tbuckley/cabot-search huggingface dataset:
Monitoring of nosocomial infection in intensive care unit
Authors: Xiu-li Zou, Ying-ren Wang, Lian-rong Zhang, Yan-hua Li, Hong Jin
Journal: BMJ (2010)

The data on nosocomial infection of 4060 patients who were stayed in intensive care unit (ICU) more than 48 h from January 1997 to August 2008 were reviewed.From Jan 2004 the target monitoring of hospital-acquired infection was implemented in ICU.The nosocomial infection rates before and after target monitoring were 35.25% (871/2471) and 30.77% (489/1589) respectively (P ＜ 0.01);however there was no significant difference in case infection rate before and after target monitor were practiced (47.67% vs.45.25%,χ~2 = 2.2836,P ＞0.05).The incidence of Acinetobacter infection was increased after target monitoring.Targeted monitoring can decrease the nosocomial infection rate in ICU,and also reduce the cost of medical care.

Key words: 
Intensive care units;  Cross infection
A phase I/II study of REGN5678 (Anti-PSMAxCD28, a costimulatory bispecific antibody) with cemiplimab (anti-PD-1) in patients with metastatic castration-resistant prostate cancer.
Authors: Charles G. Drake, Jingsong Zhang, Mark N. Stein, Yuanfang Xu, Frank A. Seebach, Israel Lowy, Kosalai Kal Mohan, Glenn Kroog, Elizabeth Miller
Journal: Journal of Clinical Oncology (2020)

TPS5592 Background: Bispecific antibodies (bsAbs) are emerging as a protein-based therapeutic strategy for directing T-cell-mediated cytotoxicity in a tumor antigen-specific manner, typically by binding to both tumor antigen and the CD3 receptor on T cells. REGN5678 is a human IgG4-based, first-in-class costimulatory bsAb designed to target prostate tumors by bridging prostate specific membrane antigen expressing tumor cells with the costimulatory receptor, CD28, on T cells, and providing amplified T-cell receptor-CD3 complex-mediated T-cell activation within the tumor through the activation of CD28 signaling. At the tumor site, REGN5678 may synergize with PD-1 inhibitors. In mouse models, REGN5678 in combination with PD-1 antibody has improved anti-tumor activity compared with either therapy alone (Skokos et al CRI/CICON 2019; oral, session 3). This study evaluates the safety and anti-tumor activity of REGN5678 alone and in combination with cemiplimab in patients with metastatic castration-resistant prostate cancer (mCRPC) who progressed after prior therapy. Methods: This is an open label, Phase I/II, first-in-human study evaluating safety, tolerability, pharmacokinetics (PK), and anti-tumor activity of REGN5678 alone and in combination with cemiplimab in treatment-experienced mCRPC (NCT03972657). For inclusion, patients must have received at least two approved therapies for metastatic disease, including a second-generation hormonal agent. REGN5678 is administered weekly and cemiplimab (350 mg) is administered once every 3 weeks. During dose escalation, a 3-week safety lead-in of REGN5678 monotherapy will be administered prior to the addition of cemiplimab. Study therapies are administered until disease progression, intolerable adverse events, withdrawal of consent, or study withdrawal criterion is met. The primary objectives in dose escalation are to evaluate safety, tolerability, and PK of REGN5678 alone and in combination with cemiplimab. Expansion cohort(s) will be enrolled once a REGN5678/cemiplimab recommended Phase II dose is determined. During the expansion phase, the primary trial objective is to assess clinical activity, as measured by objective response rate of REGN5678 in combination with cemiplimab per modified Prostate Cancer Working Group 3 criteria. This study is currently open to enrollment. Clinical trial information: NCT03972657 .
Exploration of residents' choices for first contact care in Beijing communities and influencing factors
Authors: Xue-ying Sun, Jun Yin, Ying-xian Ye, Ying-chao Yang
Journal: BMJ (2012)

A random sample survey was conducted in 17 community medical institutes in 4 districts in Beijing.Among an effective sample of 385 residents.47.5％ (n =183)of community residents chose community medical institutes for first contact care while 52.5％ (n =202) opted for class other hospitals.Residents with lower education levels tended to choose community medical institutes (P =0.01).And those with chronic diseases preferred to choose communities (P=0.00).

