tbuckley/cabot-search huggingface dataset:
临床操作技能评估在全科医师能力评估中应用简介
Authors: 陈倩, 祝墡珠
Journal: BMJ (2012)

随着医学的发展,临床医师的能力培养与评估逐步受到重视.Miller[1]在1990年提出能力金字塔的概念,将临床医学教学分为知识的记忆( know)、整合(know how)、转化( show how)和应用(do)4个阶段,形象地说明医学生和临床医师在学习过程中由知识积累到临床实践能力形成、发展、运用的过程.临床操作技能评估(direct observation ofprocedural skills,DOPS)与小型临床演练评估(mini-CEX)、客观结构化临床测试( OSCE)均为住院医师临床能力评估的重要工具[2-3],主要用于评估知识转化、应用的能力。
Abstract 18968: A Crispr Interference Platform in Human Induced Pluripotent Stem Cell Derived Cardiomyocytes for the Characterization of Gene Loss-of-function in Cellular Electrophysiology
Authors: Ling Xiao, Sebastian Clauss, Ellen Bailey, Patrick Ellinor, David Milan
Journal: Circulation (2016)

Introduction: The recent development of CRISPR interference (CRISPRi) shows highly efficient and specific gene silencing in different cell types including human induced pluripotent stem cells (iPSC...
The prognostic value of APACHE II and SOFA scores in the elderly critical patients
Authors: 乔青, 周伟炜, 宋以信
Journal: BMJ (2007)

目的 探讨急性生理和慢性健康评价Ⅱ(APACHE Ⅱ)评分和序贯器官衰竭估计(SOFA)评分对老年危重患者的预后评价作用.方法 选取2005年1月至12月收治年龄≥65岁、至少有2个系统功能障碍的患者106例,计算入住ICU当日的APACHE Ⅱ评分和SOFA评分,并且每隔48 h计算SOFA评分直到离开ICU.按转归分为存活组(72例)和死亡组(34例),比较两组患者APACHE Ⅱ评分和SOFA评分;观察患者入院2周内SOFA评分的动态变化;判断APACHE Ⅱ和SOFA评分系统的预测分辨力及校准力.结果 存活组的APACHE Ⅱ分值和SOFA分值均低于死亡组,差异有统计学意义(P＜0.01).存活组在进入ICU 2周内SOFA分值逐渐下降,而死亡组则逐渐增高,两组的变化有统计学意义(P＜0.01).APACHE Ⅱ和SOFA初始评分经相关分析,r值为0.551,P值为0.00.APACHE Ⅱ评分预测死亡率的工作特征曲线下面积为0.77,SOFA初始、SOFA48 h、SOFA96 h、△SOFA、SOFA最大预测死亡率的工作特征曲线下面积分别为0.73、0.90、0.95、0.98、0.99.APACHE Ⅱ评分的Lemeshow-Hosmer值为7.22,差异无统计学意义(P＞0.05).结论 APACHE Ⅱ评分及连续应用SOFA评分能够准确判断老年内科危重患者疾病的严重程度和预后,其中SOFA最大评分和△SOFA评分的预测能力最佳.联合应用APACHE Ⅱ评分和SOFA评分对老年危重患者进行病情评价,可提高预测的准确性。
Application of formative assessment in standardized general practice residency training
Authors: Yanling Song, Shenhong Gu, Yunyun Lin, Huade Mai
Journal: BMJ (2018)

Forty three medical graduates from Hainan Medical University participating in the standardized general practice residency training in 2015 and 2016 were randomly divided into study group (n=22) and control group (n=21). The study group received a mid-term assessment and formative assessment, and the control group received the final assessment only. At the end of the six months of training, the scores of the mid-term assessment in study group were significantly higher than those in the control group [(82.9±8.4) vs. (75.5±10.2), t=12.706, P<0.01]. A questionnaire survey was conducted among the participants in study group, 86.4% of them recognized and supported the formative assessments. Formative assessment can improve the teaching quality of general practice residency training. The trainees have a positive attitude towards this assessment mode.


