tbuckley/cabot-search huggingface dataset:
Assessment and management of cardiovascular risk factors among U.S. Veterans with newly diagnosed prostate cancer.
Authors: Lova Sun, Ravi Bharat Parikh, Kyle William Robinson, Samuel U Takvorian, David J. Vaughn, Vivek Narayan, Bonnie Ky
Journal: Journal of Clinical Oncology (2020)

5510 Background: Cardiovascular disease (CVD) is a leading cause of death in men with prostate cancer (PC). Androgen deprivation therapy (ADT) is associated with increased CVD risk, and American Heart Association guidelines recommend CVD risk factor assessment and management in PC patients starting ADT. We characterized rates of guideline-concordant assessment and management of CVD risk factors for US Veterans with newly diagnosed PC, according to ADT use and prior atherosclerotic CVD diagnosis. Methods: We used cross-sectional data from VA Corporate Data Warehouse to identify Veterans with an incident diagnosis of PC from 2001-2017. Primary outcomes were guideline-concordant baseline CVD risk factor assessment (defined as ≥1 blood pressure, cholesterol, and HbA1c or fasting glucose measurement within 1 year prior to 6 months after ADT start or PC diagnosis), CVD risk factor control, and CVD risk-reducing medication use. Risk difference multivariable regression analyses adjusting for age, race, poverty, PC risk category, and year were used to evaluate the effect of ADT on study outcomes. Results: Of 191,829 Veterans with newly diagnosed PC, 27% (n = 51,419) were treated with ADT within 1 year of diagnosis, and 18% (n = 34,110) had a pre-existing diagnosis of atherosclerotic CVD. From 2001-2017, annual rates of guideline-concordant CVD risk factor assessment increased from 26% to 77%. In adjusted analyses, pre-existing atherosclerotic CVD diagnosis was associated with higher CVD risk factor assessment rate (64% vs 53%), better control of baseline LDL (94 vs 108 mg/dL), and higher rates of anti-hypertensive (90% vs 66%), lipid-lowering (83% vs 49%), and glucose-lowering (32% vs 20%) medication use. Treatment with ADT was associated with similar to minimally higher rates of CVD risk factor assessment (58% vs 54%), LDL control (104 vs 105 mg/dL), and anti-hypertensive (73% vs 69%), lipid-lowering (55% vs 55%), and glucose-lowering (25% vs 21%) medication use. Sixty percent of men starting ADT had at least one sub-optimally controlled CVD risk factor, and 1 in 4 of these men were not receiving a corresponding risk-reducing medication. One third of men starting ADT had BMI &gt; 30 kg/m2. Conclusions: CVD risk factor assessment in Veterans with PC has increased over time. However, ADT does not appear to meaningfully impact CVD assessment or management, despite its known association with CVD risk. Over half of patients initiating ADT had elevated CVD risk factor(s). Multi-disciplinary efforts to improve CVD risk mitigation are needed among men initiating ADT.
A phase I/II, two-part, multicenter, first-in-human study of DS-7300a in patients with advanced solid malignant tumors.
Authors: Johanna C. Bendell, Toshihiko Doi, Manish R. Patel, Sarina Anne Piha-Paul, Shiraj Sen, Toshio Shimizu, Ben Cheng, Sabeen F. Mekan, Yusuke Myobatake, Yasuyuki Okuda, Gul Serbest, Melissa Lynne Johnson
Journal: Journal of Clinical Oncology (2020)

