tbuckley/cabot-search huggingface dataset:
CTEP 9557: A dose-escalation trial of combination dabrafenib, trametinib, and AT13387 in patients with BRAF mutant solid tumors.
Authors: Meghan Mooradian, James M. Cleary, Justine Vanessa Cohen, Donald P. Lawrence, Elizabeth Iannotti Buchbinder, Anita Giobbie-Hurder, Aparna Raj Parikh, Geoffrey Shapiro, Lancia Darville, Keiran Smalley, John M Koomen, Amber Newton, Harold N. Keer, S. Percy Ivy, Helen X. Chen, Ryan J. Sullivan
Journal: Journal of Clinical Oncology (2020)

3609 Background: Combination BRAF and MEK inhibitor therapy is associated with response in patients (pts) with BRAF mutant (mut) solid tumors; however critical limitations for the durable activity of these agents remains. Preclinically, the addition of heat shock protein 90 (HSP90) inhibitors improves the efficacy of BRAF inhibitor (BRAFi) therapy in both BRAFi -sensitive and resistant mutant cell lines. Methods: CTEP study 9557 (NCT02097225) is a phase I study designed to determine the safety and efficacy of the small molecule HSP90inhibitor, AT13387, in combination with dabrafenib (dab) and trametinib (tram) in patients with BRAF V600E/K mut solid tumors. Prior chemotherapy, immunotherapy, BRAF and/or MEK exposure was permitted. The primary objective was to determine the maximum tolerated dose (MTD). Results: From July 2015 to June 2018, 22 patients with previously treated, metastatic BRAF V600E/K mut solid tumors were enrolled using a 3 + 3 design at four dose levels (DL) (Table). Pts were predominantly female (59%) with a median age of 57.5yrs (37 -75). The most common tumor type was BRAF V600E mut colon cancer (N=12). Dose limiting toxicities (DLTs) occurred in one patient in DL3 and one in DL4, specifically grade 3 myelosuppression and fatigue, respectively. The MTD was Dab 150mg [BID/PO], Tram 2mg [QD/PO] and AT1187 260mg/m2 [D1,8,15/IV]. Twenty-one of 22 pts were eligible for efficacy assessment. Best response, per RECIST 1.1, was partial response (PR) in 2 pts – one with colon ca (TKI-naïve), one with melanoma (TKI-resistant) - stable disease (SD) in 8 pts, and disease progression (PD) in 11 with a disease control rate (PR + SD) of 47.6% (90% CI: 29% - 67%). Median time to progression was significantly longer in DL3 (3.9 mths; 1.8-9.2) compared to DL1 (1.6mths; 0.9-1.7) or DL2 (1.5; 0.6-3.6). Median PFS and OS were 1.8mths (90% CI: 1.6 – 3.7mths) and 5.1 mths (90% CI: 2.5 -10.6mths), respectively. Median OS was not reached in DL3/4. Correlative data on the expression of the key signaling proteins relating to response will be presented at the meeting. Conclusions: HSP90 inhibition combined with BRAF/MEK inhibition was determined to be safe with evidence of disease control in a heavily pre-treated population of pts with BRAF V600E/K mut solid tumors. Clinical trial information: NCT02097225 . [Table: see text]
Ipsilateral invasive cancer risk after diagnosis with ductal carcinoma in situ (DCIS): Comparison of patients with and without index surgery.
Authors: Marc D Ryser, Laura Hendrix, Samantha M. Thomas, Thomas Lynch, Anne McCarthy, Zahed Mohammed, Amanda B. Francescatti, Elizabeth S. Frank, Ann H. Partridge, Alastair Mark Thompson, Terry Hyslop, Eun-Sil Shelley Hwang
Journal: Journal of Clinical Oncology (2020)