Key words: 
General practice; Resident; Standardized training; Formative assessment
Next generation sequencing analysis of key genes in breast cancer patients from Kazakh population.
Authors: Aliya Abdrakhmanova, Nazgul Omarbayeva, Dilyara Kaidarova, Gulnur Zhunussova, Saltanat Abdikerim, Saule Yessenkulova, Aizhan Jakipbayeva, Zhanna Chingissova, Leila Djansugurova
Journal: Journal of Clinical Oncology (2020)

e13548 Background: Breast cancer (BC) shows a high incidence both in Kazakhstan and worldwide. Approximately 20-30% of cases of hereditary breast cancer are caused by presence of BRCA1/2 genes defects. Also, there are additional genes, which can increase the risk of BC and they are still under study. In our study we identify new, detectable and objective markers of key cancer genes by next-generation sequencing (NGS) of young BC patients in Kazakh population. Methods: The study enrolled 235 unrelated patients from Kazakh population(the average age 34.25 ± 4.56) with BC. Genomic DNA was obtained from peripheral blood and sequencing was performed using TruSight Cancer Kit on the MiSeq platform. Studio Variant was used to annotate and interpret genetic variants. 26(11.1%) patients had a maternal family history of BC, 21 (80.8%) of them had first- degree relatives diagnosed with BC at different age. Results: Bioinformatics analysis of NGS data identified 23,915 variants in 83 genes. 64 pathogenic variants in the heterozygous state were found in 62 (26.4%) patients, 8 (12.5%) variants were not previously described in databases (LOVD, ClinVar, 1000 Genomes, ESP6500 and ExAC). The most frequent pathogenic mutations were in the genes BRCA1 (24 variants (37.5%) and BRCA2 (18 (28.1%)). Additional pathogenic variants were identified in the non-BRCA genes (APC, ATM, BLM, CHEK2, PALB2, TP53, ERCC2, FANCA, FANCM, NBN, PMS1, PMS2, SDHB and XPA). A hereditary history was recorded in 29.1% and 27.8% of representatives of the group with pathogenic mutations in the BRCA1 and BRCA2, respectively, higher compared to the group of patients without pathogenic mutations and to the group of patients with non-BRCA genes. Conclusions: The frequent and novel germline mutations in BRCA1/2 and non-BRCA genes were identified by NGS. Diagnostic and prevention tools for key genes are considered to be developed and included in the National guidelines of Republic of Kazakhstan after final statistic data processing.
Neuroleptic rotation for refractory agitation in cancer patients with delirium in the acute palliative care unit: A double-blind randomized clinical trial.
Authors: David Hui, Allison De La Rosa, Annie Wilson, Thuc Nguyen, Jimin Wu, Marvin Delgado Guay, Ahsan Azhar, Joseph Anthony Arthur, Daniel E. Epner, Ali Haider, Maxine Grace Jaucian De La Cruz, Yvonne Heung, Kimberson Cochien Tanco, Shalini Dalal, Terri Armstrong, William Breitbart, Eduardo Bruera
Journal: Journal of Clinical Oncology (2020)