TPS3646 Background: B7 homologue 3 (B7-H3) is a protein that is overexpressed in various cancer types, including lung, head and neck squamous cell carcinoma, prostate, esophageal, and breast. B7-H3 overexpression is associated with poor prognosis because it promotes increased invasive and metastatic potential of cancer cells (Dong P, et al. Front Oncol. 2018;8:264). Currently, no B7-H3–targeted cancer therapies are approved. DS-7300a is an antibody-drug conjugate composed of a humanized anti–B7-H3 IgG1 monoclonal antibody (MABX-9001a) conjugated to a drug linker that releases its payload upon internalization by cancer cells. The payload, DXd, is an exatecan derivative that inhibits topoisomerase I, an enzyme that relaxes supercoiled DNA for replication and transcription. DS-7300a induced apoptosis in cancer cells in vitro and showed potent antitumor activity in xenograft models of various types of solid tumors in vivo. Methods: This phase 1/2, multicenter, nonrandomized, open-label, first-in-human study of DS-7300a is ongoing in the United States and Japan in patients with selected advanced solid tumors (NCT04145622). This study has 2 parts: dose escalation (part 1) and dose expansion (part 2). Primary objectives are to evaluate the safety, tolerability, and antitumor activity of DS-7300a and to determine the maximum tolerated dose or recommended dose for the expansion part. Secondary objectives include the pharmacokinetic characterization of DS-7300a, determination of the total levels of anti–B7-H3 antibody and the drug component (DXd), and assessment of the incidence of anti-drug antibodies against DS-7300a. Key inclusion criteria are age ≥ 18 years (United States) or ≥ 20 years (Japan), an ECOG performance status of 0 or 1, ≥ 1 measurable lesion according to RECIST 1.1 as assessed by the investigator, and consent to provide pre- and on-treatment tissue samples (mandatory if clinically allowed and not contraindicated). Key exclusion criteria include prior treatment with orlotamab, enoblituzumab, other B7-H3–targeted agents, or an antibody-drug conjugate that is conjugated with a topoisomerase I inhibitor. Dose expansion will start with 3 cohorts, including patients with selected advanced solid tumors. In both parts, DS-7300a will be administered intravenously on day 1 of each 21-day cycle. During dose escalation, the starting dose of DS-7300a is 0.8 mg/kg. This trial is currently in the dose-escalation part. Clinical trial information: NCT04145622 .
全科医师社区精神卫生服务继续医学教育探讨
Authors: 甘一方
Journal: BMJ (2006)

自20世纪60年代以来,在欧美等发达国家精神疾病的管理模式已从传统的医院模式转向社区精神卫生服务模式,这种新的管理模式不仅有利于精神病患者的巩固维持康复治疗,有利于他们回归社会,更有利于不断提升社区整体人群的心理健康水平并预防精神疾病的发生,同时也可以合理使用医疗资源,大幅度的降低医疗成本,这是一种有效而经济的管理模式。
Sequential monitoring of circulating stromal cells from blood is predictive of progression in NSCLC patients undergoing anti-PD-L1 therapy after definitive chemoradiation therapy.
Authors: Daniel Adams, Alexander Augustyn, Jianzhong He, Yawei Qiao, Ting Xu, Zhongxing X. Liao, Kirby P Gardner, Amama Ali, Daniel J Gironda, Cha-Mei Tang, Steven H. Lin
Journal: Journal of Clinical Oncology (2020)