Key words: 
Hospitals, community; Factor analysis, statistical
Optimization of screening tools in patients eligible to receive immune-checkpoint inhibitors.
Authors: Lorena Ostios-Garcia, Oliver Higuera, Sara Martinez-Fdez, Alvaro Pinto, Enrique Espinosa, Beatriz Castelo, Patricia Cruz, Paloma Yubero, Jaime Feliu Batlle
Journal: Journal of Clinical Oncology (2020)

e14139 Background: The management of immune-related adverse events (irAEs) produced by immune-checkpoint inhibitors can be challenging, considering differences with the toxicity of classical chemotherapy. In this study, we explored the limitations in the preventions and diagnosis of irAEs at our institution and developed a strategic plan to solve them according to guidelines of the European Society for Medical Oncology and the American Society of Clinical Oncology. Methods: This is a two-phase, single center, exploratory study. In the first phase, we analyzed a random sample of 20 patients (pts) treated with nivolumab or pembrolizumab in the years 2017-2018. A Pareto chart was designed to identify issues in the baseline screening, as well as potential ways to improve the management of irAEs. After that, we implemented corrective measures based on educational lectures, early identification of patients eligible for immunotherapy, standardized protocols, and a profile of screening tests in the electronic medical records. We applied the new strategy on 15 pts treated from January-April 2019. To compare the impact of the implemented measures we used a run chart, frequencies/percentages for categorical variables, and medians/ranges for continuous variables. Adverse events were assessed according to CTCAEv5.0. Results: In the first phase, 38% of the required tests were done before the start of immunotherapy. We identified a deficit in the evaluation of cardiac and pulmonary function, chronic infections, and skin disorders. 45% of pts had some irAEs (15% G1, 15% G2 and 15% G3). Due to toxicity, 33% of pts had delays in the administration of treatment, and 11% required early interruption. After applying corrective measures, 81% of tests were requested before treatment initiation. However, screening for tuberculosis infection and echocardiogram continued to be deficient. We identified irAEs in 53% of pts (16% G1, 50% G2 and 25% G3), and 37% of them presented two or more different irAEs during the period of treatment. 37,5% and 12,5% of pts had delays or early interruption of immunotherapy, respectively. All of pts with irAEs had presented any basal alterations in screening tests. The most frequent basal alterations were found in pancreatic (66%) and thyroid activity (50%). Conclusions: Simple improvement strategies such as education programs, standardized protocols, and an electronic profile can improve the basal screening for potential irAEs. The basal alterations found in some pts can be related to the development of side effects or interactions with the immunotherapy.
甲状腺功能减退性肌病一例
Authors: 赵霞
Journal: BMJ (2005)

患者男,75岁.言语笨拙,反应迟钝,皮肤干燥,毛发稀疏,全身水肿.四肢肌肉肥大、质硬.肌电图示肌源性损害,肌活检示Ⅰ型肌纤维肥大,Ⅱ型肌纤维萎缩,超微结构可见肌丝变性,Z线水纹状,脂褐质累积,线粒体轻度变性.三碘甲状腺原氨酸(T3)＜0.8 pmol/L,甲状腺素(T4)＜0.67 pmol/L,天冬氨酸氨基转移酶(AST) 97 U/L,丙氨酸氨基转移酶(ALT) 43 U/L,乳酸脱氢酶(LDH) 662 U/L,肌酸激酶(CK) 5 209 U/L.诊为甲状腺功能减退性肌病,采用左旋甲状腺素片治疗,开始50 μg/d,逐渐加量,30 d后肌病症状好转,90 d后症状消失。
Face masks in the covid-19 crisis: caveats, limits, and priorities
Authors: John D Middleton, Henrique Lopes
Journal: BMJ (2020)

We agree with Greenhalgh and colleagues that decision making should be based on scientific knowledge, but when knowledge is incomplete, as in the current pandemic, judgments based on precaution and pragmatism become increasingly necessary.1 The Association of Schools of Public Health in the European Region’s report launched on 24 April recommends the use of face masks by the general public, with clear caveats, limits, and priorities.2