12006 Background: Terminal agitation commonly occurs in the last days of life and is highly distressing. The role of neuroleptics is controversial and few studies have examined agitation as a primary outcome. We assessed the effect of 3 neuroleptic strategies on refractory agitation in cancer patients with terminal delirium. Methods: In this single-center, double-blind, double-dummy parallel group randomized trial, patients admitted to a palliative and supportive care unit with refractory agitation despite low dose haloperidol were randomized in a 1:1:1 ratio to (1) haloperidol dose escalation, (2) neuroleptic rotation to chlorpromazine, or (3) combined haloperidol and chlorpromazine. Intravenous medications at equivalent doses were scheduled every 4 h and every 1 h as needed until discharge. The primary outcome was change in Richmond Agitation Sedation Scale (RASS) from time 0 to 24 hours. With 15 patients per group and 13 measurements over time, we had 90% power to detect an effect size of 0.2 with alpha=2.5%. One way ANOVA was used to examine within group differences. We also compared among groups with the Wilcoxon rank sum test. Results: 68 patients were enrolled and 45 received the blinded study interventions. The median survival was 73 h (95% CI 49, 106 h). RASS decreased significantly within 30 minutes and remained low at 24 hours in the dose escalation group (mean RASS change between 0 and 24 h [95% CI]: -3.6 [-5, -2.2]) v. rotation group (-3.3 [-4.4, -2.2]) v. combination group (-3 [-4.6, -1.4]), with no difference among groups (P=0.71). A majority of patients were perceived to be more comfortable after treatment by blinded caregivers (escalation v. rotation v. combination: 62% v. 71% v. 60%; P=0.83) and bedside nurses (64% v. 75% v. 64%; P=0.82); however, the rotation group had significantly fewer breakthrough restlessness (escalation v. rotation v. combination: 73% v. 19% v. 50%; P=0.009), required fewer upward dose titration (escalation v. rotation v. combination: 27% v. 6% v. 50%; P=0.03) and required less rescue neuroleptics in the first 24 hours (haloperidol equivalent: 4 mg vs. 2 mg vs. 6 mg, P=0.09, trend only). Hypotension was more frequently observed with chlorpromazine. Overall survival did not differ (&gt;0.99). Conclusions: Preliminary data from this study supported that all 3 strategies of neuroleptics reduced agitation and improved comfort in patients with terminal delirium; however, neuroleptic rotation provided better agitation control and confirmatory studies are needed. Clinical trial information: NCT03021486 .
Toxicities with combination BRAF and MEK inhibition in resected stage III melanoma.
Authors: Govind Warrier, Morgan Homan, Christopher D. Lao, Sarah Elizabeth Yentz, Shawna Kraft, Leslie Anne Fecher
Journal: Journal of Clinical Oncology (2020)

e22086 Background: Patients with stage III melanoma are at high risk for recurrence after resection of the primary lesion. The Combi-AD study showed adjuvant therapy with BRAF inhibitor, dabrafenib (D), and MEK inhibitor, trametinib (T), in patients with resected stage III BRAF mutant melanoma offers recurrence free survival benefit at 3 and 4 years compared to placebo. In this study, adverse events led to dose interruption in 66% of patients, dose reduction in 38% of patients, and permanent discontinuation in 26% of patients. This is a retrospective case series of patients with resected stage III melanoma treated with adjuvant BRAF and MEK inhibition reporting toxicities in a real-world population. Methods: Medical records of all patients with resected Stage III melanoma treated with adjuvant D+T by multiple, independent oncologists at our institution between November 2017 and December 2019 were reviewed. Planned treatment was dabrafenib 150 mg bid and trametinib 2 mg daily for 1 year. Primary outcome of interest was development of toxicities. Secondary outcomes included number of treatment interruptions, dose reductions, and total time on combination therapy. Results: Twenty patients were treated with adjuvant D+T during the study period. Eighteen patients (90%) required at least 1 treatment interruption due to adverse events. Eleven patients (55%) required a dose reduction and 14 (70%) permanently discontinued therapy due to an adverse event. The 9 patients who did not require dose reduction had been initiated on a lower dose of dabrafenib (75 mg BID) due to physician experience with toxicities in prior patients. The most common treatment-limiting adverse events were recurrent pyrexia (85%) and liver laboratory abnormalities (50%). Permanent discontinuation was secondary to recurrent pyrexia in 9 patients (45%) and liver laboratory abnormalities in 5 patients (25%). For the 16 patients who completed or discontinued therapy, the median total time on therapy was 76 days, 20.8% of the intended duration. The majority of these patients never reached the FDA labeled combination dose. Conclusions: We report our findings of the side effects of adjuvant D+T to demonstrate the frequency and severity of treatment limiting toxicities in a real-world population, which exceeds what has been reported in clinical trials. Adjuvant D+T is an approved treatment for resected stage III melanoma but requires diligent toxicity assessment and management.
Current status and training requirements for retraining program of general practitioner
Authors: Zhi-hong Zheng, Li-ge Liu, Su-xian Yuan
Journal: BMJ (2013)

