tbuckley/cabot-search huggingface dataset:
Influencing factors and weight analysis for medical graduates to choose general practice in China
Authors: Huiling Xia, Zhigang Pan, Tianhao Wang, Jian Wang, Ming Liu
Journal: BMJ (2020)

Objective
To explore the influencing factors and the weights for medical graduates to choose general practice and work in grassroots posts in China.


Methods
On the basis of pre-investigation, the second interviews were conducted among medical students of grade two to established ahierarchical structure model. A survey was conducted with self-made questionnaire among 407 medical students of grade five from eight medical colleges selected by stratified random cluster sampling from January to June 2017. The influencing factors of choosing general practice choice as the future career were analyzed and the weights were calculated by analytic hierarchy process (AHP).


Results
Total 395 valid questionnaires were received from 161 males and 234 females students. Under the general goal layer of influencing factors for medical graduates to choose general practice, the weights of the four first-level indicators were: career status and prospects for development (weight: 0.299), salary (weight: 0.294), family contribution (weight: 0.207) and professional interest (weight: 0.200). Among the secondary indicators of career status and prospects for development, job satisfaction had the highest weight (comprehensive weight: 0.073), followed by the work environment (comprehensive weight: 0.064), social status (comprehensive weight: 0.061), patterns of doctor-patient relationship in comprehensive care of general practice (comprehensive weight: 0.052), and work intensity had the lowest weight (comprehensive weight: 0.048). Among the five secondary indicators of professional interest, the weight of clinical practice was the highest(comprehensive weight: 0.066), followed by the guidance of theoretical teachers (comprehensive weight: 0.063). In the level 3 indicators in clinical practice, the attitude of general practice teachers to general practice had the higher weight than those teachers in other departments (the comprehensive weights were 0.037 and 0.030, respectively).


Conclusion
Career status and development prospects and salary are the main influencing factors for medical students to choose general practice. Teachers′ guidance in clinical practice and theoretical study is the most critical factor for medical students to be interested in general practice.


Key words: 
Career choice; General Practice; Questionnaires; Grass-roots employment; Medical undergraduate
Implantable cardioverter-defibrillators in dialysis patients
Authors: Mills Mark T, 刘雨
Journal: BMJ (2020)

终末期肾病透析患者极有可能发生心源性猝死（SCD）。一项给透析患者植入心脏复律除颤器的试验，研究了一级预防性植入型心脏复律除颤器（ICD）对左室射血分数（LVEF）≥35%的透析患者所起到的预防死亡的作用。
AST-008: A novel approach to TLR9 agonism with PD-1 blockade for anti-PD-1 refractory Merkel cell carcinoma (MCC) and cutaneous squamous cell carcinoma (CSCC).
Authors: Mohammed M. Milhem, Cesar Augusto Perez, Glenn J. Hanna, Trisha Michel Wise-Draper, Shailender Bhatia, Alice Susannah Bexon, Weston L Daniel, Steven O'Day
Journal: Journal of Clinical Oncology (2020)

