tbuckley/cabot-search huggingface dataset:
Dietary consumption of tea and the risk of prostate cancer in the prostate, lung, colorectal, and ovarian cancer screening trial.
Authors: Robert J. Thomas, Alex McConnachie, Bethany Stanley, Madeleine Williams
Journal: Journal of Clinical Oncology (2020)

e13559 Background: The popular beverage tea, brewed from infused leaves of camellia sinesis, contains non-phytoestrogenic polyphenols such as flavonoids, anthocyanidins, flavanols (epigallocatechin gallate); phenolic acids (ellagic acid) and stimulants (caffeine, theophylline). Laboratory studies report tea promotes antioxidant enzyme formation, slows cancer cell proliferation and unblocks apoptosis. Clinically, the Pomi-T randomised study reported tea extract (along with three other foods) reduced PSA progression in men with prostate cancer 1 . Evidence of prostate cancer prevention, however, from prospective cohort data is conflicting with one recent study even implying an increased risk 2 . Methods: We analysed 25,097 men within the intervention arm of the 155,000 participant PLCO screening trial. Histological confirmed cases of prostate cancer were reported in 3,088 men (12.3%) during the 11.5 year follow up. Tea consumption was assessed with a food frequency questionnaire (FFQ). Baseline characteristics were compared between groups using Chi-square and Kruskal-Wallis tests. Cox regression models were used to assess the association between tea intake and prostate cancer incidence. Results: Overall tea consumption was associated with a significantly lower risk of prostate cancer (p = 0.009). More precisely, the participants in the highest third of consumption group had a significantly lower risk compared to those in the lowest third (HR 1.16 (CI 1.05-1.29, p = 0.004). This pattern persisted with adjustments for age, sex, race and education level (p = 0.034), family history of cancer (p = 0.037). Those who never drank tea, however, had no statistical lower risk of prostate cancer compared to other groups (p = 0.501). Conclusions: Among tea drinkers, this data revealed a positive association between drinking tea and a reduced risk of prostate cancer. This data supports the consideration of future prospective intervention studies investigating the role of tea as part of a prostate cancer prevention programme. 1. Thomas et al. The NCRN Pomi-T RCT. Prostate cancer &amp; prostatic diseases (2014), 2,180. 2. Reger et al. Dietary isoflavones and prostate cancer risk. Int J. Cancer (2017), 142; 4, 719.
Monitoring and analysis of perinatal defects in Lishui city in last decade
Authors: Yali Zhang, Juhong Lan, Zhuochao Lyu, Lihua Xiao
Journal: BMJ (2016)

Objective
To analyze the dynamic changes of perinatal defects in Lishui city from 2005 to 2014.


Methods
According to hospital-based data, 87 294 fetuses and infants aged from 28 weeks of gestation to 7 days after birth were monitored for birth defects in Lishui city from 2005 to 2014.


Results
Among 87 294 perinatal infants, birth defects were found in 1 914 cases with a incidence of birth defects of 219.3/ten thousand, which was on the rise year by year except 2009. The incidence of birth defects was 235.1/ten thousand (737/31 352) in urban areas, which was significantly higher than that in rural areas (210.4/ten thousand, 1 177/55 942) (χ2=5.705, P 0.05). Among 1 914 cases of defects, 657 were detected prenatally and 1 257 case were detected within 7 days after birth. Congenital heart disease was the most common birth defect, followed by polydactyly, cleft lip, microtia and syndactyly. Birth defect accounted for 32.74% (278/849) of all perinatal deaths and the ratio was on the rise since 2010.


Conclusion
There is an upward trend in incidence of birth defects in Lishui city in the last decade; the incidence of birth defects in urban areas is significantly higher than that in rural areas; the incidence of congenital heart disease is high, and birth defects are the main cause of perinatal death.