The current status and training requirements for general practitioner (GP) were surveyed with questionnaires in 84 trainees from the first Beijing GP retraining program. Results showed that three most demanded skills of health service in community were electrocardiogram (98.8%), clinical lab results reading (96.4%), dressing change (90.5%). The services not provided but should be provided in community were aerosol rebreathing method (23.8%), resection of small superficial lumps (22.6%) and reading X-ray films (20.2%). The reasons for services not provided were insufficient resources (41.7%), lack of skilled personnel (35.7%) and staffing shortage (20.2%). The most required training skills were reading X-ray films (64.3%), electrocardiogram (54.8%) and laboratory results reading (51.2%). There were some skills inadequately trained including cricothyroid membrane puncture, suprapubic bladder puncture and resection of superficial small lumps. The results indicate that the required skills in community health service and individual demands of general practitioners should be the priority of the future training programs.


Key words: 
Inservice training; Questionnaires; General practitioners
A case of tumor-like calcinosis in the posterior of calcaneus
Authors: Yanjing Zhang, Li Zhang, Xiaoli Ling
Journal: BMJ (2019)

肿瘤样钙盐沉积症是少见的骨外钙化性疾病，主要发生于关节周围软组织内，常见部位包括臀部、肩部、腰部及肘部，很少累及手足关节。本文报道1例跟骨后肿瘤样钙盐沉积症的临床发病特点及其影像学表现，提高对本病的认识。
Effects of chronic periodontitis on heart attack and stability of coronary artery disease
Authors: 张善春, 刘长兰, 郑刚, 杨顺来, 王劲
Journal: BMJ (2004)

目的 探讨慢性牙周炎对冠心病发病和病情稳定性的影响.方法对266例冠心病患者(急性心肌梗死72例,不稳定心绞痛91例,稳定性心绞痛103例)和266例正常对照者进行口腔检查,比较缺失牙齿数目及牙周指数.结果冠心病组牙周指数高于对照组(P<0.01),调整性别、年龄、体重指数、吸烟史、高血压病及糖尿病史、血脂指标、C反应蛋白、白细胞计数及纤维蛋白原水平后, 牙周指数仍与冠心病患病率显著相关,比数比为1.762(P<0.05).急性心肌梗死组及不稳定心绞痛组的牙周指数,与对照组和稳定性心绞痛组比较差异均有显著性(P<0.05),稳定性心绞痛组与对照组相比差异有显著性(P<0.05).缺失牙齿数目在各组间差异无显著性.结论慢性牙周炎影响冠心病发病和病情稳定性,是冠心病的独立危险因素。
Real-world treatment patterns among patients with diffuse large B-cell lymphoma (DLBCL) treated with CD19-directed chimeric antigen receptor T-cell therapy (CAR T).
Authors: Jessica J. Jalbert, Jon E. Arnason, Wenzhen Ge, Chieh-I Chen, Srikanth R. Ambati, Ning Wu, Aafia Chaudhry
Journal: Journal of Clinical Oncology (2020)

