tbuckley/cabot-search huggingface dataset:
Modest Progress on the Path to Electronic Health Record Medication Safety
Authors: Raj M. Ratwani
Journal: JAMA Network Open (2020)

David C. Classen, MD, MS; A. Jay Holmgren, MHI; Zoe Co, BS; Lisa P. Newmark, BA; Diane Seger, RPh; Melissa Danforth, BA; David W. Bates, MD, MSc
Public views towards community health and hospital-based outpatient services and their utilisation in Zhejiang, China: a mixed methods study
Authors: 吴丹, 林大邦, 林国辉, 周旭东, 辛啟成
Journal: BMJ (2018)

目的
中国目前正在全国范围内推广社区卫生服务。本研究旨在探索公众对社区卫生服务的看法，以及他们对于社区卫生服务和医院门诊服务使用情况。


方法
采用定性访谈和横断面调查的混合研究方法。


研究背景和参与者
本项研究于2014年9月至2015年9月期间在中国浙江省进行。全程共开展了6个焦点小组访谈和13个个人深入访谈。调查问卷由1 248名受访者完成（应答率：83%）。


主要结局指标
社区和医院门诊服务的使用。


结果
公众对社区卫生服务职能的认知包括提供轻微病症的诊治、协调、配药、疾病随访和患者教育。然而，许多人仍然对初级保健医生的能力表示不信任，对他们的初步诊断和他们提供的诊疗计划表示怀疑。作为协调员的角色，初级保健医生的诚信也遭到质疑，他们被认为是潜在的托儿 （指试图让患者到一些名誉较差的医院看病进而赚钱的狡诈代理人）。调查结果显示，在过去的一年当中，有800位（64.1%）受访者去过医院门诊就诊，688人（55.1%）去过社区卫生服务机构就诊。与无医疗保险组相比，享受城镇居民医疗保险者[校正后比值比（AOR）=1.95，95%可信区间（CI）1.24~3.07]和享受城镇职工医疗保险者（AOR=2.59, 95%CI 1.59~4.24）更愿意使用医院服务。相对而言，有慢性疾病的受访者使用医院服务（AOR=1.72，95%CI 1.18~2.49）和社区卫生服务（AOR=1.66,95%CI 1.19~2.32）的可能性均更高。收入水平与使用医院门诊的可能性呈正相关（AOR=1.67,95%CI 1.15~2.42），但与使用社区卫生服务的可能性呈负相关（AOR=0.68,95%CI 0.48~0.96）。


结论
公众对医院门诊服务需求远高于对社区门诊服务的需求。政策改革者需要采取进一步的行动来解决公众不信任初级保健医生的问题，进而实现初级保健医生守门员角色的目标。
Measuring PD-L1 mRNA expression using targeted next generation sequencing and correlation with interferon pathway activation genes in lung and colorectal cancers.
Authors: Wanlong Ma, Ivan De Dios, Spiraggelos Antzoulatos, Jeffrey Estella, Maher Albitar
Journal: Journal of Clinical Oncology (2020)

