tbuckley/cabot-search huggingface dataset:
Association Between Broadband Internet Availability and Telemedicine Use
Authors: Andrew D. Wilcock, Sherri Rose, Alisa B. Busch, Haiden A. Huskamp, Lori Uscher-Pines, Bruce Landon, Ateev Mehrotra
Journal: JAMA Internal Medicine (2019)

Association Between Broadband Internet Availability and Telemedicine UseAccess to health specialists is difficult for many individuals in rural communities. 1Telemedicine, health care service delivered remotely through telecommunications, is one potential solution, but its use varies across regions, potentially associated with the availability of high-speed internet (broadband) access. 2 The Federal Communications Commission (FCC) and Congress have emphasized the need to increase broadband access in rural communities, in part to facilitate the use of telemedicine, and the FCC's Connect America Fund has set aside billions of dollars to subsidize broadband expansion. 3Our objective was to examine whether broadband availability in local communities is associated with telemedicine use.Methods | This study was approved by the Harvard Medical School Institutional Review Board, which waived the requirement for informed patient consent because of deidentified data.Per capita rates of telemedicine visits for each US county in 2016 were calculated using a nationally representative 20% sample of Medicare fee-for-service beneficiaries and data from Op-tumLabs Data Warehouse, a deidentified claims database for privately insured enrollees and Medicare Advantage enrollees in a large, private US health plan.Telemedicine visits were defined as health professional claims with either a telemedicine modifier (GT, GQ, 95) or a telemedicine-specific code (G0425-7, G0406-8, or G0459).Counts of visits were based on the beneficiary's county of residence.Because Medicare does not cover telemedicine for nonrural beneficiaries living in metropolitan counties, we did not include these beneficiaries in our per capita rates.We removed counties without rural residents, without both commercial and Medicare beneficiaries, and outlier counties in the top percentile of per capita telemedicine use.We measured broadband availability at the county level using the FCC's Fixed Broadband Deployment Data. 4 Broadband access was defined as the availability of wired internet download speeds of at least 25 megabytes per second and upload speeds of at least 3 megabytes per second. 5Counties were categorized based on the share of the county's population that could purchase broadband: low availability (0%-40%), medium availability (>40%-70%), or high availability (>70%).In each county, we also determined the number of census blocks targeted by the FCC's Connect America Fund.
Determination of the activated form of the progesterone receptor (PR) in endometrial cancer (EC).
Authors: Dinny Graham, Jacques Bosq, Jean-Michel Caillaud, Matthew A. Powell, Eric Leblanc, Keiichi Fujiwara, Thomas J. Herzog, Bradley J. Monk, Christine Clarke, Alexander A. Zukiwski, Erard M. Gilles, Robert L. Coleman
Journal: Journal of Clinical Oncology (2013)

5602 Background: Endocrine treatments, in general have limited clinical efficacy in endometrial cancer. Upon ligand binding, PRs in normal tissue form discrete focal subnuclear distribution patterns (FDP), which are associated with DNA transcription. FDP are indicative of functionally activated PRs (APRs), and are observed in EC, independently of menopausal status. The feasibility of using an IHC technique to characterize the PR functional status has previously been reported in breast cancer and the APR phenotype in cell lines correlates with anti-progestin activity. The goal of this study is to determine if APR can be identified in EC and to determine if this IHC technique &amp; APR phenotype could be developed as a companion diagnostic to predict anti-progestin efficacy in patients with EC. Methods: 72 archived primary EC specimens were processed with standard IHC for estrogen receptor (ER), PR &amp; proliferation (Ki67). APR status was determined using commercially available antibodies specific to the A and B isoforms of the PR (PRA and PRB) with standard microscopy at 1000x magnification. Results: 56 (78%) tumors were of endometrioid histology. Endometrioid tumors were ER + (68%) and PR + (84%). Two PR nuclear distribution patterns were observed: an aggregated pattern (A) which is indicative of APR and a diffuse or finely granular pattern (D) indicative of an inactivated PR. This resulted in three tumor phenotypes: A cells only, D cells only, and a mix of A + D cells. APR was defined as any tumor with more than 5% A cells. An average of 49% of tumor cells were positive with PRA, 35% were positive for PRB. APR was present with PR A in 41% and with PR B in 47% of the PR + endometrioid tumors. The APR status, for both PR A and PR B, was independent of PR positivity rate, PR staining intensity score and % Ki67 positive. APR pos phenotype was associated with a lower % ER pos staining. When observable, endometrial stromal and normal cells were PR positive (D pattern). Conclusions: APR can be identified using either PRA or PRB, in ~50 % of the EC samples; there was a pattern consistent with the presence of APR positive cells. The IHC technique to identify APR has the potential to be developed as companion diagnostic as a potential predictor of anti-progestin efficacy.
Safety, Clinical Activity, and Biological Correlates of Response in Patients with Metastatic Melanoma: Results from a Phase I Trial of Atezolizumab
Authors: Omid Hamid, Luciana Molinero, Christopher R. Bolen, Jeffrey A. Sosman, Eva Muñoz-Couselo, Harriet M. Kluger, David F. McDermott, John D. Powderly, Indrani Sarkar, Marcus Ballinger, Marcella Fassò, Carol O'Hear, Daniel S. Chen, Priti S. Hegde, F. Stephen Hodi
Journal: Clinical Cancer Research (2019)

