Differences in real-world outcomes by risk classification for localized prostate cancer patients after radiation therapy.

BACKGROUND: Limited real-world evidence exists on the long-term clinical outcomes of patients with localized prostate cancer (LPC) who received external beam radiation therapy (EBRT) as the initial treatment. This study evaluated clinical outcomes of US patients with high-risk LPC (HR-LPC) and low/intermediate-risk LPC (LIR-LPC) who received EBRT. METHODS: This retrospective study using Surveillance, Epidemiology, and End Results-Medicare linked data from 2012 to 2019 included patients ≥ 65 years old who received EBRT as initial therapy. Baseline patient characteristics were summarized, metastasis-free survival (MFS), overall survival, and time to initiation of advanced prostate cancer treatment were compared using Kaplan-Meier (KM) and adjusted Cox proportional hazard (PH) models. 5-year survival probabilities stratified by race/ethnicity (non-Hispanic [NH] White, NH Black, NH Asian, and Hispanic) were assessed. RESULTS: Of 11,313 eligible patients, 41% (n = 4600) had HR-LPC and 59% (n = 6713) had LIR-LPC. Patient characteristics for both groups were comparable, with mean age at EBRT initiation > 70 years, 86% white, and mean follow-up time >40 months. More patients in the HR-LPC than LIR-LPC groups (78% vs 34%) had concurrent androgen deprivation therapy use and for a longer duration (median 10.4 months vs. 7.4 months). A higher proportion of HR-LPC patients developed metastasis, died, or received advanced prostate cancer treatment. Adjusted Cox PH survival analyses showed significantly (p < 0.0001) higher risk of mortality (hazard ratios [HR], 1.57 [1.38, 2.34]), metastasis or death (HR, 1.97 [1.78, 2.17]), and advanced prostate cancer therapy use (HR, 2.57 [2.11, 3.14]) for HR-LPC than LIR-LPC patients. Within 5 years after the initial EBRT treatment, 18%-26% of patients with HR-LPC are expected to have died or developed metastasis. The 5-year MFS rate in the HR-LPC group was lower than the LIR-LPC group across all racial/ethnic subgroups. NH Black patients with HR-LPC had the highest all-cause mortality rate and lowest rate of receiving advanced prostate cancer treatment, compared to other racial/ethnic subgroups. CONCLUSIONS: This real-world study of clinical outcomes in patients with LPC treated with EBRT suggests substantial disease burden in patients with HR-LPC and highlights the need for additional treatment strategies to improve clinical outcomes in patients with HR-LPC.

Predicting Risk of 1-Year Hospitalization Among Patients with Pulmonary Arterial Hypertension.

INTRODUCTION: US claims-based analyses emphasize the substantial hospitalization burden of patients with pulmonary arterial hypertension (PAH) and the significant need for improved monitoring and more timely interventions. A claims-based predictive model may be useful to assist healthcare providers and payers in identifying patients with PAH at increased hospitalization risk. To address this aim, we constructed statistical models using baseline patient variables available in administrative healthcare claims to predict patients' risk for all-cause and PH-related hospitalization within 1 year of initiating ≥ 1 PAH indicated medication. METHODS: Adult patients with PAH who newly initiated ≥ 1 PAH indicated medication were selected from the MarketScan Commercial and Medicare Supplemental databases (January 1, 2009-January 31, 2019). Cox regression models were built with a randomly selected training set and evaluated using a validation set of remaining patients. Predictive variables for the models were selected in three steps: clinical knowledge, univariate analysis, and backward stepwise selection. RESULTS: Within 1 year of initiating ≥ 1 PAH indicated medication, 1502/3872 (38.8%) had an all-cause hospitalization and 950/3872 (24.5%) had a pulmonary hypertension (PH)-related hospitalization. Predictive risk factors for all-cause hospitalization were Quan-Charlson Comorbidity Index (CCI) score 2-3 [hazard ratio (HR) 1.229; P = 0.038] and ≥ 4 (HR 1.531; P < 0.001), claims-based frailty index (CFI) score > 1 (highest frailty level; HR 1.301; P = 0.018), hemoptysis (HR 1.254; P = 0.016), malaise/fatigue (HR 1.150; P = 0.037), history of PH-related hospitalization (HR 1.171; P = 0.011), non-PH-related ER visit (HR 1.713; P = 0.014), and higher non-PH-related outpatient visit cost (HR 1.069; P < 0.001). Predictive risk factors for PH-related hospitalization were female sex (HR 1.264; P = 0.004), Quan-CCI score ≥ 4 (HR 1.408; P = 0.008), portal hypertension (HR 1.565; P = 0.019), CFI score > 1 (HR 1.522; P = 0.002), dyspnea (HR 1.259; P = 0.023), and history of PH-related hospitalization (HR 1.273; P = 0.002). CONCLUSIONS: The US claims-based predictive models showed acceptable performance to predict 1-year hospitalization among patients with PAH.

