tbuckley/cabot-search huggingface dataset:
Comparative Efficacy and Safety of Oral P2Y <sub>12</sub> Inhibitors in Acute Coronary Syndrome
Authors: Eliano P. Navarese, Safi U. Khan, Michalina Kołodziejczak, Jacek Kubica, Sergio Buccheri, Christopher P. Cannon, Paul A. Gurbel, Stefano De Servi, Andrzej Budaj, Antonio Bartorelli, Daniela Trabattoni, E. Magnus Ohman, Lars Wallentin, Matthew T. Roe, Stefan James
Journal: Circulation (2020)

New randomized, controlled trials have become available on oral P2Y12 inhibitors in acute coronary syndrome. We aimed to evaluate current evidence comparing the efficacy and safety profile of prasugrel, ticagrelor, and clopidogrel in acute coronary syndrome by a meta-analysis of randomized controlled trials.We performed a network meta-analysis and direct pairwise comparison analysis of efficacy and safety outcomes from 12 randomized controlled trials including a total of 52 816 patients with acute coronary syndrome.In comparison with clopidogrel, ticagrelor significantly reduced cardiovascular mortality (hazard ratio [HR], 0.82 [95% CI, 0.72-0.92]) and all-cause mortality (HR, 0.83 [95% CI, 0.75-0.92]), whereas there was no statistically significant mortality reduction with prasugrel (HR, 0.90 [95% CI, 0.80-1.01] and HR, 0.92 [95% CI, 0.84-1.02], respectively). In comparison with each other, there were no significant differences in mortality (HR prasugrel versus ticagrelor, 1.10 [95% CI, 0.94-1.29] and 1.12 [95% CI, 0.98-1.28]). In comparison with clopidogrel, prasugrel reduced myocardial infarction (HR, 0.81 [95% CI, 0.67-0.98]), whereas ticagrelor showed no risk reduction (HR, 0.97 [95% CI, 0.78-1.22]). Differences between prasugrel and ticagrelor were not statistically significant. Stent thrombosis risk was significantly reduced by both ticagrelor and prasugrel versus clopidogrel (28%-50% range of reduction). In comparison with clopidogrel, both prasugrel (HR, 1.26 [95% CI, 1.01-1.56]) and ticagrelor (HR, 1.27 [95% CI, 1.04-1.55]) significantly increased major bleeding. There were no significant differences between prasugrel and ticagrelor for all outcomes explored.Prasugrel and ticagrelor reduced ischemic events and increased bleeding in comparison with clopidogrel. A significant mortality reduction was observed with ticagrelor only. There was no efficacy and safety difference between prasugrel and ticagrelor. Registration: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42019155648.
Construction of immune-related risk model for prognosis of hepatocellular carcinoma.
Authors: Yue Li, Ximing Xu
Journal: Journal of Clinical Oncology (2020)

e16683 Background: Hepatocellular carcinoma is the most common malignant tumor. Although the treatment of HCC has significantly improved, the 5-year survival rate is still only 18%. There is increasing evidence that tumor immune microenvironment (TIM) plays critical roles during cancer initiation and progression. Based on the comprehensive exploration of the immunogenomic, an immune-related risk model was constructed to predict hepatocellular carcinoma prognosis. Methods: Transcriptomic data of HCC patients were downloaded from the TCGA database, and the differentially expressed immune-related genes (IRGs) (FDR &lt; 0.01, |log2fold change| &gt; 2) were identified. Functional enrichment analysis was performed to explore potential molecular mechanisms of the differentially expressed IRGs. By univariate and multivariate Cox regression analysis, we identified eight prognosis-related IRGs. Based on the expression levels of IRGs, we constructed the immune-related risk model. The Kaplan‐Meier (K‐M) survival curves, ROC curves, univariate and multivariate analysis were used to evaluate the immune-related risk model. According to the risk score, HCC patients were stratified into low and high-risk groups. CIBERSORT was applied to analyze the profiling difference of infiltrating immune cells between the two groups. Results: A total of 113 differentially expressed IRGs were identified, of which nine IRGs were correlated with the prognosis of HCC patients. Functional enrichment analysis showed that these genes were involved in immune response and immune signal pathway. The immune-related risk model consisted of eight IRGs (FABP6, RBP2, MAPT, BIRC5, PLXNA3, CSPG5, IL17D and STC2). The immune risk score was an independent prognostic factor (HR, 2.63 [1.93−3.58]; P = 8.16E −10 ) and the patients with a high-risk score tended to have a shorter OS than those with a low-risk score. In the TCGA cohort, high-risk patients tended to have an advanced stage. Moreover, we found that the patients in the high-risk group had higher fractions of T follicular cells helper and macrophages M0. The patients with low-risk scores had higher fractions of CD 8+ T cells and CD 4+ T cells. Conclusions: We have identified the immune-related risk model of hepatocellular carcinoma based on the expression profiles of eight immune-related genes. This model could predict prognosis and reflect the tumor immune microenvironment of HCC patients, which can provide new insights in the individualized treatment of HCC and potential novel targets for immunotherapy.
A randomized phase III trial of adjuvant chemotherapy versus concurrent chemoradiotherapy (CCRT) for postoperative cervical cancer: Japanese Gynecologic Oncology Group study (JGOG1082).
Authors: Akiko Furusawa, Munetaka Takekuma, Tomoka Usami, Eiji Kondo, Shin Nishio, Koji Nishino, Yuichiro Miyamoto, Ryoichi Yoshimura, Miho Watanabe, Mikio Mikami, Takayuki Enomoto
Journal: Journal of Clinical Oncology (2020)