Atezolizumab [anti-programmed death-ligand 1 (PD-L1)] selectively targets PD-L1 to block its interaction with receptors programmed death 1 and B7.1, thereby reinvigorating antitumor T-cell activity. We evaluated the long-term safety and activity of atezolizumab, along with biological correlates of clinical activity endpoints, in a cohort of patients with melanoma in an ongoing phase Ia study (NCT01375842).Patients with unresectable or metastatic melanoma were enrolled to receive atezolizumab 0.1 to 20 mg/kg or ≥10 mg/kg every 3 weeks. Primary study objectives were safety and tolerability. Secondary objectives included investigator-assessed efficacy measures; pharmacodynamic and predictive biomarkers of antitumor activity were explored.Forty-five patients were enrolled and were evaluable for safety. Most treatment-related adverse events (AE) were grade 1/2 (60%). Fatigue (44%), pruritus (20%), pyrexia (18%), and rash (18%) were the most common treatment-related AEs of any grade. No treatment-related deaths occurred. Overall response rate was 30% among 43 efficacy- evaluable patients, with a median duration of response of 62 months [95% CI, 35-not estimable (NE)]. Clinically meaningful long-term survival was observed, with a median overall survival of 23 months (95% CI, 9-66). Baseline biomarkers of tumor immunity [PD-L1 expression on immune cells, T effector (Teff), and antigen presentation gene signatures) and tumor mutational burden (TMB) were associated with improved response, progression-free survival, and overall survival.Atezolizumab was well tolerated, with durable responses and survival in patients with melanoma. PD-L1 expression, TMB, and Teff signatures may indicate improved benefit with atezolizumab in these patients.
Thromboembolic complications in cancer patients.
Authors: Gulsah Yenidunya, Hande Turna, Mehmet Akif Ozturk, Deniz Tural, Fatih Selcukbiricik, Ozcan Yildiz, Mustafa Ozguroglu, Fuat Demirelli, Evin Buyukunal, Suheyla Serdengecti
Journal: Journal of Clinical Oncology (2012)

e21143 Background: Thromboembolic events are frequent and important complications causing mortality and morbidity in cancer patients.To determine the charecteristics of these events can help us to determine the patients who have higher risks for thromboembolism. Methods: Characteristics of clinically or radiologically determined thromboembolic events were retrospectively analayzed from files of cancer patients followed up in the outpatient oncology clinic of Cerrahpasa Medical Faculty of Istanbul University. Results: A total of 267 thromboembolic events were analyzed.Events were encountered mostly in the venous system, only 3% were in the form of arterial embolism.Venous events were in the form of deep vein thrombosis (67%), pulmonary embolism (16.5%), vena cava superior thrombosis (2.6%), superficial migratory thrombophlebitis (0.4%) or two different forms occuring concomitantly(10.5%). Thromboembolism was determined most frequently in patients with gastrointestinal tumors (41.9%), lung cancer (22.1%) and gynecological tumors (12.1%). The most frequent histopathology was adenocarcinoma (72.4%).Thromboembolic complications were mostly in the form of lower extremity deep venous thrombosis in patients with gastointestinal, gynecological and urogenital tumors where as in the form of pulmonary embolism and vena cava superior thrombosis in patients with lung cancer. Nearly half of the patients with pulmonary embolism (%48.%) were asymptomatic and were diagnosed incidentally with radiological imaging. Upper extremity thrombosis were frequently encountered in patients with venous port a-cath system Most of the patients (87.7%) had metastatic cancer and were receiving chemotherapy (65.5% ) when the event occured. Cisplatin, 5–FU and gemcitabine were the most frequently used chemotherapy agents.Thromboembolic events related to cancer surgery occured usually (59%) in the first month after surgery.Recurrent thromboembolic events were determined in 8.9% of patients mostly whom had gastrointestnal primary tumors (54%). Conclusions: Characteristics of thromboembolic events can help to determine the patients who have higher risk for thromboembolism and predict types and time of the event and provide anticoagulation without delay.
Efficacy of EGFR plus TNF inhibition in a preclinical model of temozolomide-resistant glioblastoma
Authors: Gao Guo, Ke Gong, Vineshkumar Thidil Puliyappadamba, Nishah Panchani, Edward Pan, Bipasha Mukherjee, Ziba Damanwalla, Sabrina Bharia, Kimmo J Hatanpaa, David E Gerber, Bruce E Mickey, Toral R Patel, Jann N Sarkaria, Dawen Zhao, Sandeep Burma, Amyn A Habib
Journal: Neuro-Oncology (2019)