Non-medical grade …
Utilization of imaging and outcomes of care among metastatic colorectal cancer (mCRC) patients (pts) receiving bevacizumab containing regimens.
Authors: Afsaneh Barzi, Hanke Zheng, Jeffrey McCombs
Journal: Journal of Clinical Oncology (2020)

e14011 Background: Chemotherapy combined with bevacizumab is the most commonly used treatment first line therapy in pts with mCRC. Decisions for continuation or change of chemotherapy are based on the findings of CT scan, the most commonly used from of imaging in this population. Modeled after clinical trials, CT scan every 2 months is adopted as a standard of care. Yet, patterns of utilization of CT scan in general population is unknown. We set to explore CT scan utilization and associated outcomes among pts with mCRC. Methods: The De-identified Clinformatics Data Mart (OptumInsight, Eden Prairie, MN) covering January 2008 to December 2016 was used for this analysis. Pts with two out-patient and/or one in-patient ICD codes for colorectal cancer were identified. Pts with at least 180 days of enrollment, no chemotherapy within 120 days prior to chemotherapy, and at least one claim for CT scan were eligible for analysis. Recipients of FOLFOX (CAPOX) or FOLFIRI (XILIRI) +bevacizumab were identified using HCPCS codes and the data of their 1 st treatment was registered as index date. The primary endpoint of the analysis was exposure to both FOLFIRI and FOLFOX, secondary endpoint was survival. SAS software was used for data processing and analysis. Results: A total of 3261 pts met the inclusion criteria 78% with oxaliplatin based regimens and 22% with irinotecan regimens. The median age of the population is 66 (19-89), and 58.3% of the identified pts were male. The median duration of first line therapy was 119 days. Median number of CT scan during first line was 2.3. The median and mean number of CT scan per 2 months were 0.82 and 0.94. There was no difference in age, gender, and comorbidities in those with less than 2 vs. 2 or more CT scans. Exposure to both regimens (measured with switching from one regimen to another) was 35% in pts with less than 2 CT scans and 44% in those with 2 or more CT scan (p-value &lt; 0.0001). Probability of survival at 12 months was 83% for all patients regardless of the frequency of scans. Conclusions: In patients with mCRC more frequent scans is associated with higher probability of access to active agents. However, survival probability at 12 months was not different between the two groups.
浙江省城市社区卫生服务政策分析
Authors: 叶真, 周爱珍, 石文军, 顾亚明
Journal: BMJ (2007)

卫生服务系统以人群健康为系统目标,包括3个基本要素:组织结构、管理制度和外部环境,制度环境是城市社区卫生服务的重要组成部分.2006年2月,《国务院关于贯彻城市社区卫生服务的指导意见》(简称《指导意见》)和国家7个部(委、局)的9个配套文件为浙江省出台配套政策提出了要求和依据.因此,开展浙江省城市社区卫生服务政策分析,有助于出台针对性的配套政策,近而探讨与组织结构和外部环境相适应的一系列宏、微观管理制度(或运行机制),兼顾需方、供方和政府三者利益,使总效益最大化。
Survival in metastatic renal cell carcinoma (mRCC) patients over two decades: Does age mater?
Authors: Hendik Eggers, Christoph Schuenemann, Viktor Grünwald, Linda Rudolph, Maria-Luisa Tiemann, Christoph W. Reuter, Arnold Ganser, Philipp Ivanyi
Journal: Journal of Clinical Oncology (2020)