Key words: 
Congenital abnormalities; Perinatal period; Incidence; Cross-sectional studies
Report of 5 cases of pediatric plastic bronchitis and review of related literature
Authors: Chun-mei Zhu, Ling Cao, Li Chang, Qi Zhang, Fei Wang
Journal: BMJ (2013)

To report the clinical course of 5 cases of pediatric plastic bronchitis and review the related literature. A total of 113 cases of pediatric plastic bronchitis occurring in China from 2000 to 2012 were retrieved through the databases of CNKI and Wanfang Med Online. Retrospective analyses were performed for the main symptoms, courses, etiologies, imaging findings, histopathological classifications, therapies and prognosis of 118 cases. Pediatric plastic bronchitis was one of critical diseases. Most of them had a rapid onset and a mortality rate. Bronchoscopy examination was essential for definite diagnosis and effective treatment. Airway management and chest physiotherapy were primary adjuvant tools. Early diagnosis and bronchoscopic treatment might result in improved prognosis.


Key words: 
Airway obstruction; Plastic bronchitis
Early diagnosis and treatment of chronic obstructive pulmonary disease
Authors: Jinping Zheng
Journal: BMJ (2018)

慢性阻塞性肺疾病(慢阻肺)的患病率显著增高，其中超过九成是严重程度较轻的患者，但慢阻肺的早期诊断和早期治疗却一直没有受到足够的关注。目前存在的几个误区包括混淆疾病早期与轻度的概念，肺功能检查率较低致早期诊断不足，治疗观念落后使无症状早期患者缺乏治疗等。文章通过介绍早期慢阻肺的特点及类型，并倡导关注慢阻肺的早期发现，积极普及肺功能检查，熟悉慢阻肺的早期特点与临床表现，重视对早期(包括无症状)患者的治疗。
LP-300 as a potential first-in-class combination agent with tyrosine kinase inhibitors (TKIs) in non-smoker lung adenocarcinoma.
Authors: Aditya Kulkarni, Aulma Parker, Kamwing Jair, Pavankumar Petluru, Xinghai Chen, Harry Kochat, Frederick H. Hausheer, Umesh Kathad, Kishor Bhatia, Kerry Barnhart, Panna Sharma
Journal: Journal of Clinical Oncology (2020)

e21660 Background: Lung cancer in non-smokers (LCINS) is the seventh leading cause of death among solid tumors. LCINS is more frequent in women, and the histological incidence of adenocarcinoma is higher among non-smokers. The mutation pattern by smoking status in non-small cell lung cancer (NSCLC) is distinct with genomic alterations in EGFR, MET and ROS1 being more frequent in non-smokers. Non-smoking status is the strongest clinical predictor of benefit from the EGFR TKIs. Lantern Pharma is developing LP-300/Dimesna, a non-toxic, well-tolerated, water-soluble disulfide as a combination therapy agent potentially indicated in female never-smokers with adenocarcinoma. Retrospective subgroup analyses of prior phase 3 trial data showed substantial overall survival benefit for LP-300 in combination with standard chemotherapy in patients with advanced NSCLC, especially in the female non-smoker adenocarcinoma subgroup (13.4 months in control arm to 27 months in treatment arm). Purpose of this work conducted at BioNumerik Pharmaceuticals was to determine if LP-300 modulates activity of selected receptor tyrosine kinases relevant to non-smoker NSCLC. Methods: In vitro luminescence-based kinase assays were used to evaluate the effect of LP-300 and LP-300-derived mesna-disulfide heteroconjugates, Erlotinib, and Crizotinib, in combination and as single agents, on EGFR, MET, and ROS1 kinase activity. Results: LP-300 inhibited WT EGFR kinase and MET kinase. LP-300 had a time-dependent inhibitory effect on ROS1 kinase activity. LP-300 and LP-300-derived mesna-disulfide heteroconjugates stimulated Erlotinib-mediated inhibition of WT and T790M EGFR. T790M EGFR is normally insensitive to Erlotinib but when LP-300 was used with Erlotinib, inhibition was more prominent. LP-300 also stimulated Crizotinib-mediated inhibition of MET kinase and displayed time-dependent stimulation of Crizotinib-mediated inhibition of ROS1 kinase. Conclusions: LP-300 is a multi-targeted modulator of enzymatic activities of EGFR, MET and ROS1, and potentiates the activity of Erlotinib and Crizotinib. EGFR family members contain conserved extracellular structures that are stabilized by disulfide bonds. Compounds that disrupt extracellular disulfide bonds could inactivate EGFR and potentially downregulate EGFR-dependent proliferative signaling in cancer cells. We propose LP-300 as a Disulfide Bond Disrupting Agent (DDA) that may complement existing EGFR-targeted agents functioning through alternate mechanisms.
并发消化道出血区域性脾静脉高压症行手助腹腔镜诊治的体会
Authors: 葛恒发, 姜宝飞, 于仁
Journal: BMJ (2011)