Glioblastoma (GBM) is the most common primary malignant adult brain tumor. Temozolomide (TMZ) is the standard of care and is most effective in GBMs that lack the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT). Moreover, even initially responsive tumors develop a secondary resistance to TMZ and become untreatable. Since aberrant epidermal growth factor receptor (EGFR) signaling is widespread in GBM, EGFR inhibition has been tried in multiple clinical trials without success. We recently reported that inhibiting EGFR leads to increased secretion of tumor necrosis factor (TNF) and activation of a survival pathway in GBM. Here, we compare the efficacy of TMZ versus EGFR plus TNF inhibition in an orthotopic mouse model of GBM.
Community and Hospital Factors Associated With Stroke Center Certification in the United States, 2009 to 2017
Authors: Yu-Chu Shen, Gabriel Chen, Renee Y. Hsia
Journal: JAMA Network Open (2019)

<h3>Importance</h3> The increased number of stroke centers in the United States may not be equitably distributed across all populations. Anecdotal reports suggest there may be differential proliferation in wealthier and urban communities. <h3>Objective</h3> To examine hospital characteristics and economic conditions of communities surrounding hospitals with and without stroke centers. <h3>Design, Setting, and Participants</h3> This cohort study included all general, short-term, acute hospitals in the continental United States and used merged data from the Joint Commission, Det Norske Veritas, Healthcare Facilities Accreditation Program, state health departments, the Centers for Medicare &amp; Medicaid Services, the American Hospital Association, the Dartmouth Atlas of Health Care, and the US Census Bureau from January 1, 2009, to September 30, 2017, to compare hospital and community characteristics of stroke-certified and non–stroke-certified hospitals and assessed characteristics of early and late adopters of stroke certification. <h3>Main Outcomes and Measures</h3> Stroke center certification was the primary outcome. Risk factors were grouped into 3 categories: economic and financial, hospital, and community characteristics. Survival analyses were performed using a Cox proportional hazards regression model. <h3>Results</h3> The study included 4546 US hospitals. During the study period, 1689 hospitals (37.2%) were stroke certified (961 adopted certification on or before January 1, 2009, 728 afterward). After controlling for other area and hospital characteristics, hospitals in low-income hospital service areas and the lower tertile of profit-margin distribution were less likely to adopt stroke certification (hazard ratio [HR], 0.62; 95% CI, 0.52-0.74 and HR, 0.87; 95% CI, 0.78-0.98, respectively). Urban hospitals had a higher likelihood of stroke certification than rural hospitals (HR, 12.79; 95% CI, 10.64-15.37). <h3>Conclusions and Relevance</h3> This study found that stroke centers have proliferated unevenly across geographic localities, where hospitals in high-income hospital service areas and with higher profit margins have a greater likelihood of being stroke certified. These findings suggest that market-driven factors may be associated with stroke center certification.
Cancer control in the Caribbean island countries and territories: some progress but the journey continues
Authors: Dingle Spence, Rachel Dyer, Glennis Andall-Brereton, Michael Barton, Susannah Stanway, M Austin Argentieri, Freddie Bray, Shamir Cawich, Sophia Edwards-Bennett, Christopher Fosker, Owen Gabriel, Natalie Greaves, Barrie Hanchard, James Hospedales, Silvana Luciani, Damali Martin, Marisa Nimrod, Camille Ragin, Donald Simeon, Guillermo Tortolero-Luna, Gilian Wharfe, Diana Sarfati
Journal: The Lancet Oncology (2019)
A randomized, double-blind, placebo-controlled phase III trial evaluating olanzapine 5 mg combined with standard antiemetic therapy for the prevention of chemotherapy-induced nausea and vomiting in patients receiving cisplatin-based chemotherapy: J-FORCE Study.
Authors: Hironobu Hashimoto, Masakazu Abe, Masahiko Nakao, Hideaki Mizutani, Yasuhiko Sakata, Yukiyoshi Fujita, Tomoyasu Nishimura, Katsuya Hirano, Hideaki Okada, Naoki Inui, Yukio Sakata, Hirotoshi Iihara, Sadamoto Zenda, Yosuke Uchitomi, Takuhiro Yamaguchi, Yukari Hoshina, Takako Yanai, Satoru Iwasa, Noboru Yamamoto, Yuichiro Ohe
Journal: Journal of Clinical Oncology (2019)