3051 Background: Cancer Associated Macrophage-Like cells (CAMLs) are a recently described circulating stromal cell common in the peripheral blood of patients with solid tumors. In non-small cell lung carcinoma (NSCLC), patients with CAMLs ≥50µm after completion of chemoradiation therapy (CRT) have been shown to have worse progression free survival (PFS). However, with the recent addition of anti-PD-L1 therapies in conjunction with CRT as standard of care, it has never yet to be evaluated whether CAMLs remain predictive for monitoring progression in NSCLC patients post anti-PD-L1 therapy. Methods: A 2 year single blind prospective study was undertaken to test the relationship of ≥50µm CAMLs to PFS based on imaging in lung patients before and after induction of CRT and PD-L1. We recruited 104 patients with pathologically confirmed unresectable NSCLC Stage II (n = 14), Stage III (n = 83), Stage IV (n = 3), and locally recurrent disease (n = 4). Baseline (BL) blood samples were taken prior to start of therapy. A second time point blood sample (T1) was taken at the end of radiotherapy (~40 days). A third time blood sample (T2) was taken after induction of anti-PD-L1 therapy (e.g. Imfinizi, Keytruda, etc.). Blood was filtered by CellSieve filtration and CAMLs were quantified. Analysis by CAML size of &lt; 49 µm or ≥50 µm was used to evaluate PFS hazard ratios (HRs) by censored univariate &amp; multivariate analysis. Results: CAMLs were found in 87% of samples averaging 2.9 CAMLs/7.5mL sample. At BL, CAMLs ≥50 µm had similar PFS to patients with &lt; 50 µm CAMLs (HR = 1.1 95%CI 0.6-1.95 p = 0.8661). However, after CRT (T1), patients with CAML size ≥50 µm had worse PFS (HR = 3.2, 95%CI 1.8-5.8 p = 0.0002). After induction of anti-PD-L1 therapy (T2), patients with ≥50 µm CAMLs also had worse PFS (HR = 2.8 95%CI 1.5-5.4 p = 0.0037). CAML size at BL was not accurate at predicting progression within 24 months; however ≥50 µm CAMLs after CRT or after 1 cycle of anti-PDL1 therapy was 71% accurate at predicting progression of disease. Conclusions: Our data suggests that in NSCLC, ≥50 µm CAMLs after completion of CRT or appearing after induction of anti-PD-L1 therapy appears to predict progressive disease. If validated, additional studies are needed to determine if CAMLs can serve as a significantly prognostic blood based marker for predicting survival in NSCLC patients early in the treatment regime.
脑卒中后吞咽困难患者经鼻空肠管肠内营养治疗观察
Authors: 李瑞红, 李德春, 李洁, 胡献礼
Journal: BMJ (2008)

脑卒中患者常伴有严重的意识障碍和吞咽困难,存在营养不良的风险,影响疾病的预后.鼻胃管饲是临床上脑卒中患者常用的肠内营养途径,但常有反流、误吸、吸入性肺炎等并发症,导致喂养受阻.我院对32例脑卒中后吞咽困难患者采用经鼻空肠管肠内营养,临床效果良好,报道如下。
内分泌科临床精粹(三)
Authors: 李乃适, 潘慧
Journal: BMJ (2010)

一、诊断身材矮小的目的和方法[1] 诊断身材矮小并非为了设法让每个人的身高接近姚明,而是首先判断患儿有无器质性疾病.诊断身材矮小的标准是身高位于同年龄、同性别、同种族人群身高的第三百分位以下.身高低于第3百分位,需要检查身材矮小的原因.常见有甲状腺功能减退症、生长激素缺乏症、特纳综合征等.另一个需要关注的问题是是否还有长高的可能,也即看骨龄片上骨骺闭合的程度。
Paclitaxel protein bound (A) plus gemcitabine (G) plus cisplatin (C), and paricalcitol (P)neoadjuvant therapy for localized pancreatic ductal adenocarcinoma (PDAC).
Authors: Erkut Hasan Borazanci, Gayle S. Jameson, Courtney Edwards Snyder, Frank Yung-Chin Tsai, Michael S. Gordon, Sunil Sharma, Carol Guarnieri, Amar Thosani, Syed Rahmanuddin, Ronald Lee Korn, Steven Sckolnik, Sharon Salontai, Rachel Wyman, Susan Haag, Kevin Gosselin, Daniel D. Von Hoff, Albert Amini
Journal: Journal of Clinical Oncology (2020)