TPS3164 Background: AST-008 is a potent spherical nucleic acid configuration of a toll-like receptor (TLR) 9 agonist oligonucleotide being developed for the treatment of MCC and CSCC in patients (pts) progressing on immune checkpoint inhibitor (CPI) monotherapy. Previously presented data suggests AST-008 elicits a Th1-type cytokine response and immune cell activation. This parallel-arm phase II design will permit assessment of efficacy in two advanced skin cancers with high unmet medical need. Methods: The study has an open label, multicenter phase Ib/II dose escalation/expansion design. The phase 1b dose escalation used a 3+3 design with increasing doses of intratumoral (IT) AST-008 plus standard flat dose pembrolizumab. The phase II dose expansion is using the recommended regimen (RP2D) of IT AST-008 plus flat dose pembrolizumab or cemiplimab to treat two cohorts of pts with advanced/metastatic MCC or CSCC, respectively. The key objective of the phase II expansion is to provide an estimate of preliminary efficacy of IT AST-008 with pembrolizumab or cemiplimab in pts whose disease progressed on a single-agent CPI therapy. Endpoints also include safety, pharmacokinetic and pharmacodynamic assessments. Pts must have at least two evaluable lesions by RECIST v1.1. One or more lesions may be injected with AST-008, but one lesion (the “witness” lesion) must remain un-injected throughout the study to differentially assess effects of AST-008 on the injected and witness lesions. The RP2D of AST-008 was derived from the dose escalation phase together with pembrolizumab. That RP2D is being used not only in the MCC cohort where AST-008 is combined with pembrolizumab, but also in the CSCC cohort where AST-008 is combined with cemiplimab. To ensure safety of the AST-008/cemiplimab combination, the first 6 pts in the CSCC cohort will be monitored for dose limiting toxicities through the first 5 weeks of dosing, and then the data review committee will assess safety before approving additional patient enrollment to that cohort. Each expansion cohort will enroll up to 29 pts with a Simon two-stage optimal design. In the first stage, 10 pts will be accrued. If there are 0 responses in these 10 pts, enrollment in that arm will be stopped. Otherwise, 19 additional pts will be accrued for a total of 29. The null hypothesis will be rejected if 4 or more responses are observed in 29 pts. This design yields a type I error rate of 0.05 and power of 80% when the true response rate is 20%. The planned phase II enrollment is 58 pts across about 15 US-based sites. Clinical trial information: NCT03684785 .
Prevalence of diabetes mellitus in outpatients with essential hypertension in China: a cross-sectional study
Authors: 刘军, 赵冬, 刘静, 齐玥, 孙佳艺, 王薇
Journal: BMJ (2014)

目的
了解中国门诊高血压患者合并糖尿病情况及采用空腹血糖(FPG)和口服葡萄糖后2小时血糖(2–hPG))2种检测方法对糖尿病检出率的贡献。


设计
多中心横断面研究。


研究场所
中国22个省市的46家协作医院。


病例
2009年以同一时点开始，46家协作医院依照统一入选标准连续入选门诊治疗的原发高血压患者100例。血糖检测包括FPG和2–hPG(除外有糖尿病史者)。共有4942例20岁以上患者入选。


结果
门诊高血压患者合并糖尿病患病率为24.3%(既往诊断和新诊断)。在1202例糖尿病患者中，417例(34.7%)是本次新检出的。年轻组(年龄<45岁)新检出糖尿病的比例最高(52.6%)。在新检出的417例糖尿病患者中，依靠FPG水平检出的占54.9%，仅依靠2–hPG水平检出的占45.1%。在仅依靠2–hPG检出的糖尿病患者中，空腹血糖水平分布：27.1%FPG<6.1 mmol/L，16.5%FPG<5.6 mmol/L；老年患者中(≥65岁)，32.4% FPG<6.1 mmol/L，24.5%FPG<5.6 mmol/L。


结论
在门诊高血压患者中，糖尿病患病率和新检出率均较高。在空腹血糖检测的基础上增加2–hPG检测，可提高糖尿病检出率，尤其是老年患者。
Osteonecrosis of the jaw (ONJ) in radium 223 (Ra223)-treated metastatic castration-resistant prostate cancer (mCRPC) patients (pts) with exposure to zoledronic acid and/or denosumab.
Authors: Yen Thi Kim Hong Cao, Janson Trieu, Vanessa Rojas, Michael Elias, Michael J. Anderson, Nicholas J. Vogelzang
Journal: Journal of Clinical Oncology (2020)