e19351 Background: CAR T, approved in the US as of October 2017, impacted the treatment landscape for patients with relapsed or refractory (R/R) DLBCL after ≥2 lines of therapy, but there is little known about real-world (RW) treatment patterns in patients who fail or do not respond to CAR T. No treatments of proven benefits are available after CAR T treatment failure. The objective of this study was to describe RW treatment patterns after CAR T. Methods: From MarketScan Commercial/Medicare claims databases (2017‒2018) we identified adult DLBCL patients who received approved CD19-directed CAR T (treatment date = index date). Eligible patients had ≥6 months continuous health plan enrollment prior to index date (i.e. baseline period) and were followed until plan disenrollment or December 31, 2018. Patients with a diagnosis of acute lymphoblastic leukemia over the baseline period were excluded. We identified the first and second treatments after CAR T with systemic chemotherapy, targeted therapy, immunotherapy, hematopoietic stem cell transplant (SCT), radiation therapy (RT), or a second round of CAR T therapy. Kaplan–Meier estimators were used to estimate risk of subsequent treatment and time to next treatment. Results: We identified 56 patients with DLBCL treated with CAR T (mean age [SD]: 57.3 years [9.9]; 23.2% female; 80.4% commercially insured). All patients received CAR T in the inpatient setting, median (Q1‒Q3) length of stay was 15 days (12‒19). Out of 56 patients, 19 initiated a treatment following CAR T; risk of subsequent treatment at 6 months post index was 45.6% (95% CI: 25.4‒60.4%) and median days from CAR T to next treatment was 233 days (95% CI: 139‒NA). Out of 19 patients, 3 initiated a second treatment following CAR T, within 8‒69 days of the first treatment. Over a median (Q1‒Q3) follow-up of 139.5 days (90.5‒194) following CAR T, of the 19 patients treated after CAR T, 57.9% were treated with immunotherapy, 36.8% with RT, 26.3% with targeted therapy, 21.1% with SCT, 15.8% with chemotherapy, and 0% with a second round of CAR T. Conclusions: There are few multicenter studies reporting RW treatment patterns in patients who received CAR T. In this study, risk of subsequent treatment at 6 months following CAR T in a RW setting was almost 50%. Although limited by duration of follow-up, our results suggest that additional, effective salvage treatment strategies are needed for patients who do not respond to CAR T or do not achieve a durable response to CAR T. Updated results using 2019 data will be presented.
The FLEX real-world data platform explores new gene expression profiles and investigator-initiated protocols in early stage breast cancer.
Authors: Nina D'Abreo, Jennifer A. Crozier, Adam Brufsky, Ian Grady, Sami Diab, Blanche H. Mavromatis, Carrie L. Dul, Rakhshanda Layeequr Rahman, Laura A. Lee, Vijayakrishna K. Gadi, Sarah Untch, Erin Yoder, Heather M. Kling, Amy Truitt, William Audeh
Journal: Journal of Clinical Oncology (2020)

TPS7088 Background: Genomic expression profiles have enabled the classification of breast cancers into molecular sub-types and provide prognostic information about the metastatic potential of the tumor, both of which have implications for the personalized treatment of breast cancer beyond clinical and pathological features. However, to precisely stratify tumors into actionable subgroups, full genome expression data should be combined with comprehensive clinical information. The FLEX Registry aims to aggregate a large, real-world dataset, which will enable discovery of novel genomic profiles, particularly for patient subsets that are underrepresented in traditional clinical trials and will contribute to improved precision in the management of breast cancer. Methods: The FLEX Registry (NCT03053193) is a multi-center, prospective, observational trial for patients with Stage I, II, and III breast cancer. Patients with stage I-III breast cancer who receive the 70-gene signature risk of recurrence test, with or without the 80-gene signature molecular sub-typing test, on a primary tumor are eligible for enrollment. The primary objective of FLEX is to create a large scale, population-based registry that links complete clinical data with full genome expression data to elucidate new prognostic and/or predictive gene associations in a real-world setting. The FLEX Registry employs a shared study infrastructure to develop and investigate hypotheses for targeted subset analyses and/or clinical trials based on full genome expression data. The adaptable protocol is designed to be amended with the inclusion of targeted sub-studies. Patients enrolled in the initial study are eligible for inclusion in sub-studies for which they meet all eligibility criteria and additional consent is not required. Data will be collected on patients from diagnosis through 10 years of follow-up and any necessary additional clinical data will be collected as specified in the appendix protocols. Target enrollment is a minimum of 10,000 patients; &gt;4,000 patients have enrolled since April 2017 at more than 80 sites, including seven National Cancer Institute-designated comprehensive cancer centers. The FLEX collaborative platform enables participating investigators the opportunity to author their own sub-study protocols, as approved by the FLEX Steering Committee. Fifteen sub-studies have been approved for investigation within the FLEX Registry. Clinical trial information: NCT03053193 .
Chemotherapy-induced neutropenia among breast cancer patients presenting to a tertiary hospital in Nigeria.
Authors: Omolola Salako, Kehinde Sharafadeen Okunade, Adeoluwa Akeem Adeniji, Gabriel Fagbenro, Oluwasegun Afolaranmi
Journal: Journal of Clinical Oncology (2020)