区域性脾静脉高压症是由于各种原因如胰腺炎、胰腺假性囊肿、外伤、肿瘤等引起脾静脉回流受阻所致.临床少见并容易被忽视,常并发上消化道出血.随着影像学技术的发展,其确诊率明显提高.现将本院2005年1月至2010年1月收治的11例区域性脾静脉高压症并发消化道出血患者,应用手助腹腔镜行脾切除加贲门周围血管离断术治疗的临床资料报告如下。
Comparison of professional cognition between trainees of GP assistant training program and GP training program in Shanghai
Authors: Jie Gu, Xuan Lu, Ying-min Chen, Zhi-gang Pan, Kun Zhu, Xiu-ling Ying, Yue-lin Xie, Yao Shen, Jing Yuan, Yu-ting Jiang
Journal: BMJ (2013)

Objective
To investigate and compare  professional cognition between trainees of general practitioner (GP) assistant training program (3+2 mode) and GP training program (5+3 mode) in Shanghai.


Methods
A questionnaire survey on professional cognition was conducted among 30 trainees [(22.6±0.7) y, 16.7% male] of 3+2 program from Jiading District and 76 trainees [(24.6±1.8) y, 35.5% male] of 5+3 program from 6 GP training bases in Shanghai during August to October 2012.


Results
The overall assessment of 3+2 trainees was higher than that of 5+3 trainees in three aspects: the social status of  (mean rank 69.37 vs. 47.24, Z=-3.589, P<0.001), the career prospects of  (mean rank 66.13 vs. 48.51, Z=-2.953, P=0.003) and the social demand for  (mean rank 68.17 vs. 47.71, Z=-3.261, P=0.001). 93.4% (28/30) of 3+2 trainees and 47.4% (36/76) 5+3 trainees considered that what was most needed for any improvement of GPs was raising income. The expected income of 5+3 trainees was higher than that of 3+2 trainees [(8436±2963) vs. (6600±2694) yuan/m, t=-3.087, P=0.003]. About employment intention, only 35.5% (27/76) of 5+3 trainees regarded community health service centers as first choice, while 39.5% (30/76) of them preferred secondary or tertiary hospitals. Logistic regression showed that  preferred employment intention of 5+3 trainees was not related to their gender, household registry, school of graduation, educational background, study major, working experience and expected income.


Conclusions
The survey indicates that  professional cognition of 5+3 trainees need to be improved, their employment intention need to be adjusted and their income need to be raised.


Key words: 
Physician assistants; General practioner; Career choice; Questionnaires
Toxicity and tolerability of DA-EPOCH-R for aggressive lymphomas in the elderly: A retrospective cohort study.
Authors: Shanley Banaag, Manish Singla, Mary Kwok, Dechang Chen
Journal: Journal of Clinical Oncology (2020)