519 Background: Most women diagnosed with ductal carcinoma in situ (DCIS) undergo surgical resection, potentially leading to overtreatment of patients who would not develop clinically significant breast cancer in the absence of locoregional treatment. We compared the risk of ipsilateral invasive breast cancer (iIBC) between DCIS patients who received breast conserving surgery (BCS) for their index diagnosis of DCIS (BCS group) and patients who did not receive any locoregional treatment within 6 months of diagnosis (surveillance [SV] group). Methods: A treatment-stratified random sample of patients diagnosed with screen-detected and biopsy-confirmed DCIS in 2008-14 was selected from 1,330 Commission on Cancer-accredited facilities (20/site). Excluding patients who received a mastectomy ≤6 months, the final analytic cohort contained 14,245 (88.2%) BCS and 1,914 (11.8%) SV patients. Subsequent breast events were abstracted up to 10 years after diagnosis. Primary outcome was the 8-year absolute difference in iIBC risk between BCS and SV; a subgroup analysis was performed for grade I/II patients. A propensity score (PS) model for treatment was fitted with sampling design (SD) weighting and random effects for patients within facilities. Absolute risk differences were estimated using PS-SD-weighted Kaplan Meier estimators. Results: Overall, median age at diagnosis was 61 years (IQR: 52-69) and median follow-up was 5.8 years (95% CI 5.7-6.1). The majority of patients were Caucasian (81.9%), with estrogen receptor-positive (80.6%), and nuclear grade I/II (54.5%) DCIS. The fraction of patients with a Charlson comorbidity score of ≥2 was higher in SV (14.2%) compared to BCS (6.4%, p &lt; 0.001). The 8-year risk of iIBC was 3.0% (95% CI: 2.4%-3.6%) for BCS and 7.7% (95% CI: 4.9%-10.5%) for SV, with an absolute risk difference of 4.7% (95% CI: 4.5%-4.9%; log-rank p &lt; 0.001). Among patients with grade I/II tumors, the 8-year risk of iIBC was 3.1% (95% CI: 2.3%-4.0%) for BCS and 6.1% (95% CI: 2.5%-9.8%) for SV; difference: 3.0% (95% CI: 2.7%-3.2%; p = 0.005). Conclusions: Despite an increased risk of iIBC in SV patients compared to BCS patients, the 8-year risk did not exceed 10% in either group. The risk of recurrence in BCS patients was comparable to previously reported estimates. These data demonstrate a considerable degree of overtreatment among patients with non-high grade DCIS. Prospective clinical trials will help determine the tradeoffs between universally directed as opposed to selectively applied surgery for low risk DCIS.
Delay discounting as a predictor of adjuvant endocrine therapy adherence among breast cancer survivors.
Authors: Jennifer Vaughn, Chesley Ammerman, Jeffrey Stein
Journal: Journal of Clinical Oncology (2020)

e24172 Background: Despite the demonstrated mortality benefit, 30-70% of hormone-responsive breast cancer (BC) survivors struggle to adhere to adjuvant endocrine therapy (ET). Little is known about patient-specific behavioral traits and their role in ET non-adherence. To gain a survival benefit, patients must adhere to ET for years. In contrast, the benefits of discontinuing ET (i.e., avoiding toxicity) are immediate. Thus, adherence requires one’s behavior to be guided by future outcomes, rather than immediate gratification. We therefore hypothesized that ET adherence may be related to the behavioral economic process of delay discounting (DD; i.e. devaluation of delayed outcomes), which provides a measure of how individuals value the future. Methods: BC survivors (age 18-80) prescribed adjuvant ET within the last 5 years were recruited. ET adherence was measured by pill count and self-report. DD was measured using two methods: monetary DD was measured using a validated task in which participants made repeated, hypothetical choices between a larger amount ($100 or $1000) available after a time delay or half of this amount ($50 or $500) available now. Across trials, the delay to the larger amount is titrated based on previous choices until reaching a delay at which the participant becomes indifferent to waiting for the larger reward. Cancer DD was measured using an investigational task adapted from the adjusting-delay task described above. This task presented repeated, hypothetical choices between preventing BC recurrence after varying time delays and avoiding ET side effects immediately. Results: Eighty nine BC survivors participated. Average pill count adherence was near 50%, but self-reported adherence was near 100%. Monetary DD was significantly associated with pill counts; adherence improved with increasing log indifference delays (standardized b 0.328, p = 0.005). Self-report adherence (categorized as discontinued/never started, suboptimal, and perfect) was significantly associated with Cancer DD and income (OR 3.764, p &lt; 0.001 and OR 1.01, p = 0.04, respectively) but not monetary DD (OR 0.978, p = 0.951). No association was found between ET non-adherence and medication type, side effect severity, menopausal status, age, education or minority status. Conclusions: DD may promote ET non-adherence among BC survivors. Behavioral therapies which reduce DD may provide a targeted strategy to improve adherence. More research is needed to develop tools that reliably assess ET adherence and that tailor DD assessments to the cancer survivor population.
Doctors, patients, and the drug industry: Partners, friends, or foes?
Authors: Tiner Richard
Journal: BMJ (2009)