5575 Background: Bone health agents (BHA) including denosumab, a monoclonal antibody, and Zoledronic acid (ZA), a bisphosphonate, are recommended for men with CRPC and bone metastases to prevent skeletal-related complications. ONJ occurs in about 5% of patients (pts) on BHA. The incidence of ONJ in pts treated with Ra223 and BHA remains unknown, particularly in those who receive sequential treatment of BHAs. Here we describe the rate of ONJ in a real-world setting in mCRPC pts treated with Ra223 in 3 groups: 1) denosumab alone, 2) ZA alone, and 3) sequential ZA /denosumab or vice versa. Methods: A retrospective analysis of a cohort of mCRPC pts with bone metastases who received Ra223. Follow-up was until date of death or last data entry. Chart inclusion criteria included patients who received Ra223 between November 2010 to August 2018 with documentations of data points. Results: A total of 177 pts received Ra223 between 11/2010 and 8/2018. Median age 73 at 1st Ra223 (range 40-93); Median PSA 15.8- at 1st Ra223 (range 0.1-1952); Demographics-AA-10, C-130, Asian-9, unspecified-28; Median Alk Phos 95 at 1st Ra233 (range 25-1515). 93 % (164/177) received BHA. Of the 164 who received BHA, 45% (73/164) received denosumab only, 37% (61/164) received ZA only, and 18% (30/164) received sequential treatment. ONJ developed in 9.7% (16/164) of all patients on BHA. Denosumab alone caused ONJ in 7 of 73 pts (9.6%). ZA alone caused ONJ in 6 of 61 pts (9.8%). ONJ occurred in 3 of 30 pts (10%) in the sequential group. The median number of doses of BHA before development of ONJ was 10 with denosumab, 20 with ZA, and 19.5 (denosumab) and 22 (ZA) in the sequential group. Conclusions: In patients treated with Ra223 and a BHA, the rate of ONJ is 9.7%. The rate of ONJ was similar in groups treated with denosumab alone, ZA alone, and sequential treatment of ZA and denosumab However, ONJ developed more quickly in patients on denosumab. We conclude that the risk of ONJ is increased in patients treated with Ra223 and BHA. ZA or sequential therapy appears to delay time to onset of ONJ compared to denosumab. Clinicians should be mindful of the toxic synergy between Ra223 and BHA. ZA may be the preferred BHA partner with Ra223.
Next generation sequencing reveals the phylogenetic relationship of multi-organ metastatic colon cancer and molecular determinants of metastasis.
Authors: Dandan Hu, Gong Chen, Yaojun Zhang, Minshan Chen
Journal: Journal of Clinical Oncology (2020)

e13502 Background: The clinical manifestation of metastatic colorectal cancer (mCRC) varies from patient to patient, with the underlying genetic alterations and expression profiles deceptive. We aim to investigate the phylogenetic relationships of the multi-organ mCRC and the possible biomarkers of disease progression. Methods: Whole Extron Sequencing (WES) was performed in CRC and their matched multi-organ metastases from three patients with different clinical manifestations. Sciclone calculation between individual lesions illustrated the evolutionary origins of each metastatic sites. Genomic divergence between primary and metastatic sites were identified and their potential role in the metastatic process were annotated. Following the WES results, the significantly correlated genes were validated by immunohistochemistry. Results: The evolutionary tree showed that the distant metastasis could originated from either the primary colon cancer or the other metastatic site. Organotropism exists in both mCRC and protein levels in terms of APOB, and a number of driver mutations potentially decide the disease progression. Moreover, the expressive change of APOB between primary CRC and CRC liver metastasis indicates worse long-term outcomes. Conclusions: Metastatic routes of multi-organ mCRC are highly heterogeneous. We identified previously unreported gene alterations might facilitate metastatic and organotropic progression, providing potential biomarkers for diagnosis and treatment.
Immunohistochemistry analyses of LAG-3 expression across different tumor types and co-expression with PD-1.
Authors: Francine Chen, Thomas Sherwood, Anushka De Costa, Nicholas Yee-Toy, Peter Lung, Ann Easton, Brad Sumrow, Ezio Bonvini, Paul A. Moore
Journal: Journal of Clinical Oncology (2020)