TPS6094 Background: Cervical cancer is one of the common gynecologic cancer and the incidence of invasive cervical cancer has increased over the past few decades, particularly in younger women. The standard treatment for stage IB to IIB cervical cancer is a radical hysterectomy. In Japan, more than 80% of institutions, radical hysterectomy is chosen as the primary treatment for patients with stage IB1 and IIA1 cervical cancer. Patients with high-risk factors would be recommend adjuvant concurrent chemoradiotherapy (CCRT). However, adjuvant CCRT might not reduce distant metastasis and might cause of severe gastrointestinal and urinal toxicity. To avoid those adverse events of adjuvant CCRT, many Japanese gynecologic oncologists perform chemotherapy as adjuvant therapy. In the first multi-institutional phase II trial conducted in stage IB-IIA cervical cancer with pelvic lymph node metastasis (JGOG1067), we found a 5-years disease free-survival rate of 86.5%, suggesting the adjuvant chemotherapy had promising efficacy and would be feasible for a long time. No prospective study reported that adjuvant chemotherapy would improve overall survival in patients with the high-risk cervical cancer. Methods: High risk stage IB-IIB cervical cancer patients who underwent radical hysterectomy are eligible for the study. Patients with high risk are defined as those with pelvic lymph-node metastasis and/or parametrial invasion. Patents with SCC, adenocarcinoma, adenosquamous cell carcinoma are eligible for the study. After providing informed consent, patients are randomized on a 1:1 basis to receive CCRT or chemotherapy. Randomization is stratified by the faculty, FIGO stage, and pathological subtype (SCC or non-SCC). Treatment have to be started within 6 weeks after surgery. CCRT group is given whole pelvis irradiation 50.4Gy and cisplatin (40mg/m 2 /week). Chemotherapy group is given paclitaxel (175mg/m 2 ) plus cisplatin (50mg/m 2 ) or paclitaxel (175mg/m 2 ) plus carboplatin(AUC of 6). The primary endpoint is overall survival (OS). Secondary endpoints are disease free survival (DFS), adverse events and QOL. This study began in November 2019 and a total of 290 patients will be accrued within 5 years. The study is coordinated by of the JGOG cervical cancer committee. Clinical trial information: 041190042.
M-palliative care link: Improving symptom control and information exchange among specialists and local health workers treating late-STAGE Tanzanian cancer patients.
Authors: Susan Miesfeldt, Twalib Athumani Ngoma, Beatrice Mushi, Mamsau Ngoma, Habiba Mahuna, Robert Morse, Yun Xian Ho, Erin Quinn, Kaley Xian Lambden, Sarah Sagan, Joshua Mmari, Elia Mmbaga, Frances L Lucas
Journal: Journal of Clinical Oncology (2020)

