractures including hip, pelvis, humerus, and wrist identified with the validated algorithms. We also assessed hip fractures separately. Multivariable Cox proportional hazards regression estimated the hazard ratio (HR) for the outcomes in gout versus RA adjusted for 45 covariates. Results: We included a total of 134,157 matched pairs of gout and RA patients (mean age: 73.7 years). Risk factors for fracture were more prevalent in RA, while other comorbidities including obesity, coronary heart disease, hypertension, and diabetes were more common in gout. Over the mean 2.8 years follow-up, the incidence rate (IR)/1000 person-year (PY) of non-vertebral fractures was 10.42 in gout and 15.01 in RA. For hip fractures, the IR/1000 PY was 4.86 in gout and 7.73 in RA. The multivariable HR associated with gout versus RA was 0.84 (95% confidence interval (CI) 0.80–0.88) for non-vertebral fractures and 0.76 (95% CI 0.71–0.82) for hip fractures. Stratified analyses by age, sex, prior fractures, steroid use, and TNF inhibitor use showed similar results. Conclusions: In this large cohort of older patients, gout was associated with a modestly decreased risk of non-vertebral or hip fractures versus RA. However, non-vertebral fractures occurred frequently in both gout and RA

Real‐World Treatment Effectiveness of Disease‐Modifying Antirheumatic Drugs by Serostatus Among Patients With Rheumatoid Arthritis

Objective The objective of this study was to compare the clinical effectiveness of biologic disease‐modifying antirheumatic drugs (bDMARDs) or Janus kinase inhibitors (JAKi) among seropositive versus seronegative patients with rheumatoid arthritis (RA) in a real‐world setting. Methods We used Optum's deidentified Clinformatics Data Mart Database (January 1, 2004, to March 31, 2021) linked with outpatient laboratory test results. The study population was adult patients with RA who initiated a bDMARD or JAKi. The index date was the dispensing of the first‐ever study drug. At least 1‐year continuous enrollment before and after the index date was required. Disenrollment due to death after the index date was allowed. Serostatus was defined using laboratory test results or the International Classification of Diseases, 10th Revision code M05x or M06.0x any time prior to the index date. Treatment effectiveness was measured based on a claims‐based composite endpoint at 1‐year post index, including nonoccurrence of any of the following: addition of conventional synthetic DMARDs, addition of or switching to new bDMARDs/JAKi, initiation of glucocorticoids, increased glucocorticoid dose, or death. Log‐binomial regression models were constructed to estimate the risk ratio (RR) with 95% confidence interval (CI) comparing seropositive patients with seronegative patients, adjusting for more than 60 baseline covariates. Results We identified a total of 7813 seropositive patients and 4202 seronegative patients. The mean (±SD) age was 56.7 (±14.0) years; 77.9% were female. The risk of 1‐year treatment effectiveness was 70.2% among seropositive patients and 69.8% among seronegative patients. The adjusted RR (95% CI) was 1.00 (0.98‐1.02). Conclusion In this real‐world cohort study, seropositive and seronegative patients with RA had similar 1‐year treatment effectiveness after initiating a bDMARD/JAKi

Reversible conversion-alloying of Sb2O3 as a high-capacity, high-rate, and durable anode for sodium ion batteries

Sodium ion batteries are attracting ever-increasing attention for the applications in large/grid scale energy storage systems. However, the research on novel Na-storage electrode materials is still in its infancy, and the cycling stability, specific capacity, and rate capability of the reported electrode materials cannot satisfy the demands of practical applications. Herein, a high performance Sb2O3 anode electrochemically reacted via the reversible conversion-alloying mechanism is demonstrated for the first time. The Sb2O3 anode exhibits a high capacity of 550 mAh g-1 at 0.05 A g-1 and 265 mAh g-1 at 5 A g-1. A reversible capacity of 414 mAh g-1 at 0.5 A g-1 is achieved after 200 stable cycles. The synergistic effect involving conversion and alloying reactions promotes stabilizing the structure of the active material and accelerating the kinetics of the reaction. The mechanism may offer a well-balanced approach for sodium storage to create high capacity and cycle-stable anode materials

Spatially-confined lithiation-delithiation in highly dense nanocomposite anodes towards advanced lithium-ion batteries

Spatially-confined electrochemical reactions are firstly realized in a highly dense nanocomposite anode for high performance lithium ion batteries. The spatially-confined lithiation-delithiation effectively avoids inter-cluster migration and perfectly retains full structural integrity. Large reversible capacity, high rate capability and superior cycling stability are achieved simultaneously. This spatially-confined lithiation-delithiation offers novel insight to enhance cycling performance of high capacity anode materials

Factors associated with initial or subsequent choice of biologic disease-modifying antirheumatic drugs for treatment of rheumatoid arthritis