药品企业、学者、医疗专家和患者之间的关系一直以来都不被人看好，这些群体都希望能改善彼此间的关系。皇家外科学院本周提出了42条建议，旨在促进各方和药品企业建立更有成效的关系。这里我们列出有关药品企业和医生与患者之间应该具有什么理想关系的5种观点以及需要采取的相应措施。
PD-L1 expression on tumor cells and tumor infiltrating immune cells in Chinese colorectal cancer patients.
Authors: Jianjun Yang, Guanghui Xu, Jiyang Zheng, Kunli Du, Wei Zhou, Jiangpeng Wei, Haoyu Wang, Anliang Yao, Fuyan Zhao, Yuwei Cong, Xiaochen Zhao, Yuezong Bai
Journal: Journal of Clinical Oncology (2020)

e16111 Background: Nowadays, immune checkpoint inhibitors (ICIs) targeting programmed death-1/ligand-1 (PD-1/PD-L1) have been an alternative in cancer treatments. Previous biomarker analysis found that response to anti-PD1/PD-L1 was associated with PD-L1 expression on tumor cells and/or tumor infiltrating immune cells in some cancer types. Explorations of IMblaze370 study demonstrated better survival outcome in colorectal cancer (CRC) patients with positive PD-L1 expression compared with those with negative PD-L1 expression in the atezolizumab group. Our study investigated PD-L1 expression profile in Chinese CRC population. Methods: PD-L1 expression on tumor cells or tumor infiltrating immune cells in 816 CRC tumors between January 01, 2017 and December 02, 2019 in 3D Medicines database was assessed by immunohistochemistry assay (SP263 or 22C3). We defined percentage of PD-L1 expression on tumor cells as tumor proportion score (TPS) strong positive ≥50%, moderate positive ≥5% and &lt; 50%, weak positive ≥1% and &lt; 5%, and negative &lt; 1%. Similarly, we defined percentage of PD-L1 expression on infiltrating immune cells as immune proportion score (IPS) strong positive ≥10%, moderate positive ≥5% and &lt; 10%, weakly positive ≥1% and &lt; 5%, and negative &lt; 1%. In addition, MSI status was evaluated with targeted next-generation sequencing covering 100 MSI loci. Results: 12 (1.5%) individuals had TPS as strong positive, 63 (7.7%) as moderate positive, 95 (11.6%) as weak positive and 646 (79.2%) as negative. Meanwhile, TPS of patients were 55 (6.7%) for strong positive, 49 (6.0%) for moderate positive, 34 (4.2%) for weak positive and 678 (83.0%) for negative, respectively. 16.9% in Chinese CRC patients here were defined as positive PD-L1 expression (IPS ≥1%), which is lower than the positive proportion of CRC in IMblaze370 study (39.9% for IPS ≥1%, P &lt; 0.0001). The PD-L1 expression on tumor cells and on tumor infiltrating immune cells showed minimal overlap. In detail, only 29 (3.6%) patients exhibited simultaneously TPS positive (≥1%) and IPS positive (≥1%). Furthermore, IPS was not associated with MSI status (P = 0.9153), while TPS showed an association with MSI-H (P &lt; 0.0001). In detail, 45.5% of MSI-H CRC patients were TPS positive. Conclusions: Chinese CRC patients express PD-L1 with 20.8% TPS positive and 17.0% IPS positive, and TPS positive were related to MSI-H. When studying the connection between the efficacy of PD1/PD-L1 inhibitors and PD-L1 expression, TPS and IPS detection would be both considered to engage.
Optimizing the role of general practitioners in organized colorectal cancer screening
Authors: LW Jason Huang, Yuan Fang, Pingping Bao, Yangming Gong, CS Martin Wong
Journal: BMJ (2018)