e24146 Background: Lack of effective end-of-life symptom control among late-stage cancer patients is a Tanzanian public health priority, calling for innovative community-based solutions. Mobile health technology holds promise; however, existing resources are limited and access to palliative care specialists is poor. This work aimed to develop a secure mobile-/web-based symptom assessment/control communication system (m-Palliative Care Link; mPCL) that extends access to a limited number of palliative care specialists (hereafter, specialists). mPCL is based on the existing patient-focused African Palliative care Outcome Scale (POS), adapted for mobile symptom assessment, and is designed to support end-of-life care coordination among specialists, patients/caregivers, and local health workers (LHWs) (i.e., user groups). Methods: In partnership with Tanzanian specialists, mPCL was developed following a user-centered design process. mPCL prototype usability testing was conducted with 5-7 participants per user group and included a combination of hands-on observations as well as collection of feedback on ease-of-use and recommendations for modifications. User input was incorporated into the mPCL prototype iteration, tested via field study with 45 late-stage cancer patients discharged from Ocean Road Cancer Institute in Dar es Salaam. A brief mPCL usability/utility survey, including closed- and open-ended survey items, was conducted with field study participants from user groups at six weeks. Results: Prototype usability test participants successfully used the application and indicated that it would be very helpful. Recommendations from usability testing included redesign data collection tools, simplify patient/caregiver application, and broaden clinical data access. Six-week field study survey data showed that a significant majority (range: 68-100%) of specialists and patients “definitely agreed” that mPCL improved patient-provider communication, symptom-based care, care access, both quality of life and care, and reduced need for travel. Nearly all specialists and patients (93% and 98%, respectively) reported that mPCL was easy to use. Conclusions: mPCL promises to assess and address the symptom-control needs of late-stage cancer patients. Due to its reliance on existing technology/personnel, mPCL should be sustainable and scalable among cancer patients and those with other chronic diseases in low resource settings.
Primary analysis of a randomized, double-blind, phase II study of the anti-TIGIT antibody tiragolumab (tira) plus atezolizumab (atezo) versus placebo plus atezo as first-line (1L) treatment in patients with PD-L1-selected NSCLC (CITYSCAPE).
Authors: Delvys Rodriguez-Abreu, Melissa Lynne Johnson, Maen A. Hussein, Manuel Cobo, Anjan Jayantilal Patel, Nevena Milica Secen, Ki Hyeong Lee, Bartomeu Massuti, Sandrine Hiret, James Chih-Hsin Yang, Fabrice Barlesi, Dae Ho Lee, Luis G. Paz-Ares, Robert Wenchen Hsieh, Karen Miller, Namrata Patil, Patrick Twomey, Amy V. Kapp, Raymond Meng, Byoung Chul Cho
Journal: Journal of Clinical Oncology (2020)

9503 Background: The immunomodulatory receptor TIGIT is a novel inhibitory immune checkpoint present on activated T cells and NK cells in multiple cancers, including NSCLC. In a phase I study (GO30103), co-inhibition of TIGIT and PD-L1 signaling with tira plus atezo in CIT-naïve PD-L1 positive NSCLC potentially improved overall response rates (ORR) compared to historical ORR with PD-L1/PD-1 inhibitors. We conducted this phase II trial to confirm the efficacy and safety of tira plus atezo (TA) compared to placebo plus atezo (PA) in 1L NSCLC (GO40290, NCT NCT03563716). Methods: This prospective, randomized, double-blind, placebo-controlled trial enrolled patients (pts) with chemotherapy-naïve PD-L1+ (TPS ≥ 1% by 22C3 IHC pharmDx Dako assay) locally advanced or metastatic NSCLC with measurable disease, ECOG PS 0-1, and without EGFR or ALK alterations. Pts were randomized 1:1 to TA (tira 600 mg IV plus atezo 1200 mg IV) or PA (placebo plus atezo 1200 mg IV) on day 1 of every 3-week cycle. Stratification factors were PD-L1 status (TPS ≥ 50% vs TPS 1-49%), histology, and tobacco history. Co-primary endpoints were investigator assessed ORR and PFS, and additional endpoints were duration of response (DOR), OS, and safety. Exploratory endpoints were the effect of PD-L1 status on ORR and PFS. Results: 135 pts were randomized to PA (n = 68) or TA (n = 67). At primary analysis (30 Jun 2019), TA improved ORR and median PFS (mPFS) compared to PA, with median follow-up of 5.9 mo. In the safety population (68 in PA, 67 in TA), treatment-related AEs (TRAEs) occurred in 72% (PA) and 80.6% (TA); Grade ≥3 TRAEs occurred in 19.1% (PA) and 14.9% (TA). AEs leading to treatment withdrawal occurred in 10.3% (PA) and 7.5% (TA). Clinical trial information: NCT03563716 . With an additional six months of follow-up since the primary analysis (2 Dec 2019, median follow-up of 10.9 mo), improvement in ORR and mPFS was maintained in ITT for TA (37.3% [25.0, 49.6] and 5.6 mo [4.2, 10.4]) vs PA (20.6% [10.2, 30.9] and 3.9 mo [2.7, 4.5]). The safety profile remained tolerable. Conclusions: Treatment with TA compared to PA showed clinically meaningful improvement in ORR and PFS in ITT. The safety profile of TA was similar to PA. [Table: see text]
社区高血压患者自我管理项目定性评价
Authors: 叶文, 于普林, 刘雪荣, 刘耀军, 张静, 白筱玲, 乌正赉
Journal: BMJ (2004)