e17103 Background: Although the therapeutic landscape changed dramatically in the recent past, little is known about the outcome of elderly mRCC patients, a cohort underreported in clinical trials. Therefore, this analysis addresses changes in OS between treatment periods and age. Methods: mRCC patients treated at Hannover Medical School from 01/2003 - 12/2018 were retrospectively identified. Treatment periods were defined from 01.01.2003–31.12.2009 (P1) and 01.01.2010 –31.12.2018 (P2). Age groups were defined according to WHO (age≤60 years = not old, age 60-75 = older, age ≥76 = old). Descriptive statistics, Kaplan-Meier analysis and logistic regression were applied. Results: Overall, 314 patients showed a median OS of 39.7 (95%-CI: 33.1-46.3) months. Median OS is significantly longer for patients treated in period two (P1 vs. P2: 59.1 vs. 35.1(HR 0.64, 95%-CI 0.48-0.86) months. Median OS increase in median OS between treatment periods was shown within all age groups and was most apparent in the old patients (P1 vs. P2; not old, 35.1 vs. 68.9 months (HR 0.71, 95%-CI 0.45-1.13); older 40.1 vs. 59.1 months (HR 0.62 (95%-CI 0.40-0.97); old 18.8 vs. 45.7 months, (HR 0.43, 95%-CI 0.18-1.05). Conclusions: This observed increase in OS between treatment periods might reflect the advance of therapeutic options. Interestingly, the OS increase throughout treatment periods was independent of age subgroups. Although data need further analyzes, currently it can be hypothesized, that age should not council utilization of therapeutic armamentarium in mRCC.
Website of the week: Drugs for Alzheimer's disease
Authors: T Jackson
Journal: BMJ (2000)

Searching on the internet for impartial professional information about drugs to treat Alzheimer's disease, indeed any drugs, can be tricky. Key in “Alzheimer's,” and you are confronted with 286 000 pages (and rapidly rising). Key in the drug name, even the generic name, and you have to dissociate the information from drug company advertising and sponsorship. With a fairly new …
Plasma levels of N-terminal pro-B-type natriuretic peptide in patients with metabolic syndrome
Authors: Yuan-yuan Bao, Li-nuo Zhou, Ren-ming Hu, Wei-wei Zhang, Wei Ding
Journal: BMJ (2011)

A retrospective analysis was made on clinical data of 230 cases of metabolic syndrome (MS) and 239 cases of non-MS admitted to department of cardiology and endocrinology of Huashan Hospital from July 2005 to August 2009.Multiple linear regression analysis was performed to assess the association between levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and potential influencing factors.Covariance analysis was used for group comparison.Multiple linear regression analysis demonstrated that age,body mass index,systolic blood pressure,diastolic blood pressure,insulin resistance index,triglyceride,low density lipoprotein-cholesterol,creatine,left atrial diameter,left ventricular posterior wall dimensions,left ventricular ejection fraction were independent predictors for plasma levels of NT-proBNP in those subjects(P ＜ 0.05).Covariance analysis showed that plasma levels of NT-proBNP in MS group were significantly lower than those in non-MS group ( P ＜ 0.05).Further analysis found that plasma levels of NT-proBNP in MS patients with high triglyceride and body mass index,but normal systolic and diastolic blood pressure,normal fasting plasma glucose were significantly lower than those in non-MS group ( P ＜ 0.05 ).The results indicate that decreased plasma levels of NT-proBNP might be related to lipids disorder and obesity of MS patients.

Key words: 
Metabolic syndrome X; N-Terminal Pro-B-Type Natriuretic peptide
An investigation on use of aspirin in cardiac outpatients
Authors: 张涓, 万昕红, 杨新春, 丁枭伟, 闫慧
Journal: BMJ (2005)

目的 调查阿司匹林在心内科门诊的使用情况,分析其临床应用现状.方法在心内科门诊随机抽取100例正在服用阿司匹林的患者,调查其阿司匹林的使用剂量,分析用量不足的各种原因.结果在100例患者中,54.0%(54/100)患者剂量不恰当;其中,78例未曾住院的门诊随访的患者中,64.1%(50/78)剂量过低;而22例出院后门诊随访的患者中,22.7%(5/22)患者剂量过低.阿司匹林使用剂量不恰当的主要原因为:患者担心不良反应;非心内专科医生指导错误;门诊医生随访中忽略询问使用情况.结论尽管阿司匹林已广泛应用于心血管疾病的一级预防和二级预防,但却普遍存在使用剂量过低的情况。
Comprehensive analysis of HER2 status through genomic, transcription, and translation among 5,305 patients with diverse malignancies.
Authors: Akram Mesleh Shayeb, Razelle Kurzrock, Shumei Kato
Journal: Journal of Clinical Oncology (2020)