4631 Background: Localized PDAC management has recently evolved. Due to concerns over micro metastases at diagnosis the use of neoadjuvant chemotherapy for PDAC has become more common. Typical therapies involve the use of multiagent systemic chemotherapies with or without radiation therapy. In retrospective studies, Cancer Antigen 19-9 (CA 19-9) normalization in borderline resectable (BR) and locally advanced (LA) PDAC has been associated with greater OS. The addition of cisplatin (C) to gemcitabine (G) and paclitaxel protein bound (A), has shown promising clinical data in a previously reported study in advanced PDAC [JAMA Oncol. 2020;6(1):125-132]. We conducted a prospective, phase 2 clinical trial of patients with resectable (R), BR, and LA PDAC utilizing a regimen combining A + G + C + paricalcitol (P) with the primary endpoint of CA 19-9 normalization (NCT03138720). Methods: Eligibility criteria include patients with histologically confirmed R, BR, or LA PDAC, elevated CA 19-9, and a KPS ≥ 70% with normal end organ function. Doses are A 125 mg/m2, G 1000 mg/m2, C 25 mg/ m2, P at a fixed dose of 25 µg on days 1, 8 of a 21-day cycle (all treatment IV). Primary objective is to evaluate CA 19-9 normalization with the neoadjuvant chemotherapy. Secondary objectives are to assess R0 rate, pathologic complete response (pCR), safety and tolerability, radiologic response rate, and 2 year overall survival (OS) from date of study entry. Exploratory objectives include evaluating imaging biomarkers and vascular involvement by tumor in relation to therapy. Results: To date 24 of the planned 24 patients have been enrolled. 13 male, 11 female; age range 49 to 84 yo. Patient classifications is 8 R; 7 BR; 9 LAPC. Median baseline CA 19-9 156 (range 45-3674). Most common drug related grade (gr) 3-4 adverse events (AEs) are: thrombocytopenia gr 3 29%, gr 4 25%, anemia gr 3 45.8%, gr 4 4.2%, and hypophosphatemia gr 3 8.3%. CA 19-9 normalization occurred in 50% (12/24) who have completed at least 1 cycle of treatment. To date, 14 individuals went to surgery, with 13/14 achieving R0, (1 pCR). Overall response rate in measurable patients is 38% (1 CR, 8 PR). Median OS and 2-year survival data are not yet matured. Conclusions: In patients with non-metastatic PDAC, the use of A+G+C+P resulted in a CA 19-9 normalization rate in 50% of individuals. The study is ongoing and OS data is maturing. Clinical trial information: NCT03138720 .
Clinical analysis for 51 cases of primary hyperparathyroidism
Authors: Zhi-min Huang, Guo-hong Wei, Hai-peng Xiao, Yan-bing Li
Journal: BMJ (2011)

Objective To study clinical characteristics,causes of misdignosis and diagnostic and therapeutic methods for primary hyperparathyroidism (PHPT).Methods Retrospective analysis was done for 51 patients of PHPT,47 confirmed by biopsy after surgical operation and 4 without operation diagnosed based on their serum levels of calcium,alkaline phosphatase ( ALP),intact parathyroid hormone ( iPTH ),and computed tomography (CT) or 99mtechnetium sestamibi (99mTcMIB1) imaging at the First Affiliated Hospital of Sun Yat-sen University,Guangzhou during June 1997 to November 2010.Results Bone-related complications were the most common clinical manifestation,accounting for 51％ (26/51 ) of the cases,and adenoma,a benign,enlarged and hyperactive parathyroid gland,in 34 of 47 cases ( 72％ ).In orthotopic lesions,the right inferior was affected in 19 of 46 cases (41％),followed by the left inferior in 13 cases (28％),while 5 of 51 cases (10％) with ectopic parathyroid gland.PHPT was easily misdiagnosed as urolithiasis,rheumatic disease,primary osteoporosis,etc,accounting for 92％ of the cases in our study.Preoperative serum levels of calcium,ALP and iPTH in the patients varied with their clinical type and pathological classification,the highest in patients with urolithiasis-bone-related complications [ (3.22 ±0.35) mmol/L,(1455 ± 1091 ) U/L and (1669 ± 515 ) ng/L,respectively ] and in patients with parathyroid carcinoma [ (3.46 ± 0.40) mmol/L,( 1410 ± 426) U/L and ( 1861 ± 768) ng/L,respectively ].Sensibility of preoperative localization diagnosis using ultrasonography,CT and 99mTcMIBI was 88％ (35/40),97％ (30/31) and 97％ (31/32),respectively.Conclusions PHPT is frequently misdiagnosed as other diseases.Measurement of serum calcium should be included in routine physical examinations,supplemented with measurement of serum ALP and iPTH,as well as medical imaging,which can help avoid misdiagnosis.CT combined with 99mTcMIBI imaging can improve accuracy of preoperative localization diagnosis.

Key words: 
Hyperparathyroidism, primary ( PHPT ) ; Diagnostic technique; Endocrine disease; Diagnosis, differential; Treatment
Community management of asymptomatic hyperuricemic patients
Authors: Jie Chen
Journal: BMJ (2017)

Objective
To evaluate the efficacy of community management of asymptomatic hyperuricemic patients.