慢性病自我管理方法是强调患者自身在管理所患慢性病方面的责任和潜能、改善患者健康状况和生活质量、减少卫生服务利用的有效办法[1].借鉴美国斯坦福大学创建的慢性病自我管理健康教育项目和上海慢性病自我管理项目的成功经验,我们于2002年1月～12月在河北省三河市燕郊开发区实施了高血压自我管理项目.为了解此项目的效果和可接受性,我们收集项目实施4个月后参加者的意见和建议,并对该项目进行了定性评价。
Fragility index of trials supporting approval of anti-cancer drugs in common solid tumors.
Authors: Alexandra Desnoyers, Michelle Nadler, Ramy Saleh, Eitan Amir
Journal: Journal of Clinical Oncology (2020)

2055 Background: The Fragility Index (FI) quantifies the reliability of positive trials by estimating the number of events which would change statistically significant results to non-significant results. Here, we calculate the FI of trials supporting approval of drugs for common solid tumors. Methods: We searched Drugs@FDA to identify randomized trials (RCT) supporting drug approvals by the US Food and Drug Administration between January 2009 and December 2019 in lung, breast, prostate, gastric and colon cancers. We adapted the FI framework (Walsh et al. J Clin Epidemiol 2014) to allow use of time to event data. First, we reconstructed survival tables from reported data using the Parmar Toolkit (Parmar et al. Stat Med 1998) and then calculated the number of events which would result in a non-significant effect for the primary endpoint of each trial. The FI was then compared quantitatively to the number of patients in each trial who withdrew consent or were lost to follow-up. Multivariable linear regression was used to explore association between RCT characteristics and the FI. Results: We identified 69 RCT with a median of 669 patients (range 123-4804) and 358 primary outcome events (range 56-884). The median FI was 26 (range 1-322). The FI was ≤10 in 21 trials (30%) and ≤20 in 31 trials (45%). Among the 69 RCT, the median number of patients who withdrew consent or were lost to follow up was 27 (range, 6-317). The number of patients who withdrew consent or were lost to follow-up was equal or greater than the FI in 42 trials (61%). There was statistically significant inverse association between FI and trial hazard ratio (p0,001) and a positive association with number of patients who were lost to follow-up or withdrew consent (p0,001). There was no association between trial sample size, year of approval or reported p-value and the FI. Conclusions: Statistical significance of trials supporting drug approval in common solid tumors relies often on a small number of events. In most trials the FI was lower than the number of patients lost to follow up or withdrawing consent. Post-approval randomized trials or real-world data analyses should be performed to ensure that effects observed in registration trials are robust.
以脊髓病变为首发症状的主动脉夹层一例
Authors: 郭福玲, 何伟
Journal: BMJ (2011)

患者男,48岁,以“双下肢无力、麻木伴尿便障碍10 d”为主诉于2011年1月20日入院.10 d前劳累及着凉后安静状态下突发前胸、腹部、后背部撕裂样剧痛,继而出现双下肢无力、麻木及尿便障碍.病前无感染、外伤史.门诊以“脊髓病变”收入神经内科.既往高血压病史10余年,血压最高160/110 mm Hg(1 mm Hg=0.133 kPa),未规律用药.支气管哮喘病史20余年,未系统治疗.吸烟史20余年,20支/d. 关键词：动脉瘤;夹层
Chronic venous diseases of lower extremities: diagnosis, treatment and primary care
Authors: Yan Song
Journal: BMJ (2019)

下肢慢性静脉疾病（CVD）是指因静脉的结构或功能异常而使静脉血回流不畅、静脉压力过高导致的一系列症状和体征为特征的综合征，主要包括慢性静脉功能不全、深静脉血栓形成后综合征、髂静脉病变，临床表现以下肢沉重、酸胀、疼痛、水肿、静脉曲张、皮肤状态改变和静脉溃疡等为主。随年龄增加发病率逐步上升，给患者的工作和生活造成严重影响，早期明确诊断以及积极预防治疗尤为重要。
Gls-010, a novel anti-PD-1 mAb in Chinese patients with recurrent or metastatic cervical cancer: Results from a multicenter, open-label and single-arm phase II trial.
Authors: Xiaohua Wu, Lingfang Xia, Qi Zhou, Jianqing Zhu, Ke Wang, Jie Chen, Yi Huang, Gulina Kurb, Baoping Chang, Weidong Zhao, Xia Wang, Yingjie Yang, Zhongqiu Lin, Xiaoyong Luo, Ge Lou, Chunyan Wang, Jing Wang, Haijin Meng
Journal: Journal of Clinical Oncology (2020)