e20030 Background: There remain concerns regarding appropriate patient selection for dose-adjusted EPOCH-R in the treatment of lymphoma, particularly diffuse large B-cell lymphoma, where efficacy is comparable to R-CHOP but significantly more toxic. As the average age at diagnosis of DLBCL is between 60-70 years old, ability of elderly patients to complete and tolerate therapy is critical in treatment decision. Our aim was to investigate the differences in tolerability and toxicity of DA-EPOCH-R among different age groups. Methods: We conducted a retrospective review of patients treated with DA-EPOCH-R at Walter Reed National Military Medical Center. The institutional pharmacy database was queried to identify adult patients diagnosed with lymphoma and treated with DA-EPOCH-R from July 2005 through March 2018. Chart reviews were performed and information on dose reductions, delays, and adverse treatment effects were recorded and stratified between patients aged &lt; 45 years, 45-59, 60-74 and ≥75 years. Results: 70 patients were identified for review. Average age was 55.8 +/- 15.5 years; 49% of patients were ≥ 60 years, including 9 patients who were ≥ 75 years. Diagnoses included diffuse large B-cell lymphoma (n = 46), transformed lymphoma (n = 12), primary mediastinal B-cell lymphoma (n = 4), Burkitt lymphoma (n = 3), T-cell lymphoma (n = 3), and high-grade B-cell lymphoma, NOS (n = 2). There was no significant difference in the median number of cycles completed between the age groups ( p= 0.2540). However, there was a significant difference in the maximum dose level achieved ( p= 0.0003). The median dose level achieved was 3.4 for patients age &lt; 45 (range 1-5), 2.5 for patients age 45-59 (range 1-5), 1.88 for patients age 60-74 (range 1-4), and 0.88 for patients age ≥75 (range -2 to 2). Patients greater than 60 years were more likely to have any dose delay ( p= 0.001), more total dose delays (p = 0.004), and to experience gastrointestinal (GI) toxicities ( p= 0.014). There were no significant differences seen in peripheral neuropathies ( p= 0.425) nor hospitalizations ( p= 0.242). One patient passed away due to toxicity. Conclusions: This study demonstrates the use of DA-EPOCH-R in a real-world setting for the treatment of aggressive lymphomas. Our data suggest that elderly patients can complete all planned courses of DA-EPOCH-R but do not reach the dose intensity achieved by younger patients. In addition, elderly patients are more likely to require dose delays and experience GI toxicities without significant differences in hospitalizations or peripheral neuropathy.
Correlation between 24-hour proteinuria and spot urine albumin to creatinine ratio in systemic light chain amyloidosis.
Authors: Alissa Visram, Abdullah S. Al Saleh, Eli Muchtar, Jennifer McDonald, Harsh V Parmar, Iuliana Vaxman, Angela Dispenzieri, Francis Buadi, Morie A. Gertz, Nelson Leung
Journal: Journal of Clinical Oncology (2020)

8549 Background: Proteinuria evaluation is essential for diagnosing and monitoring of renal involvement in light chain (AL) amyloidosis. A 24 hour protein collection (24h UP) is the gold standard for proteinuria assessment however it is cumbersome and can be inaccurate. A spot urine albumin to creatinine ratio (uACR) has been proposed as a convenient method to estimate 24hUP. We aimed to validate the correlation between uACR and 24hUP in a large cohort of patients. Methods: We retrospectively studied systemic AL amyloidosis patients evaluated between 2010 and 2019 at Mayo Clinic, with a uACR and 24hUP collected less than 7 days apart. Linear regression analysis was used to construct a prediction model for 24hUP with uACR as the primary predictor. Possible confounders (age, gender, body mass index, morning versus afternoon spot urine collection, estimated glomerular filtration rate) for the primary relationship between uACR and 24h UP were evaluated in the model. We used receiver operating characteristic (ROC) analysis to identify the best uACR cutoff to predict significant proteinuria (defined as a 24hUP &gt; 500mg). Results: We included 665 patients, with a median age of 66 years (IQR 59-72). The spot urine was collected in the morning (before 1200 hours) in 382 (57%) patients, and in the afternoon in 283 (43%) patients. The median 24hUP was 321 (IQR 129-2512.5) mg, median uACR was 107 (IQR 13.5-1845) mg/g, and median serum creatinine was 1.2 (IQR 1-1.8) mg/dL. The uACR correlated well with 24h UP (Pearson’s r= 0.83, 95% CI 0.80-0.85). Linear regression showed that E (24h UP i ) = 362 + 1.05(uACR i ), and this model was statistically and clinically significant (p &lt; 0.001 and R 2 of 0.68, respectively). Age, gender, body mass index, eGFR, and time of day of spot urine collection did not confound the primary relationship between uACR and 24hUP, and no collinearity was observed. A uACR cutoff of &gt; 280 mg/g was the best predictor of a 24hUP &gt; 500 mg (area under the ROC curve 0.98, sensitivity 92%, specificity 97%). For simplicity, we assessed the predictive value of uACR &gt; 300 mg/g for 24h UP &gt; 500 mg. Among patients with 24huACR &gt; 300 mg/g 264 (96%) had a 24hUP &gt; 500 mg, and 31 (7%) of patients with uACR &lt; 300 mg/g had a 24h UP &gt; 500 mg (p &lt; 0.001). Conclusions: In systemic AL amyloid patients, we showed that uACR on a random urine sample correlated well with 24h UP, and can be used to estimate proteinuria with a linear regression model. Based on these findings, and the convenience of uACR testing for patients, we propose that uACR should be used to monitor renal response to AL amyloidosis therapy.
MiST1: A phase IIa trial of rucaparib in patients harbouring BAP1/BRCA1 deficient relapsed malignant mesothelioma.
Authors: Dean Anthony Fennell, Liz Darlison, Peter Wells-Jordan, Catherine Jane Richards, Aarti Gaba, Charlotte Poile, Caroline Cowley, Alan G Dawson, Molly Scotland, Vina Bhundia, Bruno Morgan, Sarah Anthony, Adrian Nicholson, Cassandra Brookes, Seid Mohammed, Amy Branson, Amy King, Anne L. Thomas
Journal: Journal of Clinical Oncology (2020)