Organized, population-based colorectal cancer (CRC) screening has been implemented in various cities of China in order to control its rising threat. General practitioners (GPs) play a crucial role as central coordinators among potential screening participants, service providers and program organizers. However, rates of participation and adherence to CRC screening program remain low, whilst its program performance indicators are increasingly receiving more attention. In this review, we summarize the latest literature focusing on strategies to optimize the role of GPs in different stages of organized CRC screening programs, which could substantially enhance screening efficiency and cost-effectiveness of population-based screening programs.


Key words: 
Colorectal neoplasms; Screening; General practitioners; Quality control
National patterns and factors predicting employment disruption in women diagnosed with endometrial cancer.
Authors: Roni Nitecki, Shuangshuang Fu, Benjamin D. Smith, Larissa Meyer, Alexander Melamed, Jose Alejandro Rauh-Hain
Journal: Journal of Clinical Oncology (2020)

e18093 Background: Cancer patients are less likely to return to work after diagnosis. As endometrial cancer is highly curable, it is important to assess whether patients are able to resume work after treatment. We evaluated rates of return to work following endometrial cancer diagnosis and assessed factors associated with a disruption in employment. Methods: A cohort of patients aged 18-63 years who were diagnosed (2010-2015) with endometrial cancer and underwent surgical staging were identified in Truven Marketscan, an insurance claims database of commercially insured patients in the United States. All patients who were working full or part-time when diagnosed were included, and all employment changes during the year following diagnosis were identified. Treatment information, including use of chemotherapy and radiation, and complications of treatment were identified and collected using Common Procedural Terminology codes, and International Statistical Classification of Diseases codes. Univariable analysis and multivariable logistic regression were used to evaluate the impact of treatment and demographic variables on change in employment status. Results: A total of 3547 women with endometrial cancer who held a full-time or part-time job 3 months prior to diagnosis were identified. The median age at diagnosis was 55 years, and the majority of patients (82%) had a Charlson comorbidity index of 0. While most women continued to work following diagnosis, 21% (736) experienced a disruption in employment. The majority (96.7%) held a full-time job prior to going on long-term disability, retirement, or stopping to work. In univariable analysis, chemotherapy recipients were 40% more likely to experience a disruption in employment (Odds ratio (OR) = 1.5, 95% confidence Interval (CI) 1.15-2.11), whereas radiation therapy did not influence employment (OR 1.3, 95% CI 0.99-1.61). In multivariable analysis including age, region of residence, Charlson comorbidity, radiation, chemotherapy, insurance plan and presence of surgical complications, receipt of chemotherapy remained a significant predictor of employment disruption (OR 1.46, p = 0.0257). Conclusions: Twenty-one percent of employed, insured women experienced a change in employment following diagnosis of endometrial cancer, an often-curable disease. Chemotherapy was a significant predictor of employment disruption. This is important to consider in development of interventions to maximize functional recovery following treatment for endometrial cancer.
Some issue about AIDS which should be concerned
Authors: 吴尊友
Journal: BMJ (2006)

随着艾滋病(获得性免疫缺陷综合征,acquired immunodeficiency syndrome, AIDS)的不断蔓延扩散,特别是逐步由高危人群向一般人群扩散[1-3],全科医生在日常诊疗工作中遇到艾滋病患者的机会也越来越多.而多数全科医生对于这种变化,面对艾滋病的到来,可能还没有在思想上和技术上做好准备。
高海拔地区低钾血症致胸导联ST段抬高一例
Authors: 金玉华, 叶平安, 冯宗伦
Journal: BMJ (2005)

患者男,36岁.因双下肢无力6 h于2005年1月6日入院.入院前6 h出现双下肢无力,伴恶心、头晕,无胸痛、心慌.既往高血压病史1年,服用复方降压片(2片/次,3次/d)及北京降压0号(1片/次,1次/d)控制血压;无双下肢无力病史。
预防及识别糖尿病慢性并发症的技巧
Authors: 袁申元, 姜民慧
Journal: BMJ (2009)