e21534 Background: Expression level of PD-L1 mRNA as determined by next generation sequencing (NGS) is becoming more routinely available in cancer profiling. We explored the relevance of PD-L1 mRNA expression as detected by RNA sequencing in providing information relevant to clinical practice and compared lung cancer with colorectal cancer in activating interferon pathway. Methods: RNA was extracted from 160 non-small cell lung cancers and 53 colorectal cancers (CRC) as well as from 103 samples of various types cancers that were also analyzed for PD-L1 expression by IHC. The RNA sequencing was performed using a targeted panel of 1408 genes. IHC for PD-L1 staining was performed with the FDA-cleared diagnostic assay using the 22C3 antibody. Results: Based on comparing the number of PD-L1 IHC positive tumor cells and CD274 mRNA, significant correlation between the two methodology can be demonstrated as continuous variables (P &lt; 0.0001) as well as when the IHC positivity is grouped as 0 to 1, 2 to 9, 10 to 49, and &gt; = 50 (P &lt; 0.0001). However, cancers with PD-L1 by IHC &gt; 50% had distinctly higher levels of CD274 mRNA, while all other levels of IHC positivity showed significant overlap. Overall lung cancer showed significantly higher levels in STAT1 (P = 0.002), STAT3 (P &lt; 0.0001), STAT4 (P = 0.005), PTPN2 (0.002) as compared with CRC. However, when only CRC cases that show PD-L1 overexpression were considered, there was no significant difference in the expression in any of these genes as compared lung cancer cases that also show PD-L1 overexpression. The only difference is that lung cancer cases with PD-L1 overexpression showed higher levels of IKBKE mRNA as compared with CRC cases with PD-L1 overexpression (P = 0.004). In addition, lung cancer overall showed higher levels of PD-L2 (P = 0.0002), PD-1 (P = 0.0002), CD8A (P &lt; 0.0001), and CD19 (P = 0.0008), but CRC with PD-L1 overexpression showed no difference in the expression of any of these genes when compared to lung cancer cases with PD-L1 overexpression. Conclusions: While CRC shows overall significantly lower RNA levels of PD-L1, PD-L2, PD-1, CD19, CD8A and genes involved in interferon pathway, CRC cases with high expression of PD-L1 mRNA are similar to lung cancer high expressors of PD-L1. Furthermore, PD-L1 quantification using NGS testing can be used to select patient for immunotherapy and might provide valuable information on co-markers that may provide better insight to selecting patients for immunotherapy.
临床思维精粹
Authors: 吴东, 陈嘉林
Journal: BMJ (2010)

一、必须仔细询问病史.因为诊断往往就在其中(listen to the patient,they will tell you the diagnosis) 无论是常见病还是疑难病,就病史、体征和辅助检查相比较而言,对诊断贡献最大的往往是病史。
Clinical utility of a liquid biopsy diagnostic approach in lung cancer using amplicon-based next-generation sequencing in parallel with allele-specific PCR.
Authors: Yukti Choudhury, Wai Min Phyo, Jing Shan Lim, Chaitanya Gupta, Yiliang Ho, Carina Tay, Yuki Sim, Wei Shuen Ng, Michelle Pek, Min-Han Tan, Tan Min Chin, Yew-Oo Tan, Seng Weng Wong, Victor Hsue, William Foo, Wing Kin Sze, Siu Kei AU, Tai Chung Lam
Journal: Journal of Clinical Oncology (2020)

e21516 Background: The utility of a liquid biopsy test for diagnosis and treatment is determined by its accuracy, molecular target coverage and timeliness to a clinically informative result. We describe our clinical experience of providing comprehensive next-generation sequencing (NGS) plasma testing for advanced lung cancer cases, including parallel testing with allele-specific PCR (AS-PCR) for rapid EGFR mutation detection. Methods: Plasma cell-free DNA (cfDNA) from advanced lung cancer patients (n = 374) underwent real-world testing with an amplicon-based NGS assay, in a CAP and ISO15189 accredited central laboratory. The assay covers 51 genes, including 8 guideline recommended biomarkers- EGFR, BRAF, MET, ALK, RET, ROS1, ERBB2 and KRAS. 168 cases (44.9%) were treatment-naïve (baseline) and 206 cases (55.1%) had received one or more lines of treatment. Parallel testing with AS-PCR for 10 specific EGFR mutations was done for 151 cases (90 baseline, 61 non-baseline). Concordance of EGFR mutation detection by the two methods, and the frequency of detection of clinically actionable (driver) mutations by NGS were assessed. Turnaround time (TAT) was calculated from sample receipt. Results: An overall concordance of 97.4% was observed for EGFR mutations between AS-PCR and NGS. When restricted to baseline cases, concordance was 100%. Among baseline cases which were concordant with AS-PCR for EGFR negativity (n = 63), driver mutations were identified in EGFR (n = 7 rarer mutations), KRAS, ERBB2, MET, NRAS, BRAF and ALK (n = 16 total) by NGS, providing an additional 37% diagnostic yield (23/63 cases). Among all baseline cases tested by NGS, a driver gene mutation was found in 64.28% of cases, including EGFR (36.9%) and KRAS mutations (11.9 %). Among non-baseline cases which were EGFR-negative by NGS and by AS-PCR, added diagnostic yield provided by NGS was 33.3% (10 of 30 cases), and included 16.7% rarer EGFR mutations. Overall, detection rate of ALK, RET, ROS1 fusions was 2.4% (n = 5, 3 and 1, respectively). Median TAT for EGFR results by AS-PCR was 1 day (range 1-2 days), while median TAT for NGS results was 10 days (range 4-13 days). Conclusions: We report excellent real-world performance of blood-based liquid biopsy testing for detecting recommended biomarkers in lung cancers, including an approach combining two orthogonal platforms for quick decision making. Clinically meaningful diagnostic yields can be obtained using a timely comprehensive NGS assay, either individually or in parallel with rapid AS-PCR testing.
Development of drug resistance in colon cancer patients following chemotherapy, a contributing factor in the failure of oxaliplatin-based HIPEC to improve survival in the Prodige 7 trial.
Authors: Robert Alan Nagourney, Steven Scott Evans, Paula J Bernard, Adam Nagourney, Peter Tran, Federico Francisco, Paul H. Sugarbaker
Journal: Journal of Clinical Oncology (2020)