11503 Background: Olanzapine (OLZ) 10 mg added to standard antiemetic therapy including aprepitant (APR), palonosetron (PALO), and dexamethasone (DEX) has been recommended for the prevention of chemotherapy-induced nausea and vomiting (CINV) caused by highly emetogenic chemotherapy (HEC). Guidelines suggest that a dose of 5 mg should be taken into consideration in patients at risk of sedation. OLZ 5 mg showed an equivalent activity and favorable toxicity to somnolence in several phase II studies. We conducted a randomized, double-blind, placebo-controlled phase III trial to evaluate OLZ 5 mg in addition to standard antiemetic therapy for the prevention of CINV in patients receiving cisplatin-based chemotherapy. Methods: Patients receiving cisplatin (≥ 50 mg/m 2 ) were randomly assigned to either OLZ 5 mg or placebo on days 1–4, combined with APR, PALO and DEX. The primary endpoint was complete response (CR), defined as no vomiting and no rescue medications in the delayed phase (24–120 h). A total of 690 patients were required to detect a 10% increase in CR from 65% in the placebo to 75% in the OLZ, with a one-sided alpha of 2.5% and a power of 80%. Results: A total of 710 patients were enrolled (OLZ 356 and placebo 354). CR in the delayed phase was 79.1% (95% CI: 74.9–83.3) in the OLZ 5 mg and 65.8% (95% CI: 60.9–70.8) in the placebo ( p &lt; 0.001). Other efficacy results are summarized in Table. The most common treatment-related adverse events was somnolence (43.1% for OLZ vs. 33.0% for placebo). Conclusions: OLZ 5 mg combined with APR, PALO and DEX can be considered a new standard antiemetic therapy in patients receiving cisplatin-based chemotherapy. Clinical trial information: UMIN000024676. [Table: see text]
Efficacy and safety of peficitinib (ASP015K) in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase III randomised, double-blind, placebo-controlled trial (RAJ4) in Japan
Authors: Tsutomu Takeuchi, Yoshiya Tanaka, Sakae Tanaka, Atsushi Kawakami, Manabu Iwasaki, Kou Katayama, Mitsuhiro Rokuda, Hiroyuki Izutsu, Satoshi Ushijima, Yuichiro Kaneko, Teruaki Shiomi, Emi Yamada, Désirée van der Heijde
Journal: Annals of the Rheumatic Diseases (2019)

Objective To evaluate the efficacy and safety of the oral Janus kinase (JAK) inhibitor peficitinib versus placebo in Japanese patients with rheumatoid arthritis (RA). Methods In this multicentre, double-blind, parallel-group, placebo-controlled phase III study, patients with RA and inadequate response to methotrexate (MTX) were randomised 1:1:1 to placebo, peficitinib 100 mg once daily or peficitinib 150 mg once daily with MTX for 52 weeks. Based on baseline randomisation, at week 12, non-responders receiving placebo were switched to peficitinib until the end of treatment; the remaining patients were switched to peficitinib at week 28. Primary efficacy variables were American College of Rheumatology (ACR)20 response rate at week 12/early termination (ET) and change from baseline in van der Heijde-modified total Sharp score (mTSS) at week 28/ET. Results 519 patients were randomised and treated. Significantly more (p&lt;0.001) peficitinib (58.6%, 100 mg; 64.4%, 150 mg) than placebo (21.8%) recipients achieved ACR20 response at week 12/ET. Significantly lower (p&lt;0.001) mean changes from baseline in mTSS at week 28/ET occurred in peficitinib (1.62, 100 mg; 1.03, 150 mg) than placebo (3.37) recipients. Peficitinib was associated with haematological and biochemical parameter changes, and increased incidence of serious infections and herpes zoster-related disease. One death from suicide occurred in a patient in the placebo group after switching to peficitinib 100 mg. Conclusions In Japanese patients with RA and inadequate response to MTX, peficitinib demonstrated significant superiority versus placebo in reducing RA symptoms and suppressing joint destruction. Peficitinib had an acceptable safety and tolerability profile, with no new safety signals compared with other JAK inhibitors. Trial registration number NCT02305849 .
Nobiletin and its derivatives overcome multidrug resistance (MDR) in cancer: total synthesis and discovery of potent MDR reversal agents
Authors: Senling Feng, Huifang Zhou, Deyan Wu, Dechong Zheng, Biao Qu, Ruiming Liu, Chen Zhang, Zhe Li, Ying Xie, Hai-Bin Luo
Journal: Acta Pharmaceutica Sinica B (2019)