Abstract Background Biologic disease-modifying antirheumatic drugs (DMARDs) are increasingly used for rheumatoid arthritis (RA) treatment. However, little is known based on contemporary data about the factors associated with DMARDs and patterns of use of biologic DMARDs for initial and subsequent RA treatment. Methods We conducted an observational cohort study using claims data from a commercial health plan (2004–2013) and Medicaid (2000–2010) in three study groups: patients with early untreated RA who were naïve to any type of DMARD and patients with prevalent RA with or without prior exposure to one biologic DMARD. Multivariable logistic regression models were used to examine the effect of patient demographics, clinical characteristics and healthcare utilization factors on the initial and subsequent choice of biologic DMARDs for RA. Results We identified a total of 195,433 RA patients including 78,667 (40%) with early untreated RA and 93,534 (48%) and 23,232 (12%) with prevalent RA, without or with prior biologic DMARD treatment, respectively. Patients in the commercial insurance were 87% more likely to initiate a biologic DMARD versus patients in Medicaid (OR = 1.87, 95% CI = 1.70–2.05). In Medicaid, African-Americans had lower odds of initiating (OR = 0.59, 95% CI = 0.51–0.68 in early untreated RA; OR = 0.71, 95% CI = 0.61–0.74 in prevalent RA) and switching (OR = 0.71, 95% CI = 0.55–0.90) biologic DMARDs than non-Hispanic whites. Prior use of steroid and non-biologic DMARDs predicted both biologic DMARD initiation and subsequent switching. Etanercept, adalimumab, and infliximab were the most commonly used first-line and second-line biologic DMARDS; patients on anakinra and golimumab were most likely to be switched to other biologic DMARDS. Conclusions Insurance type, race, and previous use of steroids and non-biologic DMARDs were strongly associated with initial or subsequent treatment with biologic DMARDs

Real-world patient characteristics and use of disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis: a cross-national study

Introduction: Rheumatoid arthritis (RA) is associated with significant morbidity and economic burden. This study aimed to compare baseline characteristics and patterns of anti-inflammatory drug use and disease-modifying anti-rheumatic drug (DMARD) use among patients with RA in Southern Italy versus the United States. Method: Using Caserta Local Health Unit (Italy) and Optum’s de-identified Clinformatics® Data Mart (United States) claims databases, patients with ≥ 2 diagnosis codes for RA during the study period (Caserta: 2010–2018; Optum: 2010–2019) were identified. Baseline patient characteristics, as well as proportion of RA patients untreated/treated with NSAIDs/glucocorticoids/conventional DMARDs (csDMARDs)/biological/targeted synthetic DMARDs (b/tsDMARDs) during the first year of follow-up, and the proportion of RA patients with ≥ 1 switch/add-on between the first and the second year of follow-up, were calculated. These analyses were then stratified by age group (< 65; ≥ 65). Results: A total of 9227 RA patients from Caserta and 195,951 from Optum databases were identified (two-thirds were females). During the first year of follow-up, 45.9% RA patients from Optum versus 79.9% from Caserta were exclusively treated with NSAIDs/glucocorticoids; 17.2% versus 11.3% from Optum and Caserta, respectively, were treated with csDMARDs, mostly methotrexate or hydroxychloroquine in both cohorts. Compared to 0.6% of RA patients from Caserta, 3.2% of the Optum cohort received ≥ 1 b/tsDMARD dispensing. Moreover, 61,655 (33.7%) patients from Optum cohort remained untreated compared to 748 (8.3%) patients from the Caserta cohort. The subgroup analyses stratified by age showed that 42,989 (39.8%) of elderly RA patients were untreated compared to 18,666 (24.9%) young adult RA patients in Optum during the first year of follow-up. Moreover, a higher proportion of young adult RA patients was treated with b/tsDMARDs, with and without csDMARDs, compared to elderly RA patients (Optum<65: 6.4%; Optum≥65: 1.0%; P-value < 0.001; Caserta<65: 0.8%; Caserta≥65: 0.1%; P-value < 0.001). Among RA patients untreated during the first year after ID, 41.2% and 48.4% RA patients from Caserta and Optum, respectively, received NSAIDs, glucocorticoids, and cs/b/tsDMARDs within the second year of follow-up. Stratifying the analysis by age groups, 50.6% of untreated young RA patients received study drug dispensing within the second year of follow-up, compared to only 36.7% of elderly RA patients in Optum. Interestingly, more young adult RA patients treated with csDMARDs during the first year after ID received a therapy escalation to b/tsDMARD within the second year after ID in both cohorts, compared to elderly RA patients (Optum<65: 7.8%; Optum≥65: 1.8%; Caserta<65: 3.2%; Caserta≥65: 0.6%). Conclusions: Most of RA patients, with heterogeneous baseline characteristics in Optum and Caserta cohorts, were treated with anti-inflammatory/csDMARDs rather than bDMARDs/tsDMARDs during the first year post-diagnosis, especially in elderly RA patients, suggesting a need for better understanding and dealing with barriers in the use of these agents for RA patients. • Substantial heterogeneity in baseline characteristics and access to bDMARD or tsDMARD drugs between RA patients from the United States and Italy exists.• Most of RA patients seem to be treated with anti-inflammatory/csDMARD drugs rather than bDMARD/tsDMARD drugs during the first year post-diagnosis.• RA treatment escalation is less frequent in old RA patients than in young adult RA patients.• An appropriate use of DMARDs should be considered to achieve RA disease remission or low disease activity