4063 Background: Numerous studies suggest benefit for heated intra-peritoneal chemotherapy (HIPEC) in colon cancer but the Prodige 7 trial in 265 colon cancer patients randomized to HIPEC or observation after neo-adjuvant chemotherapy (NACT) didn't confirm benefit with median OS of 41.7 vs. 41.2 mos. (p = 0.99) (Proc. ASCO, 2018). One concern is that prior drug exposure selects for drug resistance blunting HIPEC effect. To test the hypothesis we examined the impact of prior chemotherapy on drug resistance in human tumor organoids isolated from colon cancer patients. Methods: Data query identified 111 colorectal cancers (87 colon &amp; 24 rectal) tested for Oxaliplatin sensitivity by ex vivo analysis of programmed cell death (EVA/PCD), a primary culture platform that examines drug induced cell death (apoptotic &amp; non-apoptotic) by morphology, metabolism &amp; histology. Five-point dose response curves interpolated to provide lethal concentration 50% (LC50) were compared by Z score to distribute Oxaliplatin LC50 values around the mean using standard deviation units as the metric of sensitivity or resistance. Of 87 colon 54(62%) were untreated and 33 (38%) treated with 21/33 (64%) having received FOLFOX. To approximate Prodige 7, treated patients were separated by having received FOLFOX &lt; 2 &gt; months before EVA/PCD analysis and also compared Mitomycin (14 vs 41), Irinotecan (18 vs 47) &amp; 5-FU (19 vs. 52) activity to assess cross-resistance. Results: Compared to chemo-naïve, FOLFOX-treated patients were significantly more resistant to Oxaliplatin (P &lt; 0.01) with the degree of resistance increasing significantly for patients who received treatment &lt; 2 months prior to EVA/PCD compared to those with chemotherapy &gt; 2 months prior to EVA/PCD (P &lt; 0.01). Activity for Mitomycin &amp; Irinotecan was not significantly different for chemo-naïve vs. treated patients, but 5 FU was more resistant (P = 0.048) in previously treated. Conclusions: The failure of Prodige 7 to improve survival with HIPEC following NACT may reflect diminished Oxaliplatin activity in patients whose residual disease has been selected for Oxaliplatin &amp; 5FU resistance. Resistance was not observed for Mitomycin or Irinotecan. This suggests that those using HIPEC may i) examine other classes of drugs or drug combinations for IP administration ii) improve the selection of candidates for HIPEC administration or iii) consider HIPEC administration earlier in the course of therapy when chemotherapy-induced drug resistance may be less evident.
尘肺并急性纤维素性支气管炎一例
Authors: 周一平, 刘慧, 夏利萍
Journal: BMJ (2009)