Efficacy of Transabdominal Ultrasound-guided Percutaneous Microwave Ablation in the Treatment of Symptomatic Adenomyosis: A Retrospective Cohort Study.

STUDY OBJECTIVE: To evaluate and compare the clinical efficacy of transabdominal ultrasound-guided percutaneous microwave ablation (PMWA) in the treatment of symptomatic focal and nonfocal adenomyosis. DESIGN: Retrospective cohort study. SETTING: Longyan First Affiliated Hospital of Fujian Medical University. PATIENTS: From May 2019 to October 2021, 107 patients with symptomatic adenomyosis who refused hysterectomy received PMWA. INTERVENTIONS: Patients were divided into a focal group (n = 47, including 40 focal adenomyosis and 7 adenomyoma cases) and a nonfocal group (n = 60, including 36 diffuse and 24 mixed adenomyosis cases) according to the extent of lesion involvement. MEASUREMENTS AND MAIN RESULTS: We collected and analyzed preoperative baseline data on patient characteristics; postoperative efficacy measures at 3, 6, and 12 months; and intraoperative and postoperative complications. There was a significant post-treatment reduction in the uterine corpus volume and cancer antigen 125 levels, an increase in hemoglobin levels, and an improvement in the Uterine Fibroid Symptom and Health-related Quality of Life scores (consisting of the Symptom Severity Scale and the Health-related Quality of Life scale), dysmenorrhea visual analog scale, and menstrual volume score (MVS) (all p <.05). One patient had recurrence. Most adverse events (72.0%) were mild. Although the nonfocal group had significantly greater anemia severity, higher Symptom Severity Scale and MVS, lower Health-related Quality of Life scale, greater extent and severity of myometrial involvement, and larger uterine corpus volume, after treatment, the uterine corpus volume, uterine corpus reduction rate, cancer antigen 125 levels, hemoglobin levels, Uterine Fibroid Symptom and Health-related Quality of Life score, dysmenorrhea visual analog scale, MVS score, and clinical response rate were similar between the groups (p >.05). CONCLUSION: PMWA had good, similar, short-term efficacy for symptomatic focal and nonfocal adenomyosis.

Combined transabdominal and transvaginal ultrasound-guided percutaneous microwave ablation of uterine myomas: an effective monitoring technique.

OBJECTIVE: This study compared the feasibility and efficacy of transabdominal ultrasound (TAU) and combined transabdominal and transvaginal ultrasound (TA/TV US)-guided percutaneous microwave ablation (PMWA) for uterine myoma (UM). METHOD: This study enrolled 73 patients with UM who underwent PMWA via the transabdominal ultrasound-guided (TA group) or the combined transabdominal and transvaginal ultrasound-guided (TA/TV group) approaches. The intraoperative supplementary ablation rates, postoperative immediate ablation rates, lesion reduction rates and other indicators three months postoperatively were compared between the groups. The display of the needle tip, endometrium, uterine serosa, rectum and myoma feeding vessels under the guidance of TAU, transvaginal ultrasound (TVU) and TA/TV US were evaluated in the TA/TV group. RESULTS: In the TA/TV group, the real-time position of the needle tip and the endometrium complete display rate of the same lesions with TVU guidance were significantly higher than those using TAU. TA/TV US guidance significantly improved the complete display rate of each indicator. The intraoperative supplementary ablation rate in the TA/TV group was lower than that in the TA group. Similarly, the postoperative immediate ablation and volume reduction rates of the lesions three months postoperatively were higher than those in the TA group, especially for lesions with a maximum diameter ≥6 cm. CONCLUSION: TA/TV US is an effective monitoring method that can be used to improve imaging display. Its use is recommended in patients with obesity, poor transabdominal ultrasound image quality and large myoma volumes.

Three-dimensional ultrasound VOCAL combined with contrast-enhanced ultrasound: an alternative to contrast-enhanced magnetic resonance imaging for evaluating ablation of benign uterine lesions.