Methods
Two hundred and six patients with asymptomatic hyperuricemia in Yuetan community of Beijing were randomly and equally divided into study group and control group. Patients in study group received 12-month standardized management, while those in control group were given conventional management. After 12 months of intervention, the clinical data and related information were analyzed and the effect of intervention was evaluated by questionnaire survey.


Results
After 12-month intervention, the rates of unhealthy lifestyle in intervention group were significantly lower, and the exercise time was significantly more than those in control group [drinking: frequently 8.7%(9/103)vs. 11.7%(12/103), seldom 83.5% (86/103) vs. 68.9% (71/103), χ2=7.005, P=0.030; eating animal offal: seldom 88.4%(91/103) vs. 76.7%(79/103), frequently 1.9%(2/103) vs. 8.7%(9/103), χ2=6.302, P=0.043; eating seafood: seldom 74.8%(77/103) vs. 52.4%(54/103), frequently 4.8%(5/103) vs. 16.5%(17/103), χ2=12.867, P=0.002; eating thickened gravy: seldom 78.6%(81/103)vs. 53.4%(55/103), frequently 2.9%(3/103) vs. 13.6%(14/103), χ2=16.334, P=0.000; exercise time: seldom 17.5%(18/103)vs. 24.3%(25/103), 1-3 h 26.2%(27/103) vs. 38.8%(40/103), 4-6 h 32.0% (33/103) vs. 20.4%(21/103), ≥7 h 24.3%(25/103) vs. 16.5%(17/103), χ2=7.852, P=0.049]. The blood uric [(403±54) vs. (474±71) μmol/L], cholesterol [(4.6±0.8) vs.(4.9±1.0)mmol/L], triglyceride[(1.65± 0.54) vs. (1.86±0.86) mmol/L] and systolic pressure [(128±10) vs. (131±14) mmHg(1 mmHg=0.133 kPa)] in intervention group significantly lower than those in control group (t=7.984, P=0.000; t=2.803, P=0.006; t=2.130, P=0.034; t=2.059, P=0.041). The awareness rate of hyperuricemia-related knowledge in intervention group was significantly higher than that in control group [85.1% (964/1 133) vs. 45.5%(516/1 133), χ2=390.959, P=0.000].


Conclusion
Standardized community management is effective for patients with asymptomatic hyperuricemia.


Key words: 
Hyperuricemia; Disease management; Intervention studies; Questionnaires
Explorative analysis of expanded access for intermediate-size and larger patient populations.
Authors: Andriy Krendyukov
Journal: Journal of Clinical Oncology (2020)

e19070 Background: Cancer is a major public health problem worldwide and is the second leading cause of death in the USA. While continuous efforts are being made by the US Food and Drug Administration to bring more new oncology products (NOP) to patients, there is a high unmet medical need for oncology patients to get access to care, and in particular access to NOP outside of clinical trials before the NOP is approved or commercialized. To improve access to NOP, several pathways are endorsed by competent authorities including: early dialogue with regulatory agencies; accelerated assessments; conditional marketing authorization; and early access provision, known as expanded access (EA) in the USA and compassionate use (CU) in the EU. Methods: A literature search and explorative analysis of available EA data from Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER) relating to submission and approval of existing or investigational new drugs (IND) was performed for individual (single) patient emergency and non-emergency IND (IPIND), intermediate size IND (ISIND), and treatment IND (TIND). The findings were compared to centralized CU programs. The analysis was primarily focused on understanding the current landscape of EA for patient groups compared with individual patient categories. Results: Based on available CDER and CBER data submissions for ISIND and TIND categories were dramatically low compared with IPIND and total applications for EA: 1.25% (ISIND) and 0.13% (TIND) out of 1,598 EA applications received in 2018; and respectively 2.7% and 0.11% out of 1,741 EA applications in 2017; 2.6% and 0.24% out of 1,634 EA applications in 2016; 3.6% and 0.15% out of 1,328 EA applications in 2015; and 2.8% and 0.05% out of 1,886 EA applications in 2014. A high approval rate was reported for all three EA categories, and in particular approval of 95% (174 out 183) for ISIND and 100% (1 application) for TIND by CDER, and approval of 89% (24 out of 27) for ISIND and 80% (8 out of 10) for TIND by CBER. No applications for CU were reported by the European Medicines Agency for the same period of time, however several oncological products have been approved for CU in some European countries. Conclusions: Despite high approval rates, applications for ISIND and TIND remain low, especially in comparison to IPIND. In the absence of, or limited, alternative treatments, access provision to patient groups such as ISIND and TIND in the USA, and CU in the European Union, might represent an underutilized opportunity for oncological patients to obtain early access to care.
Training general practitioners in hypertension management with expert-guided network tracing system
Authors: 徐小玲, 唐新华, 严静, 俞蔚, 章一丰, 方顺源, 罗建勇, 金宏义
Journal: BMJ (2012)