袁申元:糖尿病有很多慢性并发症,2型糖尿病是跟肥胖密切关联的,糖尿患者群中70%～80%为肥胖者,因此肥胖是糖尿病的先兆.早在20世纪90年代,WHO提出肥胖是慢性病.肥胖可引起很多慢性病,特别会引起一些严重的慢性病(如糖尿病、冠心病、高血压等),国外统计32～42岁者中,体重额外增加1 kg,死亡的危险性增加1%;50～62岁者中,体重额外增加1 kg,死亡的危险性增加2%。
Monitoring and analysis of syphilis in pregnant women in Baoshan District, Shanghai
Authors: Mei-ju Shi, Xiao-feng Liu, Na Wang
Journal: BMJ (2012)

Objective To explore the epidemiologic feature of maternal syphilis and the status of prevention and control of the disease in Baoshan District. Methods Syphilis monitoring data of pregnant women were analyzed retrospectively in Baoshan district of Shanghai from 2004 to 2009. Results The positive rate of syphilis in pregnant women was 0.31％ ( 195/63 227 ).Among them,residing and migratory pregnant women accounted for 0.17％ (37/22 287) and 0.39％ (158/40 940) respectively (X2 =22.699,P ＜0.01 ). A total of 145 cases received the examination of treponema pallidum particle agglutination (TPPA).And 136 cases were positive.The positive rate of rapid plasma reagin test (RPR) was 51.35％(19/37) in residing early pregnant women and 24.68％ (39/158) in migratory counterparts (X2 =22.192,P =0.000).And 152 cases were followed up to record pregnancy outcomes,including normal delivery of live births ( n =146 ),artificial termination of pregnancy ( n =3 ),stillbirth and spontaneous abortion ( n =3). Forty-three cases became lost. And the rate of loss was 22.78％ (36/158) in migratory pregnant women and 18.92％ (7/37) in residing counterparts. Conclusions It is imperative to improve the prevention and control mechanisms of pregnancy syphilis and the model of consulting services. We should also pay more attention to screening and follow-up work in migratory pregnant women.

Key words: 
Syphilis; Pregnant women; Mass screening
脑卒中的社区康复指导
Authors: 胡永善, 于健君
Journal: BMJ (2012)

脑卒中是我国的常见病、多发病,脑卒中患者存在多种功能障碍,其中以运动和感觉功能障碍最为常见.脑卒中患者进行康复治疗之前、治疗期间和治疗结束时都要进行必要的康复评定,即对脑卒中患者各种功能障碍的性质、部位、范围、程度做出准确的评定.三级康复治疗模式对改善脑卒中患者功能、最大限度的回归社会等方面具有十分重要的意义.社区二级康复治疗,可有效的改善社区脑卒中患者的各项功能,提高患者的生存质量及社会参与能力.应大力发展脑卒中社区康复。
Covid-19: ensuring equality of access to testing for ethnic minorities
Authors: Catherine Dodds, Ibidun Fakoya
Journal: BMJ (2020)

Until successful vaccination programmes are in place governments will be heavily reliant on widespread testing and contact tracing to reduce the reproduction number of SARS-CoV-2. 1 Meanwhile international evidence continues to emerge about ethnic disparities in covid-19 morbidity and mortality, 2 3 echoing the unequal burdens of other global epidemics such as tuberculosis, hepatitis, and HIV.At this crucial juncture, health and policy planners must ensure that access to and uptake of SARS-CoV-2 testing is equitable across all social and economic gradients.We support the recent call for immediate inclusion of social scientists, anthropologists, leaders of marginalised communities, and experts in local social determinants of health in health policy making for this pandemic 4 so that sufficient access, trust, and cultural competence are built in to test, track, and trace programmes for covid-19.Considerable international evidence exists on unequal uptake of medical testing and surveillance across health conditions-including assessment of cancer risk, 5 antenatal screening, 6 and HIV testing. 7 8The disparity is largely attributable to social determinants of health, coupled with mistrust of medical institutions among those in marginalised population groups.Without appropriate action, similar disparities may hamper the success of covid-19 testing interventions.
Association Between Seroclearance of Hepatitis B Surface Antigen and Long-term Clinical Outcomes of Patients With Chronic Hepatitis B Virus Infection: Systematic Review and Meta-analysis
Authors: Ryan T. Anderson, Hannah S.J. Choi, Oliver Lenz, Marion G. Peters, Harry L.A. Janssen, Poonam Mishra, Eric Donaldson, Gabriel Westman, Stephanie Buchholz, Veronica Miller, Bettina E. Hansen
Journal: Clinical Gastroenterology and Hepatology (2020)
The cost of over-intellectualizing the free-energy principle
Authors: Daniel D. Hutto
Journal: Behavioral and Brain Sciences (2020)