3632 Background: HER2 alterations is a predictive biomarker for anti-HER2 regimen. Success in breast and gastric cancers with anti-HER2 therapies translated to explore their efficacy in other tumors. Currently, measurement of HER2 can be done by assessing the expression of protein [e.g. immunohistochemistry (IHC)] or gene amplification of copy number variation (CNV) [e.g. fluorescence in situ hybridization or next-generation sequencing (NGS)]. But little is known about the transcription level (mRNA) of HER2. Herein, we investigated HER2 mRNA expression and its association with gene and protein expressions among diverse cancer types. Methods: Between 2015-2019, HER2 status was evaluated using IHC, qRT-PCR and NGS by Paradigm Diagnostics (CLIA-certified laboratory). All tumors in the database were included for analysis. Correlations between all 3 tests were done. An illustrative patient who was treated with anti-HER2 therapy base on the mRNA testing is presented. Results: HER2 testing was performed on 5305 patients (pts) with diverse cancers including NSCLC (n=1175), breast (n=1040) and colon (n=566); 4.1% (161/3926) had amplification through NGS, 33.3% (615/1848) had mRNA overexpression and 9.3% (236/2533) had overexpression by IHC. Of 723 pts who had all three tests performed, we found 7.5% (54/723) of pts with all three HER2 markers being positive (CNV [+]/mRNA [+]/ IHC [+]). Meanwhile, variety of amplification/ expression patterns were seen (see Table). CNV positivity translated to protein expression in 95% of cases. While only 4% of pts were IHC positive when CNV and mRNA were negative. 20% (144/723) of pts had mRNA overexpression alone among diverse cancer types. Representative case of 70yo female with metastatic cholangiocarcinoma harboring mRNA overexpression (but negative for CNV, IHC unclear due to sample insufficiency) who had near complete response to anti-HER2 therapy with progression-free survival of 24+ months is presented. Conclusions: HER2 status can be discordant with different assays but NGS positivity has excellent correlation with mRNA and protein expression. Of importance, HER2 mRNA can be overexpressed in 20% of pts even when gene amplification and protein expression are negative. Further studies are warranted to determine the clinical utility of mRNA as a biomarker for HER2 and potential use for anti-HER2 targeted therapies. [Table: see text]
评分者培训及其在医学考核中的应用
Authors: 顾杰, 黄俏雯, 祝墡珠
Journal: BMJ (2012)

评分者培训是对评分人员进行针对性训练以提高评分准确性的一系列方法的总称.常用方法包括评分者误差培训法、绩效维度培训法、参照系培训法和行为观察培训法.在全科师资中开展评分者培训研究具有重要的现实意义。
Evaluation of high-dose methotrexate serum concentration requirement for discharge.
Authors: Amulya Yellala, Prajwal Dhakal, Brooke Deason, Susanne Liewer, Avyakta Kallam, Matthew Alexander Lunning, Philip Jay Bierman, Julie Vose, Gregory Bociek
Journal: Journal of Clinical Oncology (2020)