6032 Background: GLS-010 is a novel fully human anti-PD-1 mAb. Previous Phase I study exhibited favorable result of tolerance, preliminary efficacy and 240mg fixed dose q2w was selected as Recommended Phase II Dose (RP2D). This Phase II clinical trial is aimed to further evaluate the safety and anti-tumor activity of GLS-010 in patients with recurrent or metastatic cervical cancer. Methods: PD-L1 positive (combined positive score (CPS) ≥1) patients with recurrent or metastatic cervical cancer who had received one or more lines of chemotherapy were enrolled and received GLS-010 240mg every 2 weeks. Primary endpoint was the objective response rate (ORR) per RECIST 1.1, secondary endpoints included duration of response (DoR) and safety. Results: From May 16 th 2019 to December 24 th 2019, 44 pts were enrolled and treated in the study. As of December 24 th 2019,the median line of prior systemic chemotherapy was 2(range: 1~4), and 59% (26/44) of pts had received ≥2 previous lines of chemotherapy. The median number of GLS-010 doses was 1.5(range: 1~4). 25 pts received response evaluation per investigator review. With a median follow-up of 2.9 months, 7 of 25 evaluable pts achieved a partial response (PR). The ORR was 28% (95% CI, 12.07-49.39), with 7 pts achieving a PR ( 3 of 7 confirmed), 3 pts achieving stable disease (SD) and 15 pts with progressive disease (PD), 1 of which was assessed as dissociated response with treatment ongoing. Median duration of response had not been reached yet. 33 of 44 patients (75%) experienced one or more treatment-related adverse events (TRAEs) per NCI CTCAE v4.03, most of which were grade 1 or 2. The most common TRAEs were Anaemia (15/44), and 73.3% of them were grade 1 or 2. The most common ≥grade 3 TRAE included Anaemia (4/44). As data cut off, only 1 pt discontinued treatment due to adverse event. Conclusions: GLS-010 showed impressive therapeutic activity and manageable safety profile in Chinese recurrent or metastatic cervical cancer patients. Current evidence support further development of GLS-010 in this and more indications. This trial is still ongoing, and we are looking forward to further results. Clinical trial information: NCT03972722.
Real-world treatment patterns among metastatic breast cancer patients by BRCA status and phenotype.
Authors: Wendy Sebby, Alexander Liede, Debasish Mazumder, Anirban Ghosh, Eros Papademetriou, Ravi C. Potluri, Bruce Allen Bach, Jerzy Edward Tyczynski
Journal: Journal of Clinical Oncology (2020)

e13046 Background: BRCA1/2 mutations account for 5-10% of breast cancer (BC) patients. BRCA1 mutations are associated with aggressive tumors, often triple negative (TNBC) (HER2, estrogen-receptor [ER], progesterone-receptor [PR] negative) and are mainly treated with combination chemotherapy or platinum agents. This study aimed to compare real world treatment patterns in breast cancer patients who were BRCA-mutation positive (BRCA+) and those who were BRCA-mutation negative (BRCA-), focusing on hormone-receptor positive (HR+) and TNBC subgroups. Methods: Optum’s Humedica electronic health records (EHR) database was used to identify a cohort of women with 1) confirmed BC ICD-9/ICD-10 diagnosis between 2008 and 2018, 2) at least 12 months of history in EHR, 3) at least one distant metastasis diagnosis (per ICD-9/ICD-10 or physician notes), and 4) no previous diagnosis of other primary cancers in previous 12 months. HR and HER2 test results were used to create relevant subgroups. Distinct lines of therapy (LOT) in the post-metastatic period were established using business rules. Treatment patterns and duration of treatment were analyzed. Results: Among 65,934 metastatic BC patients identified, 7941 were BRCA+, of whom 5366 (68%) were HR+ and 1323 (17%) had TNBC phenotype, while 4027 were BRCA-, of whom 2859 (71%) were HR+ and 561 (14%) had TNBC phenotype. Seventy-one percent of BRCA+ women underwent drug treatment, compared to 65% of BRCA- women. Drug treatments included hormonal treatment (+/-other agents), targeted therapy, and chemotherapy only, and varied across the different cohorts (Table). Mean (median) duration of treatment in LOT1 in the BRCA+ and BRCA- cohorts was 117 (73) and 117 (72) days, respectively. Conclusions: Real-world evidence on treatment patterns in BC patients revealed substantial differences across important biomarker and hormonal status BC phenotypes. As a preponderance of women with TNBC are still being treated exclusively with chemotherapy, these data highlight how the need for development of effective treatment options for TNBC remains high. [Table: see text]