患者男,38岁,2005年5月12日入院.患者半个月前因受凉后发热,体温波动于38～39℃,无畏寒和皮疹,在深圳市某慢性病防治院查血白细胞计数16.9×109/L,分类中性粒细胞0.88,5月5日的X线胸片诊断为尘肺并右中叶肺炎,疑诊左上肺结核(图1),收入该院治疗.经用阿莫西林-舒巴坦、头孢曲松钠等治疗体温基本恢复正常,但出现咳嗽及少量咯血,且多次咳出白色异常物,5月12日X线胸片见左下肺大片阴影,疑有真菌感染转入我院.患者2年前曾从事山石爆破及采石工作17年,1年前在家乡湖南耒阳诊断为尘肺,现在经商.无烟酒嗜好,既往无咯血史。
High amphiregulin mRNA expression is a strong prognostic biomarker with response to cetuximab in FIRE-1, CIOX, and FIRE-3.
Authors: Arndt Stahler, Sebastian Stintzing, Dominik Paul Modest, Ingrid Ricard, Christine Kapaun, Boryana Ivanova, Ursula Vehling-Kaiser, Ludwig Fischer von Weikersthal, Andreas Schalhorn, Martina Stauch, Alexander Kiani, Jens Neumann, Thomas Kirchner, Volker Heinemann
Journal: Journal of Clinical Oncology (2020)

4026 Background: Amphiregulin ( AREG) and epiregulin ( EREG) were discussed as biomarkers for treatment of metastatic colorectal cancer (mCRC). Data from randomized controlled trials (RCT) are limited. Methods: AREG and EREG mRNA expression by RTqPCR in relation to housekeeping genes were available from 688 patients of three RCT (FIRE-1, n = 192, FUFIRI vs. mIrOx; CIOX, n = 113, cetuximab + CAPIRI/CAPOX; FIRE-3, n = 383, FOLFIRI+cetuximab/bevacizumab) and were normalized to their respective range of each trial with median and 3rd quartile as threshold values. Kaplan-Meier estimated overall survival (OS) and progression-free survival (PFS). Cox regression analysis calculated hazard ratio (HR) and 95% confidence interval (95% CI). Overall response rate (ORR) was compared by chi square test. Results: Across all trials, high AREG mRNA expression appeared as strong prognostic biomarker for OS, PFS and ORR for all threshold values. In RAS wildtype patients, high AREG expression was associated with better OS and PFS for cetuximab but not bevacizumab treatment. (Table) No effects were seen for epiregulin when all trials were analysed together. Conclusions: High AREG mRNA expression appeared as strong prognostic biomarker in mCRC. Positive predictive information might exist for cetuximab treatment. [Table: see text]
Community family physicians in the performances of different management models of chronic disease
Authors: Zhen-yu Li, Chun-tao Yi, Li-zhen Zhu, Wen-dong Tian
Journal: BMJ (2013)

To compare the performances of community family physicians in different patterns of chronic disease management. From June 2011 to April 2012, 3 different models (A, B, C) of chronic disease management were employed for a total of 4972 patients. Statistics analyses were performed. The number of participants, session and average effective working time were different. In terms of standard management of hypertension, diabetic management rate and non on-site management rate, model C was superior to models A and B (P<0.01). And model A had the lowest rate of non on-site management (P<0.05). Though with each own advantage, three models are complementary. But model C reflects the residents' self-management concept of chronic disease.


Key words: 
General practitioners; Disease management
Bronchiectasis combined with pulmonary carcinoma in situ
Authors: Xin Li, Hui Li, Yili Fu
Journal: BMJ (2014)

Bronchiectasis combined with pulmonary carcinoma in situ is very rare condition. This study reported four cases and reviewed some literatures. The data of 66 cases treated from August 2012 to October 2013, whose initial diagnoses as bronchiectases were analysed. Four cases were diagnosed postoperatively as bronchiectasis with pulmonary carcinoma in situ after sugery, accounted for 6% of surgical patients for bronchiectasis. Bronchiectasis has the risk of combined with pulmonary carcinoma in situ, this should be brought to the attention.