Our recent studies demonstrated that the natural product nobiletin (NOB) served as a promising multidrug resistance (MDR) reversal agent and improved the effectiveness of cancer chemotherapy in vitro. However, low aqueous solubility and difficulty in total synthesis limited its application as a therapeutic agent. To tackle these challenges, NOB was synthesized in a high yield by a concise route of six steps and fourteen derivatives were synthesized with remarkable solubility and efficacy. All the compounds showed improved sensitivity to paclitaxel (PTX) in P-glycoprotein (P-gp) overexpressing MDR cancer cells. Among them, compound 29d exhibited water solubility 280-fold higher than NOB. A drug-resistance A549/T xenograft model showed that 29d, at a dose of 50 mg/kg co-administered with PTX (15 mg/kg), inhibited tumor growth more effective than NOB and remarkably increased PTX concentration in the tumors via P-gp inhibition. Moreover, Western blot experiments revealed that 29d inhibited expression of NRF2, phosphorylated ERK and AKT in MDR cancer cells, thus implying 29d of multiple mechanisms to reverse MDR in lung cancer.
Preclinical identification of biomarkers of response to mTOR inhibitors and subsequent application in a phase II trial of sirolimus in pancreatic cancer patients refractory to gemcitabine
Authors: I. Garrido-Laguna, M. Rudek, A. Tan, M. Uson, C. Iacobuzio-Donahue, M. Angenendt, A. Jimeno, D. Laheru, M. Barret, M. Hidalgo
Journal: Journal of Clinical Oncology (2009)

4612 Background: Treatment for advanced pancreatic cancer refractory to gemcitabine has not been defined. We conducted an efficacy study in pancreatic cancer xenografts to identify biomarkers of response to mTOR inhibition and attempted to translate the results by conducting a phase II trial of sirolimus in this patient population. Methods: 19 direct pancreatic xenografts were treated with temsirolimus (20mg/Kg IP daily) for 28 days. Tumors were profiled with array CGH and gene expression arrays at baseline. TGI were calculated at 28 days. Patients refractory to gemcitabine were included in the clinical trial. Sirolimus was administered at 5mg/day for 28 days. Primary endpoint was 6 month survival rate (6mSR). Secondary endpoints included: baseline evaluation of AKT pathway activation, pharmacodynamic assessment of p-S6K in PBMC, pharmacokinetics and toxicity analysis. Results: In the preclinical study, mTOR sensitive tumors showed upregulation of genes involved in the renal cell cancer pathway. CGH identified focal gains in N-Ras and K-Ras and homozygous deletions of FHIT in sensitive cases. Overall, these genetic changes induced AKT pathway activation, and led us to explore high baseline p-S6K expression as a predictor of outcome in the clinical phase. Patient characteristics: Median age: 64 (39–77). 11 patients had received ≥ 2 prior lines of chemotherapy. 6mSR was 20%. 6mSR in the subgroup of patients who received rapamycin as first line chemotherapy after progression to gemcitabine was 34%. Baseline tumor p-S6K was not predictive for survival. Early pharmacodynamic changes in p-S6K in PBMC 6 hours after treatment initiation were correlated with survival (R 2 = 0.65). Treatment was well tolerated. The most common grade 3 adverse event was hyperglycemia in 10% of the patients. 7 (23%) patients achieved stable disease. Conclusions: Rapamycin is well tolerated in this setting. Early pharmacodynamic changes in p-S6K in PBMC were correlated with survival. Preclinical findings leading to activation of the AKT pathway in all sensitive cases warrants further validation studies. Efficacy data is limited by the selection of a heavily pretreated and poor prognosis population (DFS≤47 days). No significant financial relationships to disclose.