e19204 Background: Methotrexate (MTX) is used in high doses for the treatment of ALL, lymphoma, and metastatic breast cancer with CNS involvement. To avoid drug accumulation and mitigate toxicities caused by delayed clearance, patients (pts) are usually admitted to the hospital and standard supportive care with IV hydration, urinary alkalization, and leucovorin is provided and adjusted based on daily levels. Historically, a serum methotrexate level ≤ 0.05 µmol/L has been used to declare clearance and an ideal level for discharge based on studies conducted in the 1970s. We conducted a retrospective review in 2018 to identify frequency of supportive dose escalations required with MTX levels &gt; 0.05 µmol/L. In 69 pts, 4 patients demonstrated delayed renal clearance and required supportive care escalations but all occurred at MTX levels &gt; 0.3 µmol/L. This led to a proposed pilot discharge process once MTX was &lt; 0.3 µmol/L to confirm the safety of earlier discharge. Methods: A retrospective chart review of pts with baseline CrCl ≥60 who received HD MTX between 07/2018 – 08/2019. Data collection included diagnosis, MTX discharge level, supportive care at discharge including PO Leucovorin and PO sodium bicarbonate and number of days supply, post-discharge complications (AKI, mucositis, fever, others). Primary outcome was the number of patients who required inpatient or outpatient supportive care for acute complications after being discharged with a methotrexate level ≥ 0.1 µmol/L. Descriptive statistics were used. Results: A total of 41 pts were included. Median age was 55 yrs (32-78), 25% were male. 73% were treated for DLBCL, median dose of MTX was 3500 mg/m2. Median MTX level at the time of discharge was 0.16 µmol/L (0.1-0.3 µmol/L). 12 pts were discharged with PO Leucovorin and 15 pts were discharged with both Leucovorin and PO Sodium bicarbonate with an average of 2 day’s supply. 1 acute complication of neutropenic fever requiring admission for inpatient antibiotics occurred which was felt to be unrelated to MTX level at discharge. Conclusions: This pilot suggests that pts can be safely discharged with MTX levels upto 0.3 µmol/L without acute complications. Results of this study will be used to a develop a standardized protocol outlining criteria for early discharge in select pts with MTX levels &lt; 0.3 µmol/L to reduce length of stay, cost of hospitalization and improve patient satisfaction. [Table: see text]
儿童颊部放线菌病一例
Authors: 刘红
Journal: BMJ (2006)

患儿女,8岁.无明显诱因左颊部反复肿胀疼痛4个月,呈弥漫性肿胀,质地硬,无发热,曾静脉滴注青霉素G 640万单位/d共5 d、先锋霉素V 2.0g/d共10 d,好转.近10 d又出现肿胀、疼痛,门诊以左颊部感染待查收入院.患儿无发热史.体格检查:体温36.8℃,脉搏88次/min,呼吸22次/min,血压98/65 mm Hg(13.0/8.6 kPa),营养不良貌,左颊部肿胀,压疼,界限清,约1.5 cm×2 cm有波动感.心肺无异常,腹平软.饮食差,大、小便正常.结核菌素试验阴性;白细胞7.1×109/L,中性粒细胞0.6,淋巴细胞0.4,血红蛋白120g/L,红细胞4.5×1012/L;红细胞沉降率12 mm/1 h.切开引流,见硫磺颗粒与脓液一同流出,涂片检查:革兰染色阳性,见放射状菌丝.刮除脓腔内肉芽组织,送病理学检查,结果:(颊部)放线菌病.给予青霉素640万单位/d,静脉滴注共15 d,之后青霉素160万单位,肌肉注射2次/d共20 d.随访1年,未复发。
Nine weeks versus six months of adjuvant trastuzumab in HER2-positive breast cancer: 3-year disease-free survival results.
Authors: Maher Saifo
Journal: Journal of Clinical Oncology (2020)

e12530 Background: A total of 12 months adjuvant trastuzumab is still the optimal choice for patients with HER2-positive early breast cancer. However, the shorter course of 9 weeks may be considered as a cost-effective and safe option in developing countries such as Syria. Purpose: We aimed at investigating whether short-course 9-week adjuvant Trastuzumab is non-inferior to 6-month treatment at Albairouni University Cancer Center. The primary endpoint was disease-free survival (DFS). The secondary objective was assessing toxicities, especially cardiotoxicity. Methods: Patients with HER2-positive stage I-IIIC breast cancer were assigned to receive either 9 weeks or 6 months of trastuzumab in combination with adjuvant chemotherapies (sequentially). The 9-week group; 90 patients received trastuzumab intravenously (loading dose 4 mg/kg; then 2mg/kg weekly), whereas in the 6-month group; 157 patients, trastuzumab was delivered every 3 weeks intravenously (loading dose 8 mg/kg then 6 mg/kg). The LVEF was measured pretreatment and every 3 months afterwards. Results: 3-year DFS was 71.87% in the 9-week group versus 76.43% in the 6-month group, (Non-significant). No obvious side effects have been noticed during the follow-up period in the 9-week group. Congestive heart failure was reported in 2.55% of patients in the 6-month group. Conclusions: Short-course 9-week adjuvant trastuzumab is less effective than 6 months of treatment, with less cardiotoxicity. The short course could be considered in patients with heart disease and low risk of recurrence.