e15086 Background: Concomitant blockade of LAG-3 and PD-1 has been shown to restore T-cell activation and enhance anti-tumor immunity in preclinical models. Clinical trials evaluating anti-LAG-3/anti-PD-1 mAb combinations or bispecific molecules are ongoing. Establishing the tumor expression profile of LAG-3 and its relationship to PD-1 will aid in patient selection and interpretation of clinical responses to combined inhibition. Methods: LAG-3 Ab clone EPR4392(2) (Abcam) and PD-1 Ab clone NAT105 (Ventana) were developed as individual or combined dual IHC assays on the Ventana Discovery Ultra platform. LAG-3 IHC was performed on panels of commercially available tissues: 33 normal human tissues (2 each) and various tumor types including anal (n = 39), cervical cancer (40), cholangiocarcinoma (11), DLBCL (40), gastric cancer (34), HCC (18), SCCHN (39), HER2-positive breast cancer (48), mesothelioma (40), NSCLC (39), ovarian cancer (47), SCLC (48), and TNBC (40). LAG-3 IHC expression was confirmed by in situ hybridization (ACD RNAScope). Positivity was defined as at least one LAG-3+ve or PD-1+ve tumor-infiltrating lymphocyte (TIL) per 40x magnification hot spot field (HSF); high LAG-3 expression was defined as &gt; 15 LAG-3+ve TILs per HSF. Results: LAG-3-specific staining in normal tissues was limited to mononuclear cells in lymphoid organs and GALT, with no staining observed in normal parenchyma. Across various tumor types, the frequency of LAG-3+ve tumor samples and high expression, respectively (%, %), were as follows: cervical (100; 57.5), anal (97.4; 30.8), DLBCL (95; 75), NSCLC (92.3; 25.6), TNBC (90; 22.5), gastric (88.2; 44.1), SCCHN (87.2; 56.4), HER2-positive breast (85.4; 39.6), HCC (83.3; 22.2), cholangiocarcinoma (81.8; 9.1), ovarian (70.2; 21.3), SCLC (50; 14.6) and mesothelioma (25; 10). In addition to TILs, LAG-3 expression was observed on tumor cells in DLBCL and a fraction of anal, breast, cervical, gastric, hepatocellular, SCCHN, NSCLC and ovarian cancers. LAG-3/PD-1 double IHC staining revealed dual positivity across 92.3% of NSCLC samples, with approximately 60% demonstrating TIL co-expression of PD-1 and LAG-3. Conclusions: LAG-3 expression was detected on TILs across a broad range of solid tumors and DLBCL, with varying level of intensity or association with PD-1 expression. Correlative assessments of LAG-3/PD-1 expression with clinical responses to MGD013, an investigational bispecific DART(R) molecule targeting LAG-3/PD-1 (NCT03219268), will be undertaken.
Long-term effect of intensive glucose control on diabetic retinopathy in type 2 diabetes patients
Authors: Gui-feng Xue, Han-jing Fu, Hai-ying Zhou, Shu-ping Zhang
Journal: BMJ (2013)

Objective
To observe the effect of long-term intensive glucose control therapy on diabetic retinopathy in outpatients with type 2 diabetes mellitus.


Methods
Forty-nine patients with type 2 diabetes mellitus were randomly assigned to participate in the trial from 2002 to 2007, receiving either intensive (24 cases) or standard glucose control (25 cases). The patients were examined by the same ophthalmologists to identify any new diabetic retinopathy (DR). After 5 years of intensive glucose control, all of the patients were asked to attend our clinic every 6 months, but no attempts were made to maintain their previously assigned therapies. Hemoglobin A1c (HbA1c) was measured regularly. In November of 2009, a retinal examination was carried out by the same ophthalmologist who worked in the trial. The visual acuity, lens, vitreous body and fundus were examined after pupil dilation to identify diabetic retinopathy (DR). Fundus fluorescein angiography and retinal laser photocoagulation were carried out when necessary.


Results
In the second year after enrollment in the trail, the median HbA1c level of the intensive-therapy group was significantly lower than that of the standard-therapy group [(6.3±0.6)% vs. (7.2±1.2)%, t=2.09, P<0.05], and was maintained in a controlled level throughout the following 4 years. During the post-trial monitoring, no new case of of macula edema or diabetic associated blindness occurred in either intensive or standard-therapy group, the whole occurrence of micro-aneurysms, fundus hemorrhage, as well as those who needed retinal laser photocoagnlation and lowering in visual acuity in intensive-therapy group was lower than that in the standard-therapy group (3 vs. 14 1 vs. 7, 2 vs. 4, 3 vs. 11, respectively; 9 vs. 36, totally, χ2=4.719, P<0.05). During the first post-trial monitoring, there was no difference in median HbA1c level between intensive-therapy group and standard-therapy group [(7.2±1.1)% vs. (7.3±1.3)%, t=0.25, P=0.806], which was sustained in the following years. In the trail, no new case of fundus hemorrhage or diabetic associated blindness occurred in intensive-therapy group during the five-year period of therapy. Number of new episodes of micro-aneurysm, macula edema were less in intensive-therapy group than that in standard-therapy group, number of new episodes of lowering in visual acuity, and those who needed retinal laser photocoagnlation, were significantly less in intensive-therapy group than that in standard-therapy group(15 vs. 25, 4 vs. 23, Z=-4.459, P<0.05) during five-year follow-up.