Objective To evaluate the application of “expert-guided network tracking system” in training community general practitioner for hypertension management.Methods Total 855 general practitioners (GPs) from 20 community health service centers in Hangzhou,Jiaxing and Shaoxing of Zhejiang province were divided into two groups: 430 GPs from 10 community health centers received training for hypertension management using “ expert-guided networking tracking system” (intervention group) in December 2008 and 425 GPs from another 10 health centers received conventional training (control group).Questionnaire surveys about the knowledge and skill of hypertension management were conducted before and 3 y after training.Results The awareness rates of knowledge about hypertension prevention and control,non-drug therapy and drug therapy increased from 37.0％ (159/430),45.6％ (196/430),42.8％ (184/430) to 66.8％ (284/425),81.4％ (346/425),77.6％ (330/425),respectively and the accuracy of case analysis increased from 38.4％ (490/1290) to 73.3％ (946/1290) (P ＜0.01) after training in intervention group.Meanwhile the knowledge and case management abilities in control group were also improved after conventional training,but the degree was significantly lower than that in the intervention group.Conclusions “Expert-guided networking tracking system” can significantly improve the knowledge and skills for hypertension management in community general practitioners.

Key words: 
Hypertension;  Community health services;  Questionnaires;  Training
How does it work?——Oscillatory Blood Pressure Monitoring Devices
Authors: Abi Berger
Journal: BMJ (2001)

Pressure against using mercury in clinical practice is coming from environmentalists, and, in line with other countries in Europe, mercury column devices for measuring blood pressure are likely to be stopped being manufactured soon in Britain.

Aneroid (or clock face) devices which also depend on auscultation are gaining popularity, as are devices which depend on oscillation. Oscillatory devices produce a digital readout and work on the principle that blood flowing through an artery between systolic and diastolic pressures causes vibrations in the arterial wall which can be detected and transduced into electrical signals.

With an oscillatory device, a cuff is inflated over the upper arm or wrist. The new models use “fuzzy logic” to decide how much the cuff should be inflated to reach a pressure about 20 mm Hg above systolic pressure for any individual. When the cuff is fully inflated to this pressure, no blood flow occurs through the artery. As the cuff is deflated below the systolic pressure, the reducing pressure exerted on the artery allows blood to flow through it and sets up a detectable vibration in the arterial wall. When the cuff pressure falls below the patient's diastolic pressure, blood flows smoothly through the artery in the usual pulses, without any vibration being set up in the wall. Vibrations occur at any point where the cuff pressure is sufficiently high that the blood has to push the arterial wall open in order to flow through the artery.

The vibrations are transferred from the arterial wall, through the air inside the cuff, into a transducer in the monitor that converts the measurements into electrical signals.


These digital devices deflate at about 4 mm Hg per second, making them sometimes seem slower to use than auscultatory aneroid devices, but they are more accurate. 






Arrhythmias introduce additional vibrations within the arterial wall, presenting problems for detecting blood pressure regardless of the technique employed. Elderly people have less elastic arteries, but even the weakest vibrations are detectable using oscillometric devices and the correct sized cuff. Bladders within upper arm cuffs must encircle 80% of the arm's circumference.