Thromboembolic risk in patients with lung cancer receiving systemic therapy.

In this retrospective study, we investigated the influence of chemotherapy and immunotherapy on thromboembolic risk among United States Veterans with lung cancer during their first 6 months (180 days) following initiation of systemic therapy. Included patients received treatment with common front-line agents that were divided into four groups: chemotherapy alone, immunotherapy alone, combination of chemo- and immunotherapies, and molecularly targeted therapies (control group). The cohort experienced a 7·4% overall incidence of thrombosis, but the analysis demonstrated significantly different rates among the different groups. We explored models incorporating multiple confounding variables as well as the competing risk of death, and these results indicated that both chemo- and immunotherapies were associated with an increased incidence of thrombosis, either alone or combined, compared with the control group (7·56%, P = 2.2 × 10-16 ; 10·2%, P = 2.2 × 10-16 ; and 7·87%, P = 2.4 × 10-14 respectively vs. 4·10%). The Khorana score was found to be associated with increased risk, as were vascular disease and metastases. We found an association between risk of thrombosis and the use of anticoagulation, accounting for several confounders, including history of thrombosis. Further study is warranted to better determine the drivers of thromboembolic risk and to identify ways to mitigate this risk for patients.

Survival Among Veterans Receiving Steroids for Immune-Related Adverse Events After Immune Checkpoint Inhibitor Therapy.

Importance: Systemic steroids are commonly used to manage immune-related adverse events (irAEs), but it remains unclear whether they may undermine immune checkpoint inhibitor (ICI) therapy outcomes. Few studies have assessed the impact of steroid timing and its association with continuation or cessation of ICI therapy. Objective: To characterize how systemic steroids and steroid timing for irAEs are associated with survival in patients receiving ICI therapy. Design, Setting, and Participants: This multicenter retrospective cohort study encompassed veterans receiving ICI for cancer between January 1, 2010, and December 31, 2021. Data analysis was conducted September 8, 2023. Exposures: Identifiable primary diagnosis of cancer. Patients were categorized into 3 cohorts: those receiving no steroids, systemic steroids for irAEs, and steroids for non-irAE-associated reasons. All eligible patients received 1 or more doses of an ICI (atezolizumab, avelumab, cemiplimab, durvalumab, ipilimumab, nivolumab, or pembrolizumab). Eligible patients in the steroid group received at least 1 dose (intravenous, intramuscular, or oral) of dexamethasone, hydrocortisone, methylprednisolone, prednisone, or prednisolone. Steroid use at baseline for palliation or infusion prophylaxis or delivered as a single dose was deemed to be non-irAE associated. All other patterns of steroid use were assumed to be for irAEs. Main Outcomes and Measures: The primary outcome was overall survival, with a 5-year follow-up after ICI initiation. Kaplan-Meier survival analyses were performed with pairwise log-rank tests to determine significance. Risk was modeled with Cox proportional hazard regression. Results: The cohort consisted of 20 163 veterans receiving ICI therapy including 12 221 patients (mean [SD] age, 69.5 [8.0] years; 11 830 male patients [96.8%]; 9394 White patients [76.9%]) who received systemic steroids during ICI treatment and 7942 patients (mean [SD] age, 70.3 [8.5] years; 7747 male patients [97.5%]; 6085 White patients [76.6%]) who did not. Patients with an irAE diagnosis had significantly improved overall survival (OS) compared with those without (median [IQR] OS, 17.4 [6.6 to 48.5] months vs 10.5 [3.5 to 36.8] months; adjusted hazard ratio, 0.84; 95% CI, 0.81-0.84; P < .001). For patients with irAEs, systemic steroids for irAEs were associated with significantly improved survival compared with those who received steroids for non-irAE-related reasons or no steroid treatment (median [IQR] OS, 21.3 [9.3 to 58.2] months vs 13.6 [5.5 to 33.7] months vs 15.8 [4.9 to not reached] months; P <.001). However, among those who received steroids for irAEs, early steroid use (<2 months after ICI initiation) was associated with reduced relative survival benefit vs later steroid use, regardless of ICI continuation or cessation following steroid initiation (median [IQR] OS after ICI cessation 4.4 [1.9 to 19.5] months vs 16.0 [8.0 to 42.2] months; median [IQR] OS after ICI continuation, 16.0 [7.1 to not reached] months vs 29.2 [16.5 to 53.5] months; P <.001). Conclusions and Relevance: This study suggests that steroids for irAE management may not abrogate irAE-associated survival benefits. However, early steroid administration within 2 months of ICI initiation is associated with shorter survival despite continuation of ICI therapy.

Statin use is associated with improved overall survival in patients with melanoma.

Melanoma remains a leading cause of cancer morbidity and mortality. Recent literature suggests that statin use may improve outcomes in patients with cancer. In order to determine whether statins may improve survival in melanoma patients, we analyzed data from the Veterans Health Administration Corporate Data Warehouse that contains individually identifiable clinical and demographic information from the 1990s to the present for over 19 million individual veterans. We found that melanoma patients who were taking a statin had better 5-year OS when compared with veterans not taking statins. This relationship remained significant in a multivariate model (hazard ratio, 0.38; 95% confidence interval, 0.34-0.43 for statin user vs. nonuser). Importantly, this effect was much larger than the effect of statins in the general population and was remained after controlling for the use of other medications (beta-blocker), implying that statins may have a direct effect on survival in melanoma patients.

Mortality and Conversion to Transfemoral Amputation After Transtibial Amputation in the Veterans Affairs Health System.

INTRODUCTION: Transtibial below-knee amputation (BKA) is associated with considerable morbidity, particularly in the vasculopathic population. The purpose of this study was to determine the cumulative probability of undergoing transfemoral above-knee amputation (AKA) conversion within 5 years of BKA and associated risk factors while accounting for the competing risk of death. METHODS: This is a retrospective, national database study with structured query of the Veterans Affairs (VA) database for patients who underwent BKA from 1999 to 2020, identified by Current Procedural Terminology codes. Above-knee amputation conversion was identified using Current Procedural Terminology codes in combination with natural language processing to match procedure laterality. After internally validating our patient identification method, risk factors were collected. Competing risk analysis estimated the cumulative incidence rate of AKA conversion and associated risk factors with death as a competing risk. RESULTS: Our query yielded 19,875 patients (19,640 men, 98.8%) who underwent BKA with a median age of 66 years (interquartile range, 60 to 73). The median follow-up was 951 days (interquartile range, 275 to 2,026). The crude cumulative probabilities of AKA conversion and death at 5 years were 15.4% (95% confidence interval [CI], 14.9% to 16.0%) and 47.7% (95% CI, 46.9% to 48.4%), respectively. In the Fine and Gray subdistribution hazard model, peripheral vascular disease had the highest AKA conversion risk (hazard ratio [HR] 2.66; 95% CI, 2.22 to 3.20; P < 0.001). Other factors independently associated with AKA conversion included urgent operation (HR 1.32; 95% CI, 1.23 to 1.42), cerebrovascular disease (HR 1.19; 95% CI, 1.11 to 1.28), chronic obstructive pulmonary disease (HR 1.15; 95% CI, 1.07 to 1.24), and previous myocardial infarction (HR 1.10; 95% CI, 1.02 to 1.19) (All P < 0.02). DISCUSSION: Within this predominantly male, VA population, BKA carries a high risk of conversion to AKA within 5 years, without reaching a steady risk of AKA conversion within 5 years. Peripheral vascular disease, chronic obstructive pulmonary disease, cerebrovascular disease, previous myocardial infarction, and urgent BKA increase the risk of AKA conversion. LEVEL OF EVIDENCE: Level III.

A Quality, Benefit, Cost, and Financial Framework for Health Information Technology, E-Prescribing: A Delphi Study.

BACKGROUND: Little research has been conducted about the quality, benefits, costs, and financial considerations associated with health information technology (HIT), particularly informatics technologies, such as e-prescribing, from the perspective of all its stakeholders. OBJECTIVES: This research effort sought to identify the stakeholders involved in e-prescribing and to identify and rank-order the positives and the negatives from the perspective of the stakeholders to create a framework to assist in the development of incentives and payment mechanisms which result in better managed care. METHODS: The Delphi method was employed by enlisting a panel of experts. They were presented with the results of initial research in an online survey of questions which sought to prioritize the quality, benefit, cost, and financial effects of e-prescribing from the perspective of each stakeholder. From the results of this study, a framework was presented to framework experts. RESULTS: The experts added stakeholders and positives and negatives to the initial lists and rank-ordered the positives and negatives of e-prescribing from the perspective of each stakeholder. The aggregate results were summarized by category of stakeholder. The framework experts evaluated the framework. CONCLUSIONS: Positives and negatives can be rank-ordered from the perspective of each stakeholder. A useful framework was created.

How Stakeholder Assessment of E-Prescribing Can Help Determine Incentives to Facilitate Management of Care: A Delphi Study.

BACKGROUND: Little research has been conducted on the quality, benefits, costs, and financial considerations associated with health information technology (HIT), particularly informatics technologies such as e-prescribing, from the perspective of all of its stakeholders. OBJECTIVES: To (a) identify the stakeholders involved in e-prescribing and (b) identify and rank order the positives and negatives of e-prescribing from the perspective of stakeholders in order to create a framework for payers, integrated delivery systems, policymakers and legislators, and those who influence public policy to assist them in the development of incentives and payment mechanisms that result in the better management of care. METHODS: The Delphi method was used to enlist a panel of experts in e-prescribing, informatics, and/or HIT who have published in the field. This panel was presented with the results of initial research and an online survey of questions that sought to prioritize the quality, benefit, cost, and financial effects of e-prescribing from the perspective of each stakeholder. Eleven experts completed the first survey, which contained a list of stakeholders and positives and negatives associated with e-prescribing. Nine of the 11 experts completed the second survey, and 7 experts completed the final survey. From the results of these 3 surveys, a framework was presented to 5 framework experts, who were representatives from payers, integrated delivery systems, policymakers and legislators, and those who influence public policy. These framework experts were interviewed regarding the usefulness of the framework from their perspectives. RESULTS: The experts added stakeholders and many positives and negatives to the initial list and rank ordered the positives and negatives of e-prescribing from the perspective of each stakeholder. The aggregate results were summarized by stakeholder category. The positives and negatives were categorized as health, finance, effort, time, management, or data concerns. The framework experts evaluated the framework and found it useful. CONCLUSIONS: Positives and negatives associated with e-prescribing in the areas of quality, benefits, costs, and financial considerations can be rank ordered from the perspective of each stakeholder. The experts agreed on some points but disagreed on others. For example, they agreed that the main negative of e-prescribing from the perspective of pharmacists and pharmacies was its implementation costs but differed on the importance of providing faster information transfer. A framework was created that could be successfully used by payers, integrated delivery systems, policymakers and legislators, and those who influence public policy for the development of incentives and payment mechanisms. DISCLOSURES: This research was supported by the National Library of Medicine of the National Institutes of Health under Award Number T15LM007088. The authors declare no conflicts of interest in the research. Study concept and design were contributed by DeMuro, Ash, Middleton, and Fletcher. DeMuro took the lead in data collection, along with Ash, and data interpretation was performed by DeMuro, Ash, Madison, Middleton, and Fletcher. The manuscript was written primarily by DeMuro, along with Ash and Middleton, and revised by DeMuro, Madison, and Ash, along with Middleton and Fletcher.