Key words: 
Bronchiectasis; Carcinoma in situ
组织多普勒对β受体阻滞剂治疗心力衰竭的疗效评价
Authors: 齐雨青, 朱天刚, 胡大一, 王欣, 权欣, 丁茜, 周倩云
Journal: BMJ (2006)

对21例心力衰竭患者(其中10例服用美托洛尔,11例服用卡维地洛)采用组织多普勒超声测量其左室壁16个节段心脏长轴方向的心肌应变,6个月后重复以上检查.结果示卡维地洛组患者用药后12个节段心肌应变明显增加;美托洛尔组患者用药后10个节段心肌应变明显增加;卡维地洛组平均心肌应变变化量[(-4.6±3.3)%]高于美托洛尔[(-2.4±1.8)%],P<0.05.提示β受体阻滞剂对心肌有保护作用,可改善心肌收缩力;卡维地洛心肌保护作用优于美托洛尔。
RNA sequencing analysis and T-cell receptor repertoire in triple-negative breast cancer (TNBC).
Authors: Ju Won Kim, Yun Suk Yu, Jung Yoon Choi, Soohyeon Lee, Won Jin Chang, Yoon Ji Choi, Seung Pil Jung, Sun-Young Kong, Sung Hoon Sim, Keun Seok Lee, Jin Young Park, Yong Bae Seo, Yeul Hong Kim, Eun Sook Lee, Kyong Hwa Park
Journal: Journal of Clinical Oncology (2020)

1075 Background: Triple negative breast cancer (TNBC) is defined by the lack of two hormone receptors (HR) and human epidermal growth factor receptor 2 (HER2), and well known to have poor prognosis. In this study, we conducted a RNA sequencing including T-cell receptor (TCR) repertoire analysis to develop prognostic biomarker in patients with TNBC. In addition, genes and signaling pathways that correlated with selected biomarker were also investigated. Methods: Total of 78 tumor tissues from TNBC patients were participated for RNA-seq (Illumina Hiseq) analysis. Groups of significant genes were selected by differentially expressed genes (DEGs) analysis, whose expression levels differed more than 1.5 times between patients and normal, or early stage and advanced stage TNBC. Transcript expression levels for prognostic biomarker were analyzed based on R v3.4.3. Using CBS ProbePINGS, a genomic big data analytics platform, we evaluated druggable pathways and protein-protein interaction (PPI). The Interaction Frequency Ratio Score (IFRS) was calculated by investigating highly interactive pathways, and the drugs were matched to patients. TCR repertoire analysis was performed by MiXCR. Results: Ten candidate gene signatures were selected based on RNA sequencing data of each sample. Cross-validation through machine learning showed that the accuracy of the first-ranked signature was 92.3%, the second was 92.0%, and the third was 90.3%. The accuracy of 4 th to 6 th was 88.7%, and the accuracy of 7 th to 10 th was over 88.0%. Cross-validated gene signature, age, and TNM staging showed significant discriminant power under univariate Cox regression analysis (p &lt; 0.05). In the CBS ProbePINGS, human papillomavirus infection, MAPK pathway, and tumorigenesis pathway were correlated with cell signaling. CDK2, FN1, and JUN genes were highly interactive each other. In addition, the drug matching result according to IFRS value suggested imatinib and regorafenib could be possible candidates. TCR repertoire analysis presented that number of clonecount was lower in recurrent or metastatic TNBC than early stage cancer. Conclusions: This study revealed a specific gene signatures that can accurately determine recurrence and metastasis in patients with TNBC based on RNA sequencing analysis. TCR repertoire analysis and CBS ProbePINGS could be valuable method in treatment selection
Chemotherapy remote care monitoring program (CRCMP): Integration of an SMS text patient-reported outcome (PRO) in the electronic health record (EHR) to identify patients needing pharmacist intervention for chemotherapy-induced nausea and vomiting (CINV).
Authors: Shannon Hough, Rachel McDevitt, Victoria Nachar, Shawna Kraft, Anna Brown, Catherine Christen, Barbara Walters, Jeffrey B. Smerage
Journal: Journal of Clinical Oncology (2020)