9057 Background: Malignant Mesothelioma (MM) remains an incurable cancer lacking effective treatments in the relapsed setting. Personalised therapy is still in its infancy. Homologous recombination (HR) deficiency associated with BRCA1 mutation has been shown to predict sensitivity to inhibition of poly-ADP ribose. In MM, BRCA1 associated protein 1 carboxy-terminal hydrolase (BAP1) is frequently mutated. It regulates both HR, and BRCA1 expression which is lost in 38% of mesotheliomas. Mesothelioma Stratified Therapy 1 (MiST1) was designed to test the hypothesis that BAP1/BRCA1 negative mesotheliomas would exhibit defective HR and exhibit sensitivity to PARP inhibition. Methods: MiST1 was a single centre, open label single arm phase IIa design with prospective molecular stratification; cytoplasmic/negative BAP1 or BRCA1 deficient MM was deemed eligible. Treatment was 600mg BD rucaparib (R) PO daily every 28 days for 6 cycles or until disease progression, unacceptable toxicity, withdrawal or death. Primary outcome was disease control rate at 12 weeks (DCR12w); secondary outcomes safety and toxicity profile, objective response rate (ORR) and DCR at 24 weeks (DCR24w). The null hypothesis states the true DCR12w is less than or equal to 25% and was tested against a one-sided alternative hypothesis that the DCR12w will be equal to or greater than 50%. Results: Between February 2019 and June 2019, 26 patients (pts) were eligible and consented to MiST1, median age 65.5 years, 85% are male and 15% female. Of these pts 15% had an ECOG performance status (PS) of 0 and 85% had an ECOG PS of 1. Molecular eligibility was 89% for BAP1 alone, 50% BRCA1 alone, and 39% BAP1+BRCA1. Primary tumour site was thoracic (96%) and subtype epithelioid (81%). DCR12w was 57.7% (95% CI, 36.9 - 76.7), DCR24w was 23.1% (95% CI, 9.0 – 43.7) and ORR was 11.5% (95%CI, 2.5 – 30.2). R was well tolerated with 9% (15/166) grade (G) 3/4 toxicities seen in 10 pts (38%), with no G5 toxicities. The most common adverse events were nausea occurring in 18 pts (69%), fatigue in 14 pts (54%), and decreased appetite in 10 pts (38%). Six cycles of R was received by 8 pts (30.8%). Dose reductions occurred in 9 pts (n = 8; 1 dose and n = 1; 2 doses). Dose delays occurred in 14 pts. Conclusions: MiST1 using the PARP inhibitor R met its primary endpoint of disease control rate at 12 weeks, showing promising efficacy with manageable toxicity. HR deficiency mutation signature enrichment is being investigated to refine the identification of responders to PARP inhibition. PARP inhibition warrants further investigation in MM. Clinical trial information: NCT03654833.
Health risk factor and effectiveness of intervention for hