tbuckley/cabot-search huggingface dataset:
Phase II trial of clinical activity and safety of ceritinib combined with stereotactic ablative radiotherapy (SABR) in lung adenocarcinoma patients.
Authors: Saad A. Khan, David E. Gerber, Hong Zhu, Randall S. Hughes, Samantha Mannala, Sawsan Rashdan, Jonathan Dowell, Kenneth D. Westover, Jessica Saltarski, Kasia Harrah, Laurin Priddy, Hak Choy, Robert D. Timmerman, Rolf A. Brekken, Noah Sorrelle, Puneeth Iyengar
Journal: Journal of Clinical Oncology (2020)

e21571 Background: ALK -targeting drugs and SABR are combined in patients with metastatic cancer, anecdotally yielding clinical benefit. However, the precise impact of the combination and the optimal time to introduce SABR remain unknown. Methods: This completed phase 2 study (NCT02513667) had a primary objective of doubling progression free survival (PFS) for ALK+ lung adenocarcinoma patients by consolidating all remaining disease with SABR, 8-10 weeks after ceritinib initiation. Patients who then progressed could receive repeat SABR as long as they then resumed ceritinib. Patients were divided into ALK-inhibitor naïve vs previously treated cohorts. Oligometastatic disease was NOT a requirement for study entry, CNS disease was permitted. Blood was serially analyzed for variation in 1. blood cfDNA detection of resistance mechanisms 2. flow cytometric analysis of white cell populations. Results: 14 patients were enrolled out of a planned 33; 7 female; 3 hispanic/latino; median age was 53 years (range 31-78); 5 patients had previously received crizotinib. 4 patients stopped ceritinib within 30 days due to toxicity, despite dose reductions or with-food administration. However, all patients still completed initial SABR consistent with protocol time-points. Patients predominantly had thoracic disease irradiated (11/14, 78%). Two patients had only brain metastases treated and 1 had bone only metastases treated. 4 had one fraction SBRT regimens (16-24 Gy per fraction) delivered to disease, 3 had three fraction SBRT regimens (9-11 Gy per fraction) delivered to disease, and 7 had five fraction SBRT or 15 fraction hypofractionated regimens (6 Gy per fraction or 3Gy per fraction, respectively) delivered to disease. Disease control in all irradiated areas was 100%. There was no significant grade 3 or higher toxicity associated with radiation. Broad variability in baseline and serial levels of circulating PMN-MDSC, VEGFR2, FoxP3+, CD56+CD16+ and various T-cell populations showed no clinical correlation. The trial terminated early due to increased use of alternative targeted therapies, thus the primary endpoint was not met. 8 patients had CR/PR/SD as best response. Including those who did not tolerate ceritinib, median PFS was 12 months, max of 31 months with 1 ongoing response. Conclusions: Consolidative SABR after ALK therapy is well tolerated, can be repeated and may prolong PFS compared to drug alone. Ceritinib toxicity meant higher rates of discontinuation but this did not prevent consolidative SABR in any patient. Clinical trial information: NCT02513667.
The clinical significance of gabapentin in combination with opioids in controlling outbreak of pain in cancer patients.
Authors: Xue Zhang, Da Jiang, Qingyu Yan, Fang Huang, Hui Jin, Shaoshuang Fan, Ying Li, Xinliang Zhou, Zhe Wang
Journal: Journal of Clinical Oncology (2020)

e24142 Background: This study compared the pain relief effects of opioids combined with gabapentin and opioids alone after an outbreak of pain in patients with opioid-tolerant cancer pain to explore better cancer pain management. Methods: A total of 60 patients with moderate and severe cancer pain from September 2016 to April 2017 in the Department of Oncology of the Fourth Hospital of Hebei Medical University. They were randomly divided into two groups when they experienced an outbreak of pain, only oxycodone hydrochloride sustained-release tablets group (A group) 30 cases and gabapentin capsule combined with oxycodone hydrochloride sustained-release tablets group (B group) 30 cases, The degree of pain relief before and after treatment, the consumption of oxycodone hydrochloride sustained-release tablets, quality of life scores and adverse reactions, and nighttime sleep time were compared between the two groups. Results: 1. The NRS score in group B after treatment was significantly lower than that in group A after treatment (1.83±0.46 vs. 2.30±0.75). There was a statistically significant difference (P &lt; 0.05). 2. The consumption of oxycodone hydrochloride sustained-release tablet in group B was lower than that in group A (19.000±6.074 vs. 25.667±10.063). There was statistical significance (P = 0.003). 3. The quality score was higher than before, and the quality of life score in group B was higher than that in group A (P &lt; 0.05). 4. The main adverse reactions in both groups were constipation, nausea, vomiting and dizziness. The incidence was 86.67% vs. 50.00%、33.33% vs. 23.33%, 20.00% vs. 16.67%, respectively, there was no significant difference (P &gt; 0.05). The nighttime sleep time of both groups was higher than that before treatment (6.017±0.636 vs. 5.167±0.735, 6.433±0.583 vs. 5.167±0.661). 5. The nighttime sleep time of Group B was longer than that of Group A after treatment (6.433±0.583 vs. 6.017±0.636). The difference was statistically significant (P &lt; 0.05). Conclusions: Opioids combined with gabapentin are superior to opioids alone in the treatment of cancer pain with analgesic efficacy, improved quality of life, reduced opioid consumption, adverse drug reactions, and effective night time sleep.
Molecular subtyping reveals stage-specific mutational landscape and prognostic predicting factors of stage IV NSCLC.
Authors: Yuqing Huang, Yingshun Yang, Jianfei Yao, Qiang Liu, Bingzhi Wang, Xianjun Min, Guotian Pei, Shuai Wang, Xiaoyu Wang, Jun Liu, Shiying Dang, Tanxiao Huang, Mingyan Xu, Lele Song
Journal: Journal of Clinical Oncology (2020)

e21607 Background: The mutational profile of non-small cell lung cancer (NSCLC) has been widely studied. However, the correlation between mutational profile and the prognosis of various molecular subtypes of NSCLC has not been fully investigated. Methods: We established the mutational landscape from 244 stage I-IV NSCLC patients using a 605-gene next generation sequencing panel. Molecular subtyping was performance based on the mutational status of EGFR, TP53, KRAS and STK11 genes according to reported methods. Sequencing data were analyzed with R packages and statistics analysis was performed with Graphpad PRISM 5.0 software. P ≤ 0.05 was regarded as statistically significant. Results: Differential SNV/INDEL mutation frequency across stage I-IV was found in EGFR, TP53, ATM, CDKN2A and NF1 (P &lt; 0.05), differential CNV frequency was found in EGFR, RB1, PIK3CA, TERT, KRAS, FGFR1 and ERBB2 (P &lt; 0.05), and differential SV frequency was found in ROS1 (P &lt; 0.05). TMB of stage III-IV patients was higher than those of stage I (P &lt; 0.05). TMB was higher in patients with TP53 but without EGFR mutations (P &lt; 0.05). The association between prognosis and mutational status was further investigated in stage IV NSCLC. Patients with EGFR SNV/INDEL mutations exhibited better PFS and OS time, while patients with KRAS and/or STK11 SNV/INDEL mutations, or without mutations in EGFR, TP53, KRAS and STK11 exhibited worse PFS and OS time. However, no significant difference was observed in PFS and OS between patients with or without TP53 SNV/INDEL, EGFR CNV, ERBB2 CNV or TERT CNV variations. Further analysis showed that male or age≥62 exhibited worse OS time (P &lt; 0.05), while smoking history, palliative surgery and palliative radiotherapy did not affect the PFS and OS time of stage IV patients. Conclusions: We found differential frequency in SNV/INDEL, CNV and SV variations across stage I-IV NSCLC. EGFR SNV/INDEL, KRAS SNV/INDEL, STK11 SNV/INDEL mutation, gender and age were found to be prognostic predicting factors for stage IV NSCLC.
Liver biopsy and clinical characteristics of inactive HBsAg carriers
Authors: Liangang Mao, Airong Hu, Suwen Jiang, Huadong Yan
Journal: BMJ (2016)

Objective
To assess the liver biopsy and the clinical characteristics of inactive HBsAg carriers.


Methods
One hundred and ten inactive HBsAg carriers, including 76 males and 34 females aged (38.9±9.4) years (21-66), underwent liver biopsy from January 2011 to September 2015, the histopathological findings and clinical features were analyzed.Among 110 cases the inflammation activity (A) was <A2 in 73 cases and ≥A2 in 37 cases; the fibrosis (F) <F2 in 63 cases and ≥F2 in 47 cases.The upper limits of normal (ULN) for ALT was defined as 30 U/L for men and 19 U/L for women according to World Health Organization (WHO) standard, and 50 U/L for men and 40 U/L for women according to Chinese national standard.There were 59 cases with ALT <1×ULN of WHO standard and 110 cases with ALT <1×ULN of Chinese standard.


Results
In 110 inactive HBsAg carriers, there were 100 cases (90.9%) ≥A1 and 37 cases (33.6%) ≥A2, 84 cases (76.3%) ≥F1 and 47 cases (42.7%) ≥F2. The severity of A and F were both higher in males than that in females, especially that of F (U=2.162, P=0.032; χ2=5.315, P=0.021). But there were no statistical differences between WHO standard group and Chinese standard group (U=0.951, 0.435; P=0.341, 0.663). Along with the increase of age, the degrees of A and F aggravated (F=3.705, 5.915; P=0.014, 0.001). The average ages in ≥A2 group and ≥F2 group were (41.7±9.6) years and (38.7±8.1) years, respectively.The independent risk factors for severity of A and F were age, gender (male) and age, respectively.


Conclusion
There may be histological damages of varying degree in liver tissues of most inactive HBsAg carriers, and for those aged 40 years and over, especially males screening of liver histological activity and fibrosis would be necessary.


Key words: 
Hepatitis B virus; Inactive HBsAg carrier; Pathology; Liver; Biopsy, needle
Attitude toward death and hospice care among medical staff and its influencing factors
Authors: Dandan Xu, Xian Jin
Journal: BMJ (2017)

Objective
The attitude towards death and hospice care was surveyed among 170 medical staff in geriatrics department and ICU of Renji Hospital and Tangqiao Community Health Service Center with the Revised Attitude towards Death Scale (in Chinese) and a self-designed questionnaire, and 158 valid questionnaires were received. The average score of negative attitude to death was 37.0±8.4 and the influencing factor was positions (P=0.02). The average score of positive attitude to death was 28.8±4.3, and the influencing factors were positions(P=0.01)and religious belief (P=0.02). The mean score of attitude toward hospice care was 35.4±3.9 and the marital status(P=0.00)was the independent factor. It is necessary for medical staff to participate in professional training for death education, which would make them to take better care for terminal stage patients with rationality and sensibility.


Key words: 
Hospice care; Attitude to death; Attitude of health personnel
Covid-19: Deadline for roll out of UK’s tracing app will be missed
Authors: Stephen Armstrong
Journal: BMJ (2020)

<h3>Background</h3> Olaparib and Niraparib are oral antineoplastics used for the maintenance treatment of high-grade ovarian cancer, relapsed, complete or partial response to platinum-based chemotherapy. Olaparib is indicated for patients with BRCA +mutation and marketed in our country: Niraparib is independent of the mutation and it is used in compassionate use. <h3>Purpose</h3> Comparing the safety profile of Niraparib and Olaparib, in the everyday clinical practice of a tertiary hospital. <h3>Material and methods</h3> Descriptive, transversal, retrospective research of all patients treated with Niraparib or Olaparib until September 2018. Data: clinical and pharmacological history (Farmatools). Variables: age, date of beginning, end and/or reintroduction of treatment, reason for suspension, initial dose, dose reduction, current dose, days of treatment and adverse effects. Analysis: SPSS Statistics. <h3>Results</h3> Eight patients with Olaparib and 11 with Niraparib, with an average age of 65 (50–86) and 61 (48–73) respectively. The median of treatment with Olaparib was 455 (25–1264) and with Niraparib 35 (2–91). Olaparib: seven (87.5%) patients started with 400 mg and one (12.5%) with 200 mg. Three (50%) needed dose reduction and all had started with 400 mg. In two patients the treatment was suspended due to death and progression respectively. Six (75%) continued in treatment (three with 400 mg, two 200 mg and one 100 mg). In one (16.7%) of them the treatment was temporarily suspended due to decreased haemoglobin and three (37.5%) had adverse effects (nausea, vomiting, stomach pain) without interruption of treatment. Niraparib: four (36.4%) patients started with 300 mg and seven (63.6%) 200 mg. Five (45.5%) patients needed dose reduction, two with initial dose 300 mg and three 200 mg: three of them continued (one of 300 mg and two of 200 mg initial dose). In five (45.5%) patients, treatment was discontinued, two (40%) due to adverse effects (neutropaenia, thrombocytopaenia and increased creatinine respectively) and three due to progression (60%), in addition temporarily suspending it due to neutropaenia. Six continued (three with 200 mg and three with 100 mg) and three of them had to temporarily interrupt it due to thrombocytopaenia. <h3>Conclusion</h3> In both treatments, the haematological adverse effects are more severe, frequent and worse tolerated in the case of Niraparib than Olaparib. In addition, greater discontinuity of treatment is observed in patients with Niraparib. <h3>References and/or acknowledgements</h3> No conflict of interest.
宫内生长受限对患儿远期神经行为及心理发育的影响
Authors: 王晓凤, 刘敬
Journal: BMJ (2012)

胎儿宫内生长受限( IUGR)是临床常见并发症之一,不但可导致胎儿体格与神经系统发育障碍,还对患儿的心理发育和神经行为等造成长期不良影响,如脑瘫发生率高、学习与记忆能力降低、认知障碍和心理行为异常等.综述近年来有关IUGR对患儿远期神经行为及心理发育的不良影响,以加强对IUGR的认识。
Acquisition of parasternal left ventricular long axis view and image interpretation
Authors: Wenying Jin
Journal: BMJ (2018)

超声心动图的切面千变万化，每个超声医师掌握的可能不尽相同，但几个标准切面是所有超声医师及心血管医师所必须掌握的。胸骨旁左心室长轴切面是首先应该掌握的第一个基本切面，除右心房、腔静脉和肺动脉，约70%的心脏结构可以通过该切面显示。该切面也是判断升主动脉、左心房、左心室的大小、功能及瓣膜功能的基本切面之一。
Manjeet Singh Riyat
Authors: Susanne M Hewitt, Mahbub M Chowdhury
Journal: BMJ (2020)

After graduating, Manjeet Singh Riyat trained in emergency medicine at Leicester Royal Infirmary and Lincoln County Hospital. Before paramedics were introduced into the NHS, he acted as team leader for the accident flying squads at both hospitals. He was also one of the first clinical research fellows in the UK and contributed to the birth of academic emergency medicine.

In 2003 Manjeet became one of four consultants in emergency medicine at the Derbyshire Royal …
Effects of practice of performance appraisal and distribution motivation system at Jimenli community health service cente
Authors: La Ta
Journal: BMJ (2013)

To evaluate the reforming effects of health service performance appraisal and distribution motivation system at our center, discuss some questions during the development and application of such an evaluation system and conduct comparative analysis of the policies and data before and after management pilot separation between revenue and expenditure. The performance evaluation system and distribution mechanism were established so as to boost the working efficiency of community health services and ensure their sustained and healthy developments.


Key words: 
Community health services; Income
小切口开胸肺活检诊断肺弥漫性病变38例
Authors: 夏军, 程邦昌, 刘先义, 王土生, 邓宏平
Journal: BMJ (2005)

回顾性分析我院38例肺弥漫性病变患者的临床资料、麻醉和手术方法,探讨采用局麻小切口开胸肺活检进行临床诊断的可行性和实用性.结果表明,37例(97.4%)获得肺组织学诊断,25例(65.8%)得以更换治疗方案.采用此方法无全麻副作用,短时纵隔反应对呼吸、循环无干扰,可取得足够的肺组织,对经过各种无创或微创检查不能明确病因的肺弥漫性病变,是一种可采用的诊断手段,但应注意选择合适病例。
Training needs of continuing medical education for gereral practitioners in urban and suburban of Shanghai
Authors: Jie Gu, Sun-fang Jiang, Xiang-jie Zhang, Yao Liu, Ming-hui Peng
Journal: BMJ (2013)

Objective
To assess the continuing medical education (CME) and training needs for gereral practitioners (GPs) in urban and suburb of Shanghai.


Methods
Gereral practitioners in urban (n=710) and suburb (n=843) of Shanghai attending two municipal training programs were interviewed with self-designed questionnaire during July 2011 to May 2012.


Results
Urban group included 710 GPs whose mean age were (36.7±6.8) y and 33.0% were male. Suburban group had 843 GPs whose mean age were (36.6±5.1) y and 33.2% were male. The survey showed that 84.6% of urban group and 85.6% of suburban group had attended CME before. There was no statistical difference in the overall satisfaction of CME between two groups (Z=-0.895,P=0.371). The propotion of satisfied and very satisfied was 45.1% and 13.8% in urban groupt, while it was 49.5% and 9.1% in suburb group. The overall satisfaction rates of enhancing basic theories (Z=-2.296, P=0.022) and skills (Z=-2.013, P=0.044) and CME textbooks (Z=-2.819, P=0.005) were higher in suburban group than those in urban group. Both of them agreed that the contents of CME were divorced from reality of practice (60.3% vs. 65.2%, χ2=3.213, P=0.082). The percentages of complain of insufficient training time (19.7% vs. 11.0%,χ2=18.045, P<0.05) and contents (7.5% vs. 4.3%, χ2=5.747, P=0.019), and weak leadership commitment (14.3% vs. 6.5%, χ2=19.95, P<0.05) were higher in suburban group than those in urban group. On the contrary, the delivery of repeated contents (24.8% vs. 34.8%, χ2=15.327, P<0.05) and long training time (16.4% vs. 28.2%, χ2=26.055, P<0.05) were lower in suburban group than those in urban group. Using case study in the teaching was the common choice of both groups (73.3% vs. 78.0%, χ2=0.635, P=0.426). Compared to urban group, suburban group was more likely to choose lecture of theory (63.6% vs. 50.8%, χ2=6.712, P=0.010) rather than problem based learning (43.1% vs. 51.9%,χ2=4.273, P=0.010).


Conclusions
Both urban and suburban GPs in Shanghai are generally satisfied with the CME programs. There are some discrepancies in training needs of CME between urban and suburben area in Shanghai, indicating that the CMB programs need to be designed according to the needs of trainees in urban or suburb areas.


Key words: 
General practioner; Education, medical, continuing; Needs assessment
Reply
Authors: Guadalupe García‐Tsao, Iaarah Montalvo‐Gordon
Journal: Hepatology (2020)

Potential conflict of interest: Nothing to report. We appreciate the interest in our report and the comments in the correspondence from Drs. Kumar and Kulkarni, who express concerns about SGLT2‐inhibitors (SGLT2‐I) being nothing more than loop diuretics, and from Dr. Patoulias et al., who express concerns about weight reduction with SGLT2‐I being more due to fat loss, with volume loss being an only transient effect. Our case reports suggest that SGLT2‐I do not have the same mechanism of action as conventional diuretics. The three cases reported had been responsive to spironolactone and furosemide, but these had to be discontinued because of the development of complications (encephalopathy, hyponatremia or acute kidney injury, respectively), which led to recurrence of volume overload. The fact that SGLT2 inhibitors alone led to resolution of volume overload (and in two cases SGLT2‐I were dosed for this purpose), without recurrence of complications, is indicative that their mechanism of action may go beyond a natriuretic effect. In fact, SGLT2 inhibitors have a natriuretic and an aquaretic effect, and their use has been associated with a significant decrease in total body water both in patients with normal renal function(1) and in patients with heart failure.(2) This latter group of patients is particularly important, because the mechanisms of fluid retention in heart failure are similar to those of cirrhosis (and not present in patients with diabetes without heart failure). In the placebo‐controlled physiological study by Griffin et al., performed in patients with diabetes and stable heart failure, SGLT2‐I led to significant natriuresis and reduction in total body water without untoward effects on blood pressure or neurohumoral activation.(2) In contrast to loop diuretics, SGLT2‐I, by increasing sodium chloride delivery to the macula densa, would counterbalance the effect of a reduction in plasma volume in increasing renin‐angiotensin‐aldosterone system activity,(2) an effect that persisted for 14 days. On the other hand, loop diuretics are associated with urinary potassium wasting, which does not occur with SGLT2‐I,(2) with hypokalemia being a well‐known precipitant of hepatic encephalopathy,(3) as occurred in one of the cases reported. Our interesting observation in only three cases should obviously not lead to the use of SGLT2‐I in the management of patients with cirrhosis and ascites, but should lead to further investigations that will clarify their mechanism (and duration) of action and, if promising, to the performance or randomized controlled trials that will determine the place of SGLT2‐I in the management of cirrhotic ascites. These studies may actually demonstrate that SGLT2‐I are in fact "magic" pills for the management of ascites in an as yet to be determined population of patients with cirrhosis (with or without diabetes).
总编寄语
Authors: 杨秉辉
Journal: BMJ (2008)

光阴荏苒,一年容易又秋风,不过这一年我们却过得不那么轻松.汶川大地震,举世震惊,全国动员抗震救灾,显示了中国人民不屈不挠的精神,赢得了世人的崇敬.奥运会成功举办,金牌总数世界第一,圆了中国人的奥运梦,令世界对中国刮目相看.总算过来了,2008年应该是中国人民胜利的一年。