Conclusions
The benefit of reduced incidence of diabetic retinopathy in intensive glucose can be maintained because of the legacy effect.


Key words: 
Diabetes mellitus, type 2; Intensive glucose control; Diabetic retinopathy
Additional follow-up telephone counselling and initial smoking relapse: a longitudinal, controlled study
Authors: 吴蕾, 何耀, 姜斌, 左芳, 刘庆辉, 张丽, 周长喜
Journal: BMJ (2016)

目的
研究表明戒烟服务能够帮助吸烟者成功戒烟。但是随着时间的增长，很多吸烟者发生了复吸的现象。预防初次复吸对于戒烟者实现长期戒烟的目标具有重要意义。关于电话戒烟干预与防止复吸的研究，已有一些文献报道，但是其结论不尽一致。


设计
从2008年10月至2013年8月，本课题组在北京一个大型综合性医院的戒烟门诊进行了一项纵向对照研究。


参与者
我们将自愿来医院戒烟门诊就诊的吸烟者非随机的分为两组：单纯心理干预组（FC组）和心理干预联合电话干预组（FCF组）。两组吸烟者都没有使用戒烟药物。


结局指标
本研究对FC组和FCF组进行初次复吸时间的比较。使用Cox风险比例模型对吸烟者180天内的初次复吸情况进行多因素分析。


结果
547例自愿接受戒烟服务的男性吸烟者符合本研究的纳入标准。其中457例戒烟者（FC组117例，FCF组340例）至少24小时没有吸烟。大多数复吸发生在戒烟日期后的2个星期内。FC组的研究对象比接受了电话随访干预的研究对象（FCF组）更早复吸，log-rank检验有统计学意义（P=0.003）。Cox回归的结果显示，心理干预联合电话干预、已婚、较低的Fagerstrom评分、正常体质指数和患有医生诊断的烟草相关慢性疾病是防止戒烟者初次复吸的影响因素。


结论
电话随访干预可能是防止复吸的有效措施。由于本研究存在一定的局限性，仍需进一步的研究证实本文的研究结果。
小儿危重症的识别和评估
Authors: 钱素云
Journal: BMJ (2009)

危重症是指危及生命的疾病状态,若不给予及时干预,患儿可能在短时间内死亡.不仅在儿科急诊、门诊、病房,甚至在社区医院都有可能遇到危重患者,即使临床经验丰富的高年资儿科医生对此类患者的处理也如履薄冰.一是由于危重症的基础疾病千差万别、起病多隐匿、进展较凶险;另是因为小儿与成人不同,多不能准确表达不适,且器官功能储备有限,病情进展更难以预料和控制,易引发医患矛盾.此外,对于危重患儿的识别和危重程度评估关系到治疗策略、预后评价、疗效判定等诸多方面。
Correlation between macular structural changes and functional outcomes in idiopathic macular epiretinal membranes
Authors: Yuanyuan Zu
Journal: BMJ (2015)

Objective
To investigate the correlation between macular structural changes and functional outcomes in idiopathic macular epiretinal membranes (IMEM).


Methods
Clinical data of 85 patients with monocular IMEM admitted from April 2013 to April 2014 were retrospectively analyzed. The diseased eyes(85 eyes)were studied as observation group and the normal eyes(85 eyes)served as control group. The results of routine eye examinations, optical coherence tomography (OCT) and multifocal electroretinography (mfERG) were compared between observation and control groups.


Results
The preoperative best corrected visual acuity (BCVA) in observation group was lower than that in control group (0.55±0.17 vs. 0.92±0.14, P 0.05). BCVA in observation group was negatively correlated with CRT(r=-2.16, P<0.05).


Conclusions
The central retinal thickness is negatively correlated with the best corrected visual acuity, but not correlated with center mfERG in patients with IMEM.


