Comparison of Comorbidity Models Within a Population-Based Cohort of Older Adults With Non-Hodgkin Lymphoma.

PURPOSE: Compare the association of individual comorbidities, comorbidity indices, and survival in older adults with non-Hodgkin lymphoma (NHL), including in specific NHL subtypes. METHODS: Data source was SEER-Medicare, a population-based registry of adults age 65 years and older with cancer. We included all incident cases of NHL diagnosed during 2008-2017 who met study inclusion criteria. Comorbidities were classified using the three-factor risk estimate scale (TRES), Charlson comorbidity index (CCI), and National Cancer Institute (NCI) comorbidity index categories and weights. Overall survival (OS) and lymphoma-specific survival, with death from other causes treated as a competing risk, were estimated using the Kaplan-Meier method from time of diagnosis. Multivariable Cox models were constructed, and Harrel C-statistics were used to compare comorbidity models. A two-sided P value of <.05 was considered significant. RESULTS: A total of 40,486 patients with newly diagnosed NHL were included. Patients with aggressive NHL had higher rates of baseline comorbidity. Despite differences in baseline comorbidity between NHL subtypes, cardiovascular, pulmonary, diabetes, and renal comorbidities were frequent and consistently associated with OS in most NHL subtypes. These categories were used to construct a candidate comorbidity score, the non-Hodgkin lymphoma 5 (NHL-5). Comparing three validated comorbidity scores, TRES, CCI, NCI, and the novel NHL-5 score, we found similar associations with OS and lymphoma-specific survival, which was confirmed in sensitivity analyses by NHL subtypes. CONCLUSION: The optimal measure of comorbidity in NHL is unknown. Here, we demonstrate that the three-category TRES and five-category NHL-5 scores perform as well as the 14-16 category CCI and NCI scores in terms of association with OS and lymphoma-specific survival. These simple scores could be more easily used in clinical practice without prognostic loss.

Association of Age with Non-muscle-invasive Bladder Cancer: Unearthing a Biological Basis for Epidemiological Disparities?

BACKGROUND: Age disparity in patients with non-muscle-invasive bladder cancer (NMIBC) exists. Whether this is due to differences in adequate cancer care or tumour biology is unclear. OBJECTIVE: To investigate age disparities in NMIBC using the Surveillance, Epidemiology, and End Results (SEER)-Medicare and UROMOL datasets. DESIGN, SETTING, AND PARTICIPANTS: The SEER-Medicare data were used to identify patients with clinical stage Ta, Tis, and T1 NMIBC between 2005 and 2017 (n = 32 225). Using the UROMOL cohort (n = 834), age disparities across transcriptomic, genomic, and spatial proteomic domains were assessed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: For the SEER-Medicare data, multivariable competing-risk regression was used to examine the association between age and recurrence, progression, and bladder cancer-specific mortality (BCSM). For the UROMOL cohort, multivariable general linear model and multinomial logistic regression were performed to evaluate the association between age and tumour biology. RESULTS AND LIMITATIONS: An analysis of the SEER-Medicare cohort revealed 5-yr recurrence rates of 55.2%, 57.4%, and 58.9%; 5-yr progression rates of 25.6%, 29.2%, and 36.9%; and 5-yr BCSM rates of 3.9%, 5.8%, and 11.8% in patients aged 66-70, 71-80, and ≥81 yr, respectively. After multivariable adjustment, age ≥81 yr was associated with a higher risk of recurrence (hazard ratio [HR] 1.07, 95% confidence interval [CI] 1.03-1.12; p = 0.001), progression (HR 1.32, p < 0.001), and BCSM (HR 2.58, p < 0.001). UROMOL2021 transcriptomic class 2a was most frequently observed in patients with advanced age (34.0% in ≥76 yr vs 21.6% in ≤65 yr; p = 0.004), a finding confirmed on multivariable analysis (risk ratio [RR] 3.86, p = 0.002). UROMOL2021 genomic class 3 was observed more frequently in patients aged ≥76 yr (4.9% vs 24.2%; p = 0.001). Limitations include the definitions used for recurrence and progression, which may lead to under- or overestimation of true rates. CONCLUSIONS: Among SEER-Medicare patients with NMIBC, advanced age is associated with inferior oncological outcomes. These results reflect age-related molecular biological differences observed across transcriptomic and genomic domains, providing further evidence that innate tumour biology contributes to observed disparities in NMIBC outcomes. PATIENT SUMMARY: Older patients with non-muscle-invasive bladder cancer have worse oncological outcomes than younger patients. Some of this age disparity may be due to differences in tumour biology.

Persistent poverty and incidence-based melanoma mortality in Texas.

PURPOSE: Previous studies have shown that individuals living in areas with persistent poverty (PP) experience worse cancer outcomes compared to those living in areas with transient or no persistent poverty (nPP). The association between PP and melanoma outcomes remains unexplored. We hypothesized that melanoma patients living in PP counties (defined as counties with ≥ 20% of residents living at or below the federal poverty level for the past two decennial censuses) would exhibit higher rates of incidence-based melanoma mortality (IMM). METHODS: We used Texas Cancer Registry data to identify the patients diagnosed with invasive melanoma or melanoma in situ (stages 0 through 4) between 2000 and 2018 (n = 82,458). Each patient's PP status was determined by their county of residence at the time of diagnosis. RESULTS: After adjusting for demographic variables, logistic regression analyses revealed that melanoma patients in PP counties had statistically significant higher IMM compared to those in nPP counties (17.4% versus 11.3%) with an adjusted odds ratio of 1.35 (95% CI 1.25-1.47). CONCLUSION: These findings highlight the relationship between persistent poverty and incidence-based melanoma mortality rates, revealing that melanoma patients residing in counties with persistent poverty have higher melanoma-specific mortality compared to those residing in counties with transient or no poverty. This study further emphasizes the importance of considering area-specific socioeconomic characteristics when implementing place-based interventions to facilitate early melanoma diagnosis and improve melanoma treatment outcomes.

Robust global arrangement by coherent enhancement in Huygens-Fresnel traveling surface acoustic wave interference field.

The application of standing surface acoustic wave (SSAW) tweezers based on backpropagation superposition to achieve precise behavior manipulation of microscale cells and even nanoscale bacteria has been widely studied and industrialized. However, the structure requires multiple transducer components or full channel resonance. It is very challenging to design a simple structure for nano-control by complex acoustic field. In this study, a reflector-interdigital transducer (R-IDT) acoustofluidic device based on unilateral coherence enhancement is proposed to achieve SSAW definition features of periodic particle capture positions. The SAW device based on a unilateral transducer can not only generate leaky-SAW in water-filled microchannel, but also have a contribution of spherical waves in the vibration area of the substrate-liquid interface due to the Huygens-Fresnel diffractive principle. Both of them form a robust time-averaged spatial periodicity in the pressure potential gradient, accurately predicting the lateral spacing of these positions through acoustic patterning methods. Furthermore, a reflector based on Bragg-reflection is used to suppress backward transmitted SAW and enhance forward conducted SAW beams. By using a finite element model, R-IDT structure's amplitude enhances 60.78% compared to single IDT structure. The particle manipulation range of the diffractive acoustic field greatly improves, verified by experimental polystyrene microspheres. Besides, biocompatibility is conformed through red blood cells and Bacillus subtilis. We investigate the overall shift of periodic pressure field that can still occur when the phase changes. This work provides a simpler and low-cost solution for the application of acoustic tweezer in biological cell culture and filtering.

Hybrid Pressure Sensor Based on Carbon Nano-Onions and Hierarchical Microstructures with Synergistic Enhancement Mechanism for Multi-Parameter Sleep Monitoring.

With the existing pressure sensors, it is difficult to achieve the unification of wide pressure response range and high sensitivity. Furthermore, the preparation of pressure sensors with excellent performance for sleep health monitoring has become a research difficulty. In this paper, based on material and microstructure synergistic enhancement mechanism, a hybrid pressure sensor (HPS) integrating triboelectric pressure sensor (TPS) and piezoelectric pressure sensor (PPS) is proposed. For the TPS, a simple, low-cost, and structurally controllable microstructure preparation method is proposed in order to investigate the effect of carbon nano-onions (CNOs) and hierarchical composite microstructures on the electrical properties of CNOs@Ecoflex. The PPS is used to broaden the pressure response range and reduce the pressure detection limit of HPS. It has been experimentally demonstrated that the HPS has a high sensitivity of 2.46 V/104 Pa (50-600 kPa) and a wide response range of up to 1200 kPa. Moreover, the HPS has a low detection limit (10 kPa), a high stability (over 100,000 cycles), and a fast response time. The sleep monitoring system constructed based on HPS shows remarkable performance in breathing state recognition and sleeping posture supervisory control, which will exhibit enormous potential in areas such as sleep health monitoring and potential disease prediction.

Influence of treatment intensity and medical comorbidities in older adults with peripheral T cell lymphoma.

We conducted a population-based study of patients >65 years, diagnosed 2008-2017, with peripheral T-cell lymphoma (PTCL) using SEER-Medicare. Associations between PTCL subtype, treatment regimen, comorbidity, and mortality were assessed using the Kaplan-Meier method and multivariable Cox regression. Amongst the 2,546 patients, the median age was 77 years (interquartile range, 71-83). 5-year overall survival (OS) ranged from 22.2% to 37.3% depending on PTCL subtype. The most common frontline regimen was cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). 5-year OS rate was 47.0% for patients treated with etoposide + CHOP (N = 67; CHOEP), 33.7% for those treated with CHOP (N = 732), and 23.8% for patients treated with non-anthracycline-containing regimens (N = 105; p < 0.001). In patients without comorbidities, CHOEP remained independently associated with improved OS (HR 0.52, 95% CI,0.30-0.91). Median OS was 1.2 years from initiation of second-line therapy (N = 228) independent of treatment regimen. Frontline but not second-line treatment regimen is associated with OS in older patients with PTCL.

A novel comorbidity score for older adults with non-Hodgkin lymphoma: the 3-factor risk estimate scale.

For patients with non-Hodgkin lymphoma (NHL), formal comorbidity assessment is recommended but is rarely conducted in routine practice. A simple, validated measure of comorbidities that standardizes their assessment could improve adherence to guidelines. We previously constructed the 3-factor risk estimate scale (TRES) among patients with chronic lymphocytic leukemia (CLL). Here, we investigated TRES in multiple NHL subtypes. In the surveillance, epidemiology, and end results-Medicare database, patients with NHL diagnosed from 2008 to 2017 were included. Upper gastrointestinal, endocrine, and vascular comorbidities were identified using ICD-9/ICD-10 codes to assign TRES scores. Patient characteristic distributions were compared using χ2 or t test. Association of mortality and TRES score was assessed using Kaplan-Meier and multivariable Cox regression model for competing risk. A total of 40 486 patients were included in the study. Median age was 77 years (interquartile range [IQR], 71-83 years). The most frequent NHL subtypes were CLL (28.2%), diffuse large B-cell (27.6%), and follicular lymphoma (12.6%). Median follow-up was 33 months (IQR, 13-60 months). TRES was low, intermediate, and high in 40.8%, 37.0%, and 22.2% of patients, corresponding to median overall survival (OS) of 8.2, 5.3, and 2.9 years (P < .001), respectively. TRES was associated with OS in all NHL subtypes. In multivariable models, TRES was associated with inferior OS and NHL-specific survival. TRES is clinically translatable and associated with OS and lymphoma-specific survival in older adults with NHL.

Predictors of Emergency Room Visits After Ambulatory Breast Cancer Surgery in the Medicare Population.

BACKGROUND: Emergency department (ED) overuse is a large contributor to healthcare spending in the USA. We examined the rate of and risk factors for ED visits following outpatient breast cancer surgery. PATIENTS AND METHODS: Using linked data from the Surveillance, Epidemiology, and End Results (SEER) program and Medicare, we identified women who underwent curative breast cancer surgery between 2003 and 2015. Our outcome of interest was ED visits within 30 days of surgery. Multivariate regression was used to evaluate the odds of ED visit while controlling for clinical and socioeconomic variables. Secondary analyses assessed admission from the ED as well as costs. RESULTS: Of the 78,060 included patients, 5.1% returned to the ED, of which only 29.8% required hospital admission. Rate of ED visits increased with patient age. A higher percentage of Black patients returned to the ED compared with white patients (7.0% versus 5.0%, p < 0.001). Patients with higher income were less likely to visit the ED compared with those with lower income (OR 0.76, p < 0.001). Predictors of ED visits included: being unmarried (OR 1.18, p < 0.001), having stage 2 (OR 1.20, p < 0.001) or stage 3 cancer (OR 1.38, p < 0.001), and those with Charlson comorbidity score of 1 (OR 1.39, p < 0.001) or ≥ 2 (OR 2.29, p < 0.001). CONCLUSION: While a substantial number of patients return to the ED following outpatient breast surgery, most do not require hospital admission, which indicates that a large proportion of these visits could have been avoided. We identified several clinical and socioeconomic predictors of postoperative ED visits, which will aid in the development of patient risk profiling tools.

Competing mortality risk from second primary malignancy in bladder cancer patients following radical cystectomy: Implications for survivorship.

INTRODUCTION: Muscle-invasive bladder cancer (BC) often occurs in patients with competing mortality risks, while also being associated with the highest rate of second primary nonurothelial cancers (SNUC) of all solid malignancies. We investigated the incidence, risk factors, and timing of SNUC as a competing mortality risk factor in patients with BC who were treated with curative intent radical cystectomy (RC). METHODS: We performed a retrospective cohort study assessing patients who underwent RC for cT2-4 N0M0 BC from January 1, 2005 to December 31, 2018 at a single, high volume tertiary care referral center. The Fine-Gray multivariable regression model was used to evaluate predictive factors for SNUC. Cumulative incidence of mortality (CIM) was estimated with modified Kaplan-Meier analysis. RESULTS: The median follow-up time for the 693 patients who underwent RC was 3.7 years (interquartile range [IQR] 1.9-5.9 years). SNUC developed in 85 (12.3%) patients at a median 3.0 years post-RC (IQR 1.2-5.5 years). On multivariable analysis, the only significant predictor for developing SNUC was freedom from BC recurrence or metastasis (HR 1.54, 95% CI 1.12-1.76, P = 0.019). The most common SNUCs were primary lung cancer (24, 3.2% of cohort) and colon cancer (9, 1.3% of cohort). BC surveillance imaging diagnosed SNUC in 35/52 (67.3%) patients with solid-organ visceral primaries. The overall mortality rate for any SNUC was 38.8%, with the 3 most lethal cancer types being pancreatic, lung, and colon (62.5%, 54.2%, and 44.4% mortality, respectively). The incidence of SNUC uniformly increased postoperatively, with a cumulative incidence of 22.1% (95% CI, 16.8-27.9%) at 12-years post-RC. 163 patients (23.5%) died from BC, 33 patients (4.8%) died from SNUC, and 94 patients (13.6%) died from other causes. While the CIM for BC plateaued around 5-years post-RC at 24%, the incidence of other-cause mortality uniformly rose throughout the postoperative period. By post-RC year 9 there was no significant difference in CIM between BC (CIM 27.2%, 95% CI, 23.5-31.1%) and other-causes (CIM 20.0%, 95% CI, 15.8-24.6%). CONCLUSIONS: The cumulative incidence of SNUC at 12-years post-RC was 22%, with the majority identified on BC surveillance imaging. While BC mortality plateaued around 5-years post-RC, mortality related to SNUC or other causes rose steadily in the postoperative period. These data have clinical significance with regards to patient counseling, survivorship and oncologic surveillance in the highly comorbid muscle-invasive BC population.

Adjuvant 5-Fluorouracil/leucovorin, capecitabine, and oxaliplatin-related regimens for stage II/III colon cancer patients 66 years or older.

Adjuvant chemotherapy of leucovorin-modulated 5-fluorouracil (5-FU/LV), capecitabine, and adding oxaliplatin to 5-FU/LV or capecitabine (FLOX/OX) have been standard regimens for high-risk stage II or III colon cancer (CC). We aimed to evaluate their patterns of use, association with survival, and rate of emergency room visit (ER) or hospitalization during the treatment period. High-risk stage II or III patients aged >65 years diagnosed between 2007 and 2015, underwent colectomy, and received any of these three regimens were selected from SEER and Texas Cancer Registry (TC) linked with Medicare data. Chi-square test, Kaplan-Meier survival curves, Cox regression, and logistic regression were used in data analysis. A total of 5621 (1080 stage II and 4541 stage III) patients with median age of 72 years were included in this study. For stage II, 24.4% used 5-FU/LV, 31.2% used capecitabine, and 44.4% used FLOX/OX; the respective numbers for stage III were 13.8%, 17.9%, and 68.3%. Patients aged <70 years, not in the West region, not in Medicare state-buy-in program, and with no comorbidity were more likely to use FLOX/OX. FLOX/OX was associated with improved overall survival (OS) in stage II and III patients and improved cancer-specific survival in stage III patients compared with 5-FU/LV. The survival benefit of FLOX/OX was sustained in stage III patients aged ≥70 years. Capecitabine had the lowest ER/hospitalization rate with 19.2% in stage II and 28.9% in III. The use of FLOX/OX was associated with improved survival compared with 5-FU/LV among CC patients. Capecitabine was associated with the lowest ER/hospitalization rate.

Has COVID-19 Changed China's Digital Trade?-Implications for Health Economics.

Digital technologies have played a significant role in the defense against the COVID-19 pandemic. This development raises the question of whether digital technologies have helped Chinese exports recover quickly and even grow. To answer this question, we study monthly data on Chinese exports to 40 countries/regions from January 2019 to June 2020 and covering 97 product categories. The study takes the COVID-19 outbreak as a natural experiment and treats digital trade products as the treatment group. Using a generalized difference-in-differences (DID) approach, we empirically investigate how this major global public health crisis and digital trade have influenced Chinese exports. Our empirical analysis reveals that the COVID-19 pandemic has inhibited China's export trade overall, digital trade has significantly promoted trade, and the supply mechanism has played a significant role in promoting the recovery of exports. Heterogeneity tests on destination countries/regions reveal that digital trade has significantly promoted exports to countries/regions with different income levels, with a more significant effect on low-risk destinations than on high-risk destinations. The sector heterogeneity test demonstrates that digital trade has enhanced the export recovery of sectors dealing in necessities for pandemic prevention. Other robustness tests, including parallel trend and placebo tests, support the above conclusions. Finally, we extend the research conclusions and discuss their implication for health economics and the practice of fighting COVID-19.

Increased Incidence of Human Papillomavirus-Related Precancer or Second Malignancy Among Allogeneic Stem Cell Transplantation Patients: A SEER-Medicare Population Study.

Each year, more than 8000 allogeneic stem cell transplantations (allo-SCT) are performed in the United States, with approximately 30% of these patients age ≥60 years. Allo-SCT recipients are at increased risk for developing human papillomavirus (HPV)-related precancer or second malignancy. It is important to evaluate HPV-related precancer or second malignancy among allo-SCT recipients to develop or enhance screening and preventive practice guidelines to improve patients' survival and quality of life. In this retrospective matched case-control study, we estimated the cumulative incidence of HPV-related precancer or second malignancy in both male and female Medicare beneficiaries who underwent allo-SCT and compared it with the cumulative incidence in non-SCT controls and noncancer controls. Hematologic cancer patients age ≥18 years who underwent allo-SCT between 2002 and 2011 were matched 1:5 to non-SCT controls and to noncancer controls by age, sex, race/ethnicity, and duration of follow-up. Proportions of HPV-related precancer or second malignancy were estimated and compared between cases and controls using the chi-square test and logistic regression. Kaplan-Meier cumulative incidences were estimated and compared using log-rank tests. We identified 700 allo-SCT cases (median age, 64 years; median follow-up post-transplantation, 4.3 years) matched with 3159 non-SCT controls and 3302 noncancer controls. Approximately 3.7% of allo-SCT cases developed HPV-related precancer or second malignancy post-transplantation, compared with 1.9% of the non-SCT controls and 1.1% of the noncancer controls. The odds ratio of developing HPV-related precancer or second malignancy of allo-SCT cases compared with non-SCT controls and noncancer controls was 2.0 (95% confidence interval [CI], 1.25 to 3.18) and 3.5 (95% CI, 2.1 to 5.8), respectively. Both allo-SCT cases and non-SCT controls had significantly higher proportions and odds of developing HPV-related precancer or second malignancy compared with noncancer controls. The 5-year cumulative incidence in allo-SCT cases was 5%, compared with 2.1% in non-SCT controls and 1.2% in noncancer controls. The cumulative incidence of HPV-related precancer or second malignancy was statistically significantly higher in the allo-SCT than in either of the 2 matched control groups, and the non-SCT controls had a higher cumulative incidence of HPV-related precancer or second malignancy than the noncancer controls. The allo-SCT cases were at increased risk of developing HPV-related precancer or second malignancy compared with the non-SCT controls and noncancer controls. Routine screening of HPV-related precancer or second malignancy in allo-SCT recipients is needed to help prevent HPV-related precancer or second malignancy. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Prescription Patterns, Initiation, and 5-Year Adherence to Adjuvant Hormonal Therapy Among Commercially Insured Patients With Breast Cancer.

BACKGROUND: Tamoxifen and aromatase inhibitors (AIs) are used as adjuvant hormonal therapy (AHT) for early-stage hormone receptor-positive (HR+) breast cancer. Treatment for 5 years reduces cancer mortality by 30%. Despite this benefit, adherence to AHT has been suboptimal. Here, we evaluated AHT initiation and patient adherence in women with private health insurance. MATERIALS AND METHODS: Female patients with breast cancer ≥ 18 years of age who underwent mastectomy or lumpectomy between 1999 and 2015 were identified in the IBM MarketScan Research Database. AHT initiation and adherence rates were estimated for all AHT users regardless of HR+ status. Initiation rates were standardized using HR+ breast cancer incidence rates in the Surveillance, Epidemiology, and End Results (SEER) program. Adherence was defined as medication possession ratio ≥ 80%. Risk ratios, odds ratios, and their 95% CIs were calculated for factors associated with patients' initiation and adherence. RESULTS: Among 80,224 patients, the raw initiation rate was 71.8% and the standardized rate was 87.5%. We found 61.2% patients initiated treatment with AIs and 38.8% with tamoxifen. Patients' 1-year adherence rate was 84.4% and the 5-year rate was 65.2%. Prescription by mail-in order, using a single AHT regimen, 50 to 69 years of age, monthly out-of-pocket drug payment ≤ $11, in US dollars, no depression, no comorbidity, living in the Northeast, treatment in recent years, and receipt of a combination of chemotherapy, radiation, and surgery were associated with better adherence. CONCLUSION: Five-year AHT adherence rates are low among female patients with breast cancer with private health insurance. Effective approaches to improve AHT adherence are needed.

Treatment Sequences After Discontinuing a Tumor Necrosis Factor Inhibitor in Patients With Rheumatoid Arthritis: A Comparison of Cycling Versus Swapping Strategies.

OBJECTIVE: To evaluate the sequences of tumor necrosis factor inhibitors (TNFi) and non-TNFi used by rheumatoid arthritis (RA) patients whose initial TNFi therapy has failed, and to evaluate effectiveness and costs. METHODS: Using the Truven Health MarketScan Research database, we analyzed claims of commercially insured adult patients with RA who switched to their second biologic or targeted disease-modifying antirheumatic drug between January 2008 and December 2015. Our primary outcome was the frequency of treatment sequences. Our secondary outcomes were the time to therapy discontinuation, drug adherence, and drug and other health care costs. RESULTS: Among 10,442 RA patients identified, 36.5% swapped to a non-TNFi drug, most commonly abatacept (54.2%). The remaining 63.5% cycled to a second TNFi, most commonly adalimumab (41.2%). For subsequent switches of therapy, non-TNFi were more common. Patients who swapped to a non-TNFi were significantly older and had more comorbidities than those who cycled to a TNFi (P < 0.001). Survival analysis showed a longer time to discontinuation for non-TNFi than for TNFi (median 605 days compared with 489 days; P < 0.001) when used after initial TNFi discontinuation, but no difference in subsequent switches of therapy. Although non-TNFi were less expensive for adherent patients, cycling to a TNFi was associated with lower costs overall. CONCLUSION: Even though patients are more likely to cycle to a second TNFi than swap to a non-TNFi, those who swap to a non-TNFi are more likely to persist with the therapy. However, cycling to a TNFi is the less costly strategy.

Real-World Patterns of Everolimus Use in Patients with Metastatic Breast Cancer.

BACKGROUND: There is limited literature on patterns of everolimus use and subsequent hospitalizations and emergency room (ER) visits in real-world clinical practice. In this study, we describe patterns of everolimus use and hospitalizations and ER visits in a large cohort of patients with breast cancer (BC). MATERIALS AND METHODS: Patients with BC treated with everolimus were identified in the MarketScan database from 2009 to 2016. The pattern of everolimus use and frequency of associated ER visits and hospitalizations during treatment (between the first claim and 30 days after the last claim for everolimus) were identified. Descriptive statistics and regression models were used. RESULTS: A total of 3,556 everolimus users were identified (median age of 60 years; median days of use, 112). The initial prescribed dose was 10 mg in 74.8% of the patients. Compared with the initial dose, 23.5% of patients had a dose change. Forty-six percent of patients were hospitalized or had an ER visit during the treatment with everolimus. Age greater than 71, higher comorbidity score, treatment year prior to 2012, and lower initial dose were found to be significantly associated with ER visit/hospitalization in the regression models. CONCLUSIONS: A significant proportion of patients receiving everolimus had an ER visit or hospitalization during the use of everolimus. These results provide data regarding risks and benefits of treatment with everolimus. These results will be helpful in identifying patients at higher risk of hospitalizations or ER visits and facilitate evidence-based decision making to avoid serious complications. IMPLICATIONS FOR PRACTICE: Everolimus, a mammalian target of rapamycin inhibitor, is approved in combination with exemestane in patients with hormone receptor-positive tumors previously treated with anastrozole or letrozole. As new drugs become available, it is crucial to understand the adverse events and potential complications associated with the use of such drugs in the general population, outside of the controlled clinical trial setting. This study describes the patterns of everolimus use and adverse events, including hospitalization and emergency room visits, in a large cohort of patients with metastatic breast cancer in routine practice.

Interpenetrated Metal-Organic Frameworks with ftw Topology and Versatile Functions.

Through an "isoreticular expansion" strategy, a large number of highly porous zirconium-based metal-organic frameworks (Zr-MOFs) have been achieved using extended organic linkers in the past few years. However, interpenetrated Zr-MOFs with ftw topology have scarcely been reported, mainly owing to the used bulky tetratopic linkers that effectively prevent the network interpenetration. Here, we report a new family of zirconium and lanthanide (Ln) MOFs with ftw topology, constructed by hexanuclear Zr or Ln (Ln = Eu, Tb, Gd, Dy, Tm, Yb, Nd, and Er) clusters and a spirobifluorene-center tetracarboxylate linker. Our studies reveal that the isostructural Zr and Ln MOFs are all doubly interpenetrated with ultrahigh thermal and chemical stability. The observed unusual interpenetration can be attributed to the specific geometry of the spirobifluorene-center tetratopic linker. Gas adsorption studies show that the interpenetrated Zr-MOF is still highly porous and exhibits high performance for CO2 storage, which can be attributed to the strong CO2 binding environment contributed by the reduced pore size. In addition, the presented MOFs display strong characteristic luminescence in the UV-vis-NIR region. Moreover, the incorporation of the spiro-center linker into the framework can efficiently produce two-photon-excited photoluminescence with a large action cross-section value, which also benefited from the high packing density of the nonlinear optical chromophore linker in the interpenetrated structure.

Tuning the Connectivity, Rigidity, and Functionality of Two-Dimensional Zr-Based Metal-Organic Frameworks.

Presented herein is a group of highly stable Zr-based metal-organic frameworks with bowl-shaped dihydroanthracene-based tetratopic linkers as building blocks. Structural analysis reveals that these frameworks are all two-dimensional but comprise three distinct connectivities of Zr6 nodes. By using the steric hindrance of the nonplanar linker, the connectivity of Zr6 node can be tuned from 8-c to unusual 4-c. Further, through either one-pot synthesis or postsynthetic linker installation strategies, the connectivity of Zr6 node can be tuned from 8-c to 10-c by the insertion of a secondary linear dicarboxylate linker, from which not only the temperature-dependent flexibility of the structure can be effectively controlled with enhanced rigidity and thermal stability but also a scaffold for postsynthetic metalation of Pd(II) catalyst for Heck coupling reaction is offered.

Cost-Effectiveness Analysis of Hepatitis B Virus Screening and Management in Patients With Hematologic or Solid Malignancies Anticipating Immunosuppressive Cancer Therapy.

PURPOSE: National hepatitis B virus (HBV) screening recommendations for patients with cancer anticipating systemic anticancer therapy range from universal screening to screening based on risk of HBV infection, cancer therapy-specific risk of HBV reactivation, or both. We conducted cost-effectiveness analyses to identify optimal HBV screening strategies. PATIENTS AND METHODS: We constructed decision-analytic models to analyze three strategies (no screening, universal screening, and selective screening based on use of an HBV infection risk tool) for hypothetic cohorts of patients anticipating anticancer therapy at high or lower risk for HBV reactivation. Model parameters were drawn from previously published studies, the SEER-Medicare database, and other online resources. Outcomes included lifetime expected cost, quality-adjusted life expectancy, and incremental cost-effectiveness ratio, measured in US dollars required to gain an additional quality-adjusted life-year (QALY). RESULTS: For patients at high reactivation risk, universal screening dominated (ie, was cheaper and more effective than) the other two strategies. Universal screening was associated with a gain in life expectancy of 0.01 QALY compared with no screening and cost $76.06 less than no screening and $4.34 less than selective screening. For those at lower reactivation risk, universal screening still dominated selective screening; however, the incremental cost-effectiveness ratio of the universal screening strategy compared with no screening was $186,917 per QALY gained. CONCLUSION: Universal HBV screening is cost effective and cheaper for patients receiving anticancer therapy associated with a high reactivation risk. For patients receiving anticancer therapy associated with a lower reactivation risk, universal screening is not cost effective.

Kinesin-1 Regulates Extrasynaptic Targeting of NMDARs and Neuronal Vulnerability Toward Excitotoxicity.

N-methyl-D-aspartate (NMDA) receptor (NMDAR) is highly compartmentalized in neurons, and its dysfunction has been implicated in various neuropsychiatric and neurodegenerative disorders. Recent failure to exploit NMDAR antagonization as a potential therapeutic target has driven the need to identify molecular mechanisms that regulate NMDAR compartmentalization. Here, we report that the reduction of Kif5b, the heavy chain of kinesin-1, protected neurons against NMDA-induced excitotoxicity and ischemia-provoked neurodegeneration. Direct binding of kinesin-1 to the GluN2B cytoplasmic tails regulated the levels of NMDAR at extrasynaptic sites and the subsequent influx of calcium mediated by extrasynaptic NMDAR by regulating the insertion of NMDARs into neuronal surface. Transient increase of Kif5b restored the surface levels of NMDAR and the decreased neuronal susceptibility to NMDA-induced excitotoxicity. The expression of Kif5b was repressed in cerebral ischemia preconditioning. Our findings reveal that kinesin-1 regulates extrasynaptic NMDAR targeting and signaling, and the reduction of kinesin-1 could be exploited to defer neurodegeneration.