2001 Background: CINV is a feared side effect of cancer therapy. Despite advances in management, CINV is a common cause for emergency department (ED) evaluation and other unplanned health care utilization. The University of Michigan Rogel Cancer Center initiated the CRCMP to proactively identify patients (pts) experiencing CINV and intervene prior to the need for urgent evaluation. Methods: Pts receiving highly emetogenic chemotherapy are identified by administration of a NK1 antagonist. Once enrolled in the CRCMP, pts receive a daily text message survey for 7 days after treatment. The survey is based on the validated MASCC anti-emesis tool (MAT). Responses are stored within a flowsheet in the EHR. Responses above a set threshold trigger a message to the team pharmacist for intervention. Data presented was reviewed from EHR and claims data. Results: In 8 mo, 652 pts received a NK-1 antagonist (2244 total cycles) and 387 pts enrolled in the CRCMP (59%). Each pt enrolled for an average of 1.8 cycles of chemo (range 1-8). Of patients enrolled, 61.4% were female and 86.2% were Caucasian. Chemotherapy intent was curative for 51.7% and palliative for 48.3% of pts. Pts enrolled most commonly received cisplatin-based (29.7%) followed by carboplatin-based (22.5%), and 5-fluoruracil-based (20.9%) therapy. Text message response rate was 94% (N=18,143 responses of 19,256 total messages sent). During 861 cycles of therapy, 7% of responses noted vomiting and 33% of responses noted nausea. Since implementation of CRCMP, total hospitalization, ED, and urgent care use has decreased (p=0.029) compared to historical data. When utilization for nausea-related diagnoses was considered, the reduction was more notable (Table). Conclusions: Pts engaged in the CRCMP for CINV, allowing for rapid assessment of PROs by a pharmacist. Health care utilization related to nausea was reduced following implementation of CRCMP. While these changes were numerically small, reduction in unnecessary care utilizing PROs can contribute to high value care for cancer patients. [Table: see text]
Potential utility of methylation levels detected from circulating tumor DNA (ctDNA) in predicting molecular residual disease (MRD) in patients with resected non-small cell lung cancer (NSCLC).
Authors: Hong HU, Hang Li, Zelin Ma, Jiaqing Xiang, Yawei Zhang, Analyn Lizaso, Ting Hou, Xiaoqian Guan
Journal: Journal of Clinical Oncology (2020)

e15535 Background: To improve the prognosis of resected lung cancer patients, growing efforts are being invested in finding the most optimal approach to detect MRD and predict relapse. In our study, we aimed to investigate the utility of ctDNA methylation profiling in detecting MRD from patients with resected early-stage NSCLC. Methods: Surgically-resected tumor tissues were obtained from 65 patients diagnosed with resectable stage IA-III NSCLC with various histological subtypes. Matched blood samples were also collected before surgery (baseline) and during regular follow-up after 2-8 weeks of surgery. Comprehensive somatic mutation and methylation level profile from circulating tumor DNA (ctDNA) were performed using unique molecular identifier-based targeted sequencing and targeted bisulfite sequencing, respectively. A tumor-informed MRD prediction model was constructed based on methylation levels obtained from the patient’s resected tumor tissue to calculate the corresponding methylation signal intensity from the matched plasma sample of the patient at baseline or other time points during follow-up, which is reflected as MRD score. Results: Of the 28 patients with baseline ctDNA methylation data, 28.6% (8/28) of the patients had elevated ctDNA methylation levels at first post-operative follow-up (F1) as compared to baseline, indicating the possibility of MRD. Meanwhile, of the 20 patients (71.4%, 20/28) who had reduced ctDNA methylation levels at F1, elevation of ctDNA methylation level was detected from 3 and 1 patients at second (F2) and third (F3) follow-up, respectively. Based on the MRD prediction model, 17.9% (5/28) of the patients had higher MRD scores at F1. Of the 23 patients with lower MRD scores at F1, 5, 1 and 1 patients had an elevation in MRD scores at F2, F3, and F4, respectively, which indicates a possible MRD. Disease relapse was radiologically confirmed after 10-16 months post-surgery in three patients with concomitant elevation of ctDNA methylation level and MRD score during follow-up between 2-9 months prior to radiologic relapse. Conclusions: Our results demonstrate that post-operative ctDNA methylation levels could be used to detect MRD in patients with resected NSCLC. Moreover, ctDNA methylation-based prediction model of MRD could serve as a potential model to predict relapse in early-stage as well as disease progression in advanced-stage NSCLC.