OBJECTIVE: This study explores the feasibility and value of three-dimensional ultrasound virtual organ computer-aided analysis (3D-VOCAL) combined with contrast-enhanced ultrasound (CEUS) for measuring the non-perfused volume (NPV) after microwave ablation (MWA) of benign uterine lesions. METHODS: Fifty-six patients with uterine myoma (UM) and adenomyosis (AM) treated with MWA were enrolled. NPV measurements were obtained postoperatively using two-dimensional CEUS (2D-CEUS), 3D-VOCAL combined with CEUS and three-dimensional contrast-enhanced magnetic resonance imaging (3D-CEMRI). Bland-Altman analysis and intraclass correlation coefficient (ICC) values were used to analyze the agreement of NPV measurements obtained via 2D-CEUS and the combined method with 3D-CEMRI. The inter- and intra-observer agreements of the NPV values obtained with all three methods were also analyzed. RESULTS: Considering 3D-CEMRI as the standard, 3D-VOCAL showed greater agreement than 2D-CEUS and higher ICCs (ICC, 0.999 vs. 0.891) than 2D-CEUS for different lesion types and sizes of non-perfusion areas (p < 0.001 for all comparisons). NPV measurements obtained via 2 D-CEUS and 3 D-CEMRI differed significantly for AM and non-perfusion areas with maximum diameter ≥5 cm (p < 0.05) and showed no significant differences (p > 0.05) for UM and non-perfusion areas with maximum diameter <5 cm. The NPV measurements obtained via 3D-VOCAL and 3D-CEMRI did not differ significantly (p > 0.05). The intra- and inter-observer agreements of 3D-VOCAL measurements were better than those of 2D-CEUS and slightly lower than those of 3D-CEMRI. CONCLUSIONS: 3D-VOCAL combined with CEUS provides accurate estimates of NPV after MWA of benign uterine lesions, and offers a reliable, simple and efficient alternative to CEMRI.

Real-World Patient Characteristics, Treatment Patterns, and Mutation Testing Patterns Among US Patients with Advanced Non-Small Cell Lung Cancer Harboring EGFR Mutations.

INTRODUCTION: Approximately 15% of patients with non-small cell lung cancer (NSCLC) harbor an epidermal growth factor receptor mutation (EGFRm). Mutation testing (including EGFRm) is recommended for patients with advanced NSCLC (aNSCLC) prior to initiating first-line therapy (L1) or after progression on targeted therapy. To elucidate current and future unmet needs, the present study characterized real-world EGFR testing patterns and treatment patterns in patients with aNSCLC. METHODS: This retrospective observational cohort study evaluated newly diagnosed adult patients with aNSCLC (stage IIIB or higher) from the Flatiron Health database. Eligible patients received at least L1 during 2015-2020 (testing cohorts) or 2011-2020 (treatment cohorts). Eligible patients for the treatment cohorts had an EGFR mutation. RESULTS: The testing cohort included 22,726 patients, 75.5% had at least one EGFR test and 15.2% of those tested were positive for EGFR mutation. From 2015 to 2020, the median time from sample collection to test results decreased substantially while the proportion of NGS EGFR tests and use of plasma samples increased. The treatment cohort included 3701 patients (95% common mutations [cEGFR], 5.0% exon 20 insertions [ex20ins]). Three or more lines of therapy (LOTs) were observed in approximately 30% of patients. For L1, most cEGFR patients received EGFR tyrosine kinase inhibitors (EGFR-TKI, 68.1%) or platinum-based chemotherapy (PBC, 24.8%); most ex20ins patients received PBC (66.1%) or EGFR-TKI (17.5%). The most common L2 was EGFR-TKI (54.1%) or PBC (22.8%) for cEGFR and immunotherapy (25.9%) or PBC (25.9%) for ex20ins. No predominant L3 was evident in either group. CONCLUSION: This real-world study, among the largest analyses of testing patterns for patients with aNSCLC, demonstrates a comprehensive view of treatment patterns for patients with EGFR mutations, including ex20ins. Despite recent improvement, increased use of EGFR testing, including advanced methods, is needed to optimize treatment pathways and outcomes. Additionally, the lack of a predominant therapy in later lines indicates a need for new therapies.

The Brassicaceae genome resource (TBGR): A comprehensive genome platform for Brassicaceae plants.

The Brassicaceae is an important plant family. We built a user-friendly, web-based, comparative, and functional genomic database, The Brassicaceae Genome Resource (TBGR, http://www.tbgr.org.cn), based on 82 released genomes from 27 Brassicaceae species. The TBGR database contains a large number of important functional genes, including 4,096 glucosinolate genes, 6,625 auxin genes, 13,805 flowering genes, 36,632 resistance genes, 1,939 anthocyanin genes, and 1,231 m6A genes. A total of 1,174,049 specific guide sequences for clustered regularly interspaced short palindromic repeats and 5,856,479 transposable elements were detected in Brassicaceae. TBGR also provides information on synteny, duplication, and orthologs for 27 Brassicaceae species. The TBGR database contains 1,183,851 gene annotations obtained using the TrEMBL, Swiss-Prot, Nr, GO, and Pfam databases. The BLAST, Synteny, Primer Design, Seq_fetch, and JBrowse tools are provided to help users perform comparative genomic analyses. All the genome assemblies, gene models, annotations, and bioinformatics results can be easily downloaded from the TBGR database. We plan to improve and continuously update the database with newly assembled genomes and comparative genomic studies. We expect the TBGR database to become a key resource for the study of the Brassicaceae.

Healthcare Costs of Multiple Myeloma Patients with Four or More Prior Lines of Therapy, Including Triple-Class Exposure in the United States.

INTRODUCTION: The treatment of multiple myeloma (MM) remains a challenge as patients eventually progress through several lines of therapy (LOTs), requiring use of multiple MM drug classes. In this retrospective US claims-database study, we examined the healthcare costs of patients with MM who received ≥ 4 prior LOTs, including triple-class exposure (TCE). METHODS: Adult patients with MM were selected from the IBM MarketScan Commercial and Medicare claims databases (1 January 2012-30 June 2021). Eligible patients were required to have received at least four prior LOTs, and TCE (i.e., received a proteasome inhibitor, immunomodulatory drug, and anti-CD38-targeted monoclonal antibody) after the first-observed diagnosis of MM. The index date was defined as the initiation date of the first subsequent LOT after meeting the eligibility criteria for the study, and this date had to be after 1 January 2017 to capture contemporary cost estimates. The primary outcome measurements were all-cause and MM-related healthcare costs after the index date. RESULTS: The study population included 68 patients with MM (63% men), with a mean age of 59.8 years. Mean duration from first-observed MM diagnosis until index date averaged 46.7 months. During a mean follow-up of 21.9 months, total all-cause healthcare costs averaged US$757,386 per patient (equivalent to US$34,610 per patient per month). MM-related healthcare costs (US$670,561 per patient) contributed on average 88.5% to the total all-cause healthcare costs; the majority (67.2%) of MM-related healthcare costs were attributed to drug and infusion costs (US$450,952 per patient). CONCLUSIONS: In this retrospective US claims-database study, patients with MM with ≥ 4 prior LOTs, including TCE, continued to experience high healthcare costs that were mostly attributable to anti-myeloma drugs and their administration.

Interleukin-17 and vascular endothelial growth factor: new biomarkers for the diagnosis of papillary thyroid carcinoma in patients with Hashimoto's thyroiditis.

OBJECTIVE: The incidences of papillary thyroid carcinoma (PTC) and Hashimoto's thyroiditis (HT) have shown increasing trends. Numerous studies have shown a close relationship between the two diseases, but the exact mechanism linking PTC with HT is still unclear. Interleukin-17 (IL-17) plays an important role in the development of malignant tumors. However, information on the association between IL-17 and thyroid disease is lacking. METHODS: Tissue samples were collected from patients with thyroid diseases admitted to the thyroid surgery department of our hospital between May 2015 and December 2017. The characteristics of the thyroid were observed by ultrasonography, hematoxylin-eosin staining, enzyme-linked immunosorbent assays, and immunohistochemistry. RESULTS: We found that HT with carcinoma (HTC) showed unique characteristics in two-dimensional ultrasound images. Moreover, IL-17 and vascular endothelial growth factor (VEGF) levels showed gradually increasing trends during the process of HT malignant transformation, with a significant positive correlation between the two cytokines. Serum IL-17 and VEGF levels could distinguish between HTC and HT with benign adenoma. CONCLUSION: Our data suggest that serum IL-17 and VEGF levels may represent novel biomarkers for the diagnosis of HT malignant nodules.

Effectiveness and Safety of Rivaroxaban versus Warfarin Among Nonvalvular Atrial Fibrillation Patients with Obesity and Polypharmacy.

BACKGROUND: Current evidence suggests that rivaroxaban may be well tolerated and effective in patients with nonvalvular atrial fibrillation (NVAF) and obesity; however, there is limited evidence on the impact of polypharmacy in this population. This study evaluated real-world clinical outcomes with rivaroxaban versus warfarin in patients with NVAF and obesity according to the number of concurrent medications. METHODS: This retrospective cohort study identified patients with one or more pharmacy claim for rivaroxaban or warfarin from two large claims databases. Patients were required to have an atrial fibrillation diagnosis, body mass index ≥ 30 kg/m2 and the presence of polypharmacy (1-4, 5-9, or ≥ 10 concurrent medications). Outcomes of stroke, systemic embolism, and major bleeding were compared between the rivaroxaban and warfarin cohorts after propensity score matching (PSM). RESULTS: A total of 95,875 patients were identified with one or more claim for either rivaroxaban or warfarin. After PSM, patient characteristics were balanced between cohorts (n = 21,547 in each cohort). The overall composite risk of stroke and systemic embolism was significantly lower in the rivaroxaban cohort compared with the warfarin cohort (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.70-0.84; p < 0.001). The risks of ischemic stroke, hemorrhagic stroke, and systemic embolism separately were also significantly reduced with rivaroxaban. Major bleeding risk was similar between cohorts (HR 0.93, 95% CI 0.81-1.06; p = 0.2842), and results were consistent across the three polypharmacy groups. CONCLUSIONS: In this real-world study of NVAF patients with obesity, rivaroxaban was associated with lower risks of stroke and systemic embolism and similar risk of major bleeding versus warfarin across polypharmacy categories.

Healthcare Costs Incurred by Patients with Multiple Myeloma Following Triple Class Exposure (TCE) in the US.

INTRODUCTION: Multiple myeloma (MM) is a malignancy of plasma cells; most MM patients will eventually relapse or become refractory to treatment. Treating MM patients remains a challenge since patients eventually progress through several lines of therapy (LOTs), requiring the use of multiple MM drug classes. We examined healthcare resource utilization (HCRU) and the costs incurred by MM patients following triple class exposure (TCE; defined as exposure to a proteosome inhibitor, an immunomodulatory agent, and an anti-CD-38 antibody). METHODS: Adult MM patients were selected from the MarketScan® commercial and Medicare supplemental databases (January 2009-February 2021). From this cohort, patients who had TCE and ≥ 1 subsequent LOT that occurred after January 1, 2017 were included in the study population. The initiation date for the first post-TCE LOT was defined as the index date. All-cause and MM-related HCRU and the associated costs were examined post-index date. RESULTS: A total of 85 MM patients with TCE who initiated ≥ 1 subsequent LOT post-TCE and had ≥ 1 year of follow-up post-index date were included in the study population; mean age on index date was 58.8 years, and 60.0% were male. The time from first-observed MM diagnosis until index date averaged 47.5 months. During an average follow-up of 20.9 months post-index date, 64.7% of patients (N = 55) initiated a second LOT and 35.2% (N = 30) received at least 3 LOTs. During follow-up, mean total all-cause healthcare cost per patient was $722,992 (equivalent to $34,578 per patient per month [PPPM]). Approximately 90.7% ($655,524 per patient) of the total all-cause healthcare costs were MM related, 66.0% of which were MM drug/infusion costs. CONCLUSION: In this real-world US study, MM patients with TCE incurred high healthcare costs, with the majority being MM related and primarily attributed to MM drug and infusion costs.

Healthcare Resource Utilization and Costs of Rivaroxaban Versus Warfarin Among Nonvalvular Atrial Fibrillation Patients with Obesity and Diabetes.

INTRODUCTION: Nonvalvular atrial fibrillation (NVAF) is associated with a substantial economic burden, particularly in patients with comorbid conditions. This study compared healthcare resource utilization (HRU) and costs of rivaroxaban and warfarin in patients with NVAF, obesity, and diabetes. METHODS: A de-identified healthcare claims database was used to identify adult patients newly initiating rivaroxaban or warfarin and having at least one medical claim with a diagnosis of AF, obesity determined by validated algorithm, and at least one claim with a diagnosis of diabetes or for antidiabetic medication from December 2011 to March 2020. Propensity score matching was used to balance the treatment cohorts on the basis of demographics and baseline characteristics. All-cause and NVAF-related HRU rates and costs were compared between treatments using rate ratios, and mean cost differences were calculated on a per patient per year (PPPY) basis. RESULTS: A total of 9999 matched pairs of patients with NVAF, obesity, and diabetes were identified in the rivaroxaban and warfarin cohorts. Rate ratios of all-cause HRU were significantly reduced with rivaroxaban versus warfarin in all healthcare settings evaluated, except emergency room visits. The greatest impact was on physician office visits followed by hospital outpatient and inpatient visits. NVAF-related HRU was significantly lower for rivaroxaban versus warfarin in all care settings. Consistent with these findings, the length of hospital stay was significantly reduced by approximately 4 days among all patients for both all-cause and NVAF-related hospitalizations in the rivaroxaban cohort compared with the warfarin cohort. Rivaroxaban was associated with reductions in all-cause total healthcare costs by more than $5000 PPPY and NVAF-related medical costs by approximately $1100 PPPY. CONCLUSION: In comparison with warfarin, rivaroxaban reduced HRU and costs, particularly hospital inpatient and outpatient visits and physician office visits, in patients with NVAF and comorbidities of obesity and diabetes.

People who are overweight or obese are at risk of developing atrial fibrillation (AF) along with other medical conditions, such as diabetes. Standard therapy with oral anticoagulants or blood thinners is recommended to reduce the risk of stroke and systemic embolism in patients with nonvalvular AF (NVAF). In this study, we evaluated healthcare insurance claims for people with NVAF, obesity, and diabetes who started therapy with warfarin or rivaroxaban from 2011 to 2020 to compare the use and cost of healthcare services, such as hospitalizations and doctor visits, using diagnosis and procedure codes. The study included nearly 20,000 patients with similar characteristics. Patients who started treatment with rivaroxaban used fewer healthcare services for any cause and for those related to NVAF than those who started treatment with warfarin. The difference in use of services was largest for hospital outpatient and inpatient visits and doctor office visits; emergency room visits were only different for those related to NVAF. Length of hospital stay was also shorter for patients receiving rivaroxaban versus those receiving warfarin. These differences in healthcare service use translated into lower costs associated with rivaroxaban versus warfarin. The findings of this study suggest that treatment with rivaroxaban reduces the use of healthcare services compared with warfarin. This difference may be related, in part, to the reduced risks of stroke and systemic embolism observed in other real-world studies with rivaroxaban compared to warfarin. In addition, rivaroxaban does not require routine blood testing, which is required with warfarin treatment.

Effectiveness and safety of rivaroxaban versus warfarin among nonvalvular atrial fibrillation patients with obesity and diabetes.

AIMS: To compare clinical outcomes of rivaroxaban and warfarin in patients with nonvalvular atrial fibrillation (NVAF) and concurrent obesity and diabetes. METHODS: Patients aged ≥18 years were identified from a healthcare claims database with the following criteria: newly initiating rivaroxaban or warfarin, ≥1 medical claim with a diagnosis of AF, obesity determined by validated machine learning algorithm, and ≥1 claim with a diagnosis of diabetes or for antidiabetic medication. Treatment cohorts were matched using propensity scores and were compared for stroke/systemic embolism (SE) and major bleeding using Cox proportional hazards models. RESULTS: A total of 9999 matched pairs of NVAF patients with obesity and diabetes who initiated treatment with rivaroxaban or warfarin were included. The composite risk of stroke/SE was significantly lower in the rivaroxaban cohort compared with the warfarin cohort (HR 0.82; 95% CI 0.74-0.90). Risks of ischemic and hemorrhagic strokes were also significantly reduced with rivaroxaban versus warfarin, but not SE. Major bleeding risk was similar between treatment cohorts (HR 0.92; 95% CI 0.78-1.09). CONCLUSIONS: In NVAF patients with comorbidities of obesity and diabetes, rivaroxaban was associated with lower risks of stroke/SE and similar risk of major bleeding versus warfarin.

Association of depression symptom severity with short-term risk of an initial hospital encounter in adults with major depressive disorder.

BACKGROUND: Despite the availability of pharmacologic and nonpharmacologic treatment options, depression continues to be one of the leading causes of disability worldwide. This study evaluated whether depression symptom severity, as measured by PHQ-9 score, of patients diagnosed with MDD is associated with short-term risk of a hospital encounter (ER visit or inpatient stay). METHODS: Adults with ≥1 PHQ-9 assessment in an outpatient setting (index date) and ≥ 1 MDD diagnosis within 6 months prior were included from the de-identified Optum Electronic Health Record database (April 2016-June 2019). Patients were categorized by depression symptom severity based on PHQ-9 scores obtained by natural language processing. Crude rates, adjusted absolute risks, and adjusted relative risks of all-cause and MDD-related hospital encounters within 30 days following assessment of depression severity were determined. RESULTS: The study population consisted of 280,145 patients with MDD and ≥ 1 PHQ-9 assessment in an outpatient setting. Based on PHQ-9 scores, 26.9% of patients were categorized as having none/minimal depression symptom severity, 16.4% as mild, 24.7% as moderate, 19.6% as moderately severe, and 12.5% as severe. Among patients with none/minimal, mild, moderate, moderately severe, and severe depression, the adjusted absolute short-term risks of an initial all-cause hospital encounter were 4.1, 4.4, 4.8, 5.6, and 6.5%, respectively; MDD-related hospital encounter adjusted absolute risks were 0.8, 1.0, 1.3, 1.6, and 2.1%, respectively. Compared to patients with none/minimal depression symptom severity, the adjusted relative risks of an all-cause hospital encounter were 1.60 (95% CI 1.50-1.70) for those with severe, 1.36 (1.29-1.44) for those with moderately severe, 1.18 (1.12-1.25) for those with moderate, and 1.07 (1.00-1.13) for those with mild depression symptom severity. CONCLUSIONS: These study findings indicate that depression symptom severity is a key driver of short-term risk of hospital encounters, emphasizing the need for timely interventions that can ameliorate depression symptom severity.

Evaluation of Different Anthropometric Indicators for Screening for Nonalcoholic Fatty Liver Disease in Elderly Individuals.

OBJECTIVE: To explore the anthropometric indicators suitable for screening for nonalcoholic fatty liver disease (NAFLD) in the elderly population. METHODS: This cross-sectional study screened subjects over 65 years, who had undergone a physical examination in 2019. Their height, weight, waist circumference, and fasting blood glucose and triglyceride levels were measured. Body mass index (BMI), waist circumstance (WC), waist-to-height ratio (WHtR), relative fat mass (RFM), ponderal index (PI), conicity index (CI), lipid accumulation product (LAP), and body shape index (ABSI) were calculated. Statistical analyses were performed using the Chi-square test, logistic regression, and receiver operating characteristic (ROC) curve. SUBJECTS: Of a total of 4985 subjects, 1173 diagnosed with NAFLD and 3812 without NAFLD were included. RESULTS: The NAFLD group had increased BMI, WC, WHtR, RFM, PI, CI, and LAP. ABSI was only significantly different in males between the groups. Logistic regression analysis showed that RFM was an effective prognostic factor for males with NAFLD, and LAP, BMI, and WC were effective prognostic factors for females. ROC curve analysis showed that LAP played a significant role in the prediction of NAFLD. CONCLUSION: LAP is closely related to the occurrence of NAFLD and could be an efficient screening and treatment tool for NAFLD in the elderly people. Lay Summary. We conducted a screening and study of nonalcoholic fatty liver disease in the elderly population by determining the association between obesity indexes and nonalcoholic fatty liver disease. We found that LAP is practical, easy-to-measure tool for screening and studying NAFLD in the high-risk community elderly population, making it a valuable indicator in research.

Association of clinico-genomic characteristics with tumor mutational burden in small cell lung cancer patients.

Aim: We evaluated the relationship between clinical and genomic characteristics and tumor mutational burden (TMB) in small cell lung cancer. Materials & methods: In a retrospective analysis of small cell lung cancer patients aged ≥18, we assessed treatment patterns and survival in relation to TMB; the association of clinical and genomic characteristics with TMB was determined by multivariate regression. High TMB (TMB-H) was defined as ≥10 mutations/megabase. Results: Among 186 patients, treatment patterns and overall survival were similar for TMB-H and non-TMB-H patients. TMB was determined for 179 patients, 41.9% of whom were TMB-H. Short variants of LRP1B, FAT3, MLL3, MED12 and NOTCH3 were significantly associated with TMB-H (p ≤ 0.01). Conclusion: Neither treatment patterns nor survival differed by TMB status.

Reducing Uninformative IND Safety Reports: A List of Serious Adverse Events anticipated to Occur in Patients with Lung Cancer.

Expedited reporting of unexpected serious adverse reactions that occur during clinical trials conducted under an IND is a critical component of the clinical trial process designed to protect patients by identifying potential safety issues with new agents. However, in recent years, the US FDA has presented extensive data about the problem of uninformative IND safety reporting. Despite published guidance documents aimed at clarifying requirements for submission of IND safety reports for individual events, there continues to be significant over-reporting of these events by many sponsors. This leads to excessive burden for the sponsors, the investigators who conduct clinical trials, and the FDA reviewers, who must evaluate each individual report submitted by the sponsor. This trend has the potential to endanger patients by obscuring true safety signals. To address this problem, LUNGevity Foundation empaneled a multi-sector working group of its Scientific and Clinical Research Roundtable (SCRT) charged with identifying ways to reduce unnecessary distribution of serious adverse events (SAEs) reports. This paper outlines the working group's activities, including a brief list of serious adverse events "anticipated" to occur within the lung cancer population that are either related to the underlying disease or condition being studied, concomitant or background therapy, or events associated with a demographic parameter such as age. These "anticipated" events, while required to be reported by investigators to sponsors, in general, should not then be individually reported by sponsors to FDA and to individual investigators in an IND safety report because these events require aggregate analysis across the development program to determine if they occur more frequently in treated versus untreated patients. This paper also includes discussion of how the use of background threshold values, generated from real-world data, could serve as one potential tool to guide sponsors in making causality assessments. If sponsors and other key stakeholders within the clinical research ecosystem embrace this type of approach and refrain from reporting "anticipated" events as single IND safety reports to the FDA staff and to each participating investigator, it could significantly reduce the amount of unnecessary reporting and serve as a model for other disease areas.

Chemotherapy treatments, costs of care, and survival for elderly patients diagnosed with cervical cancer: an observational study.

Objective: To describe chemotherapy treatments, associated health care use and costs, and survival for women diagnosed with cervical cancer in the United States.Methods: This was a retrospective cohort study of patients aged ≥65 years, identified in linked Surveillance, Epidemiology, and End Results (SEER) and Medicare databases. Women with a new primary diagnosis of cervical cancer between January 2007 and December 2013 were followed until December 2014. Systemic chemotherapy treatments, health care visits and costs (2016 USD rates), and survival were determined by the line of therapy.Results: Of 1651 women in the analysis, 810 (49.1%) were diagnosed at stages I or II, 411 (24.9%) at stage III, and 430 (26.0%) at stage IV. A total of 225 (13.6%) women received first-line (1L) systemic chemotherapy. Of those who received 1L chemotherapy, 73 (32.4%) received second-line (2L) chemotherapy, and 29 (12.9%) received third-line (3L) chemotherapy. During 1L and 2L chemotherapies, patients averaged 5.9 and 6.5 health care visits per month, respectively, and incurred total mean health care costs per patient per month of $7098 and $8770, respectively. Median survival from the start of 1L and 2L chemotherapy was 14.0 and 10.4 months, respectively.Conclusion: Elderly patients with advanced cervical cancer had a poor prognosis, with a median survival of 14 months or less, and had no standard of care for 2L therapy. Systemic chemotherapies pose a substantial economic burden in the range of $7000 to $9000 per patient per month. These results highlight the high unmet medical need among elderly patients with cervical cancer.

Survival, Chemotherapy Treatments, and Health Care Utilization Among Patients with Advanced Small Cell Lung Cancer: An Observational Study.

INTRODUCTION: Most cases of small cell lung cancer (SCLC) are diagnosed at an advanced stage. The objective of this study was to investigate patient characteristics, survival, chemotherapy treatments, and health care use after a diagnosis of advanced SCLC in subjects enrolled in a health system network. METHODS: This was a retrospective cohort study of patients aged ≥ 18 years who either were diagnosed with stage III/IV SCLC or who progressed to advanced SCLC during the study period (2005-2015). Patients identified from the Indiana State Cancer Registry and the Indiana Network for Patient Care were followed from their advanced diagnosis index date until the earliest date of the last visit, death, or the end of the study period. Patient characteristics, survival, chemotherapy regimens, associated health care visits, and durations of treatment were reported. Time-to-event analyses were performed using the Kaplan-Meier method. RESULTS: A total of 498 patients with advanced SCLC were identified, of whom 429 were newly diagnosed with advanced disease and 69 progressed to advanced disease during the study period. Median survival from the index diagnosis date was 13.2 months. First-line (1L) chemotherapy was received by 464 (93.2%) patients, most commonly carboplatin/etoposide, received by 213 (45.9%) patients, followed by cisplatin/etoposide (20.7%). Ninety-five (20.5%) patients progressed to second-line (2L) chemotherapy, where topotecan monotherapy (20.0%) was the most common regimen, followed by carboplatin/etoposide (14.7%). Median survival was 10.1 months from 1L initiation and 7.7 months from 2L initiation. CONCLUSION: Patients in a regional health system network diagnosed with advanced SCLC were treated with chemotherapy regimens similar to those in earlier reports based on SEER-Medicare data. Survival of patients with advanced SCLC was poor, illustrating the lack of progress over several decades in the treatment of this lethal disease and highlighting the need for improved treatments.

Chemotherapy treatments, costs of care, and survival for patients diagnosed with small cell lung cancer: A SEER-Medicare study.

OBJECTIVES: The effectiveness and costs of new treatments should be assessed in relation to existing practice. We describe treatments, survival and costs for advanced or metastatic small cell lung cancer (SCLC) patients receiving systemic therapy in the period preceding the introduction of immunotherapies. MATERIALS AND METHODS: This was a retrospective cohort study of patients aged ≥65 years, identified using linked Surveillance, Epidemiology, and End Results and Medicare databases. Individuals with a new primary diagnosis of SCLC between January 2007 and December 2013 were followed until December 2014. Chemotherapy treatments, health care visits and costs (in 2016 USD), and survival were determined by line of therapy. RESULTS: A total of 11 812 patients were identified with SCLC. First-line (1L) chemotherapy was received by 6509 (55.1%) patients, most (93.2%) with carboplatin- (71.0%) or cisplatin- (22.2%) based therapies, typically combined with etoposide (79.2%). Second- (2L) and third- (3L) line chemotherapies were received by 2238 (18.9%) and 679 (5.7%) patients, of which 48.4% and 30.9%, respectively, were platinum-based. The median durations of 1L, 2L, and 3L carboplatin-based therapies were 5.9, 4.8, and 5.4 months, respectively, and the corresponding durations of cisplatin-based therapies were 5.3, 4.2, and 5.3 months. During 1L, 2L, and 3L chemotherapies, patients averaged 8.2, 7.4, and 7.3 health care visits per month, respectively, and incurred total mean health care costs of $60 223, $42 636, and $35 903 per patient, respectively. Median survival from the start of 1L, 2L, and 3L chemotherapy was 9.2, 6.0, and 5.7 months, respectively. CONCLUSION: First-line chemotherapy was primarily platinum-based, and a plethora of different regimens was used for 2L and 3L chemotherapies. Median survival from the start of 1L chemotherapy was 9 months, with an associated health care cost of $60 000. These data highlight an unmet medical need among SCLC patients receiving systemic therapy.