e12523 Background: Neutropenia and febrile neutropenia are major dose-limiting adverse effects of systemic cancer chemotherapy. It has been associated with significant morbidity and mortality, and high costs of management, and treatment breaks in cancer patients especially in resource-limited environments leading to poorer outcomes. Chemotherapy-induced neutropenia is an established complication of breast cancer treatment, however, there is paucity of information on the exact magnitude of the condition. This study assessed the prevalence of neutropenia and febrile neutropenia, while identifying their associated factors. Methods: A cross-sectional study was conducted among 113 female chemotherapy-naïve breast cancer patients over a two-year period. Sociodemographic, clinical and haematological data was obtained via semi-structured interviews and from medical case files. Blood samples for complete blood count parameters were collected after each course of chemotherapy. The National Cancer Institute Common Terminology CTCAE version 4.03 was used to assess febrile neutropenia, neutropenia and its severity. Results: The prevalence of neutropenia and febrile neutropenia among the patients was 31.9% and 5.3% respectively. Throughout all courses of chemotherapy, there were neutropenic episodes 11.4% (57/502) with mild neutropenia 6.6%, moderate 3.4% and severe 1.4%. Prevalence of neutropenia decreased with increasing chemotherapy courses, with prevalence after first course being 14.2% and last course 4.9%. Associated risk factors for developing neutropenia include increasing age ( p = 0.014), ECOG performance score &gt; 1 at presentation (p = 0.033) and presence of bone metastasis (p = 0.002). Conclusions: One in three breast cancer patients developed neutropenia while on chemotherapy. The use of prophylactic G-CSF after each course of chemotherapy should be a routine practice, especially among elderly patients, unstable patients, and those with bone metastasis.
Activity of front-line window therapy with temozolomide plus irinotecan in patients with primary multifocal Ewing sarcoma: ISG/AIEOP EW-2 protocol.
Authors: Asaftei Dorin Sebastian, Nadia Puma, Anna Paioli, Marco Petraz, Carlo Morosi, Marta Giorgia Podda, Angela Tamburini, Luca Coccoli, Giovanni Grignani, Carla Manzitti, Rossella Bertulli, Francesco De Leonardis, Marco Rabusin, Piero Picci, Arcangelo Prete, Alessandra Longhi, Franca Fagioli, Roberto Luksch
Journal: Journal of Clinical Oncology (2020)

10516 Background: The prognosis of patients with primary multifocal metastatic Ewing sarcoma (PMES) remains dismal. So far, combination with temozolomide and irinotecan (TEMIRI) was tested in patients with refractory or relapsed disease. This study evaluates the activity and the tolerability of TEMIRI as front-line treatment in PMES. Methods: In the study-period 2012-2018, a front-line window therapy with 2 courses TEMIRI (temozolomide 100 mg/sqm/day + irinotecan 50 mg/sqm/day for 5 days every three weeks) was introduced as amendment to the ISG/AIEOP EW-2 protocol ( EUDRACT#2009-011197-15, Vers. 1.02 ) for patients with PMES. Main objective was to test the activity of TEMIRI evaluated by RECIST 1.1 criteria, with centralized revision of the radiological response. Secondary objectives included assessment of the toxicity profile and clinical benefit of the combination. A two-step study design by Simon was planned. Results: Thirty-four patients were enrolled. Median age at diagnosis was 19 years (range 3-55); males/females ratio was 2.4. Primary axial tumour was present in 24 (70%). After TEMIRI, RECIST response was as follows: partial response -20 (59%), stable disease -11 (32%), progression disease -3 (9%). After TEMIRI, amelioration in ECOG/Lansky score was achieved in 25/34 (73,5%), and reduction or disappearance of pain was observed in 31/34 patients (91%). TEMIRI toxicity was manageable: incidence of grade 3-4 nonhaematological and haematological toxicity was 3% and 3%, respectively (67/68 evaluable courses). At the time of the present analysis, 11 patients are alive; 7 of them are in complete remission and completed their treatment program (5-drug standard chemotherapy). With a median follow-up of 31 months (range 23-75), the 3-year survival estimate is 36,5%±0.09. Conclusions: Upfront TEMIRI x 2 courses showed an encouraging activity, with response rate 59% and deserves further evaluation combined with conventional treatments also in non-metastatic patients. In PMES new treatment strategies are urgently needed. Clinical trial information: NCT02727387.