Abstract This commentary raises a question about the target article's proposed explanation of what goes on when we think through other minds. It highlights a tension between non-mindreading characterizations of everyday social cognition and the individualist, cognitivist assumptions that target article's explanatory proposal inherits from the predictive processing framework it favours.
Preliminary assessment of low-intensity transcranial magnetic stimulation (TMS) during the treatment for brain glioblastomas.
Authors: Ivan A. Popov, Oleg I. Kit, Alla I. Shikhlyarova, Elena M. Frantsiyants, Eduard E. Rostorguev, Dmitriy P. Atmachidi, Natalya N. Timoshkina, Marina A. Gusareva, Dmitrii S. Potemkin, Vitaliy V. Stasov, Yulia Yu. Arapova, Tatiana P. Protasova, Galina V. Zhukova, Sergey E. Kavitskiy, Sergey N. Ignatov, Islam U. Cherkiev, Emzari S. Nikitin, Natalya S. Kuznetsova
Journal: Journal of Clinical Oncology (2020)

2545 Background: The standard treatment of malignant brain gliomas, including surgical and radiation therapies, does not provide recovery and a long-time favorable prognosis. The development of technologies and international guidelines on the introduction of electric (TTF) and electromagnetic (TMS) fields in combination treatment for glioblastomas aims to improve immediate results, as shown in experiments on human glioblastoma cell culture. The TMS protocol requires further refinement in parameters of frequency, intensity, and exposure with an assessment of the immediate results of combined treatment. Methods: The study included 60 patients diagnosed with MBG receiving osteoplastic craniotomy with radical (within visible unchanged tissues) tumor removal. Starting from the second day after the surgery, patients of group 1 (n = 30) received 10 sessions of magnetotherapy in the double exposure mode. For the first morning exposure, we used an ultra-low-frequency magnetic field (ULFMF) (0.03 to 9.0 Hz) on the hypothalamus projection area to induce a general antistress reaction. After 2.5-3 hours, local (on the surgical site) TMS exposure with the Neuro-MSD system (Russia) was applied in the pulse algorithm, up to 1 GHz and 5 Hz, 15 mT, 3 min. The induction was reduced exponentially (C = 0.8). The control group 2 (n = 30) did not receive ULFMF or TMS. Magnetic resonance imaging (MRI) was used to determine the volume of tumors (Vt, cm 3 ) and perifocal edema (Ve, cm 3 ) calculated according to the Shrek’s formula for an ellipsoid (V = a×b×c×π/6). Results: Before surgery, Vt = 54.7±5.7cm 3 in group 1, in group 2 - Vt = 60.9±8.5cm 3 (no statistical differences). After surgery and the subsequent course of ULFMF and TMS, residual tumor volumes in group 1 were 2.5 times lower than in controls (p &lt; 0.05). The difference between Ve values before and after treatment was on average 80.7 cm 3 in group 1 and 41.8 cm 3 in group 2 (p &lt; 0.05). Conclusions: The inclusion of sequential ULFMF and TMS exposures into postoperative therapy for gliomas, taking into account various vectors of the influence on the projection of centers of homeostasis regulation and the surgical field, as well as the development of programmed modes of biotropic exposure parameters, improves antitumor and anti-edematous effects.