Key words: 
Macular degeneration; Tomography, optical coherence; Electroretinography
糖尿病老年患者血糖的渐进性控制
Authors: 王滟, 迟家敏, 潘琦, 蒋蕾, 李慧, 郭惠琴
Journal: BMJ (2005)

对需要胰岛素治疗的患者,主管医生习惯根据患者治疗前的血糖数值,按照通常的公式计算胰岛素剂量,使血糖在短时间内达到正常水平.但是,对于糖尿病老年患者,由于可能存在多种健康问题,应特别强调个体化临床思维,在血糖控制问题上施行渐进达标的方式进行治疗,现结合4例具体病例进行讨论。
外阴上皮内非瘤样病变的诊治现状
Authors: 崔满华, 许天敏, 祝贺
Journal: BMJ (2011)

外阴上皮内非瘤样病变又称外阴皮肤和黏膜上皮内非瘤样病变(nonneoplastic epithelial disorders of skin and mucosa),是指女性外阴皮肤和黏膜组织发生色素改变和变性的一组慢性疾病,以局部瘙痒或疼痛及肉眼可见的病损为共同特点,既可以单独出现,也可以是全身疾病的一部分。
Efficacy and tolerance of carboplatin-cetuximab in patients with metastatic or recurrent head and neck squamous cell carcinoma unfit for extreme regimen.
Authors: Charlotte Le Roy, Dewi Vernerey, Cecile Evin, Celine Crespel, Thomas Samaille, Christophe Le Tourneau, Florence Huguet
Journal: Journal of Clinical Oncology (2020)

6539 Background: Head and neck squamous cell carcinoma (HNSCC) is the fourth cause of death by cancer in France. For metastatic patients, the standard first line treatment is the EXTREME regimen. However, a lot of these patients have a poor performance status (PS) and/or several comorbidities making them unfit for this regimen. We have treated them with carboplatin and cetuximab (simplified EXTREME regimen) since 2007. The aim of this study is to assess the efficacy and tolerance of this regimen in this frail population. Methods: We retrospectively reviewed the medical charts of all patients treated with simplified EXTREME regimen for recurrent or metastatic HNSCC in three French academic hospitals between 2007 and 2017. The primary endpoint was overall survival (OS) and secondary endpoints were progression free survival (PFS), overall response rate (ORR), identification of prognostic factors, and toxicity. Results: 103 patients were included with a median age of 63 y.o., 60% had a PS 0-1 and 40% a PS 2-3. With a median follow-up of 30.2 months, median OS was 7.2 months and median PFS 3.7 months. ORR was 39% and 24% of patients had disease stabilization. On univariate analysis, a PS of 2 or more was significantly associated with a worse OS (median OS 10.1 months if PS 0-1 versus 4.6 months if PS 2-3; HR = 1.68; 95%CI = 1.11-2.57; p = 0.01). Acute grade 3-4 hematologic and non-hematologic toxicity rates were 25.2% and 27.2%, respectively, with 11.8% of thrombopenia, 9.7% of neutropenia, 10% of skin toxicity, and 12.6% of asthenia. Patients with grade 1 or more skin toxicity had a higher ORR (HR = 3.44; 95%CI = 1.16-10.23; p = 0.03) and a prolonged OS (HR = 0.37; 95%CI = 0.23-0.58; p &lt; 0.0001) and PFS (HR0.29; 95%CI = 0.19-0.47; p &lt; 0.0001). During treatment, 29% of patients had a pain decrease, 13.5% a gain of weight, and 17.2% an improvement in PS. Conclusions: This is the largest cohort of patients treated with simplified EXTREME for HNSCC. Simplified EXTREME was well tolerated in this frail population with a high ORR. Patients with a good PS had prolonged survival. Interestingly, skin toxicity of any grade was significantly correlated with treatment efficacy.
Clinical and electroencephalographic manifestations of Hashimoto′s encephalopathy
Authors: Jihong He, Fengyun Tang
Journal: BMJ (2015)

Clinically rare with an acute or subacute onset, Hashimoto′s encephalopathy (HE) is characterized as autoimmune encephalopathy with elevated anti-thyroid autoantibodies. If timely diagnosed and treated, its prognosis is often fair. Four HE cases admitted from January 2012 to June 2014 were analyzed with a literature review. HE 4 cases had a significantly higher level of thyroperoxidase (TPO) while the lowest increase over four folds. There were cognitive decline, memory loss and even coma. And 50% had abnormal electroencephalogram (EEG) consistent with radiographic lesions. In short, EEG may aid an early diagnosis of HE.


Key words: 
Hashimoto encephalopathy(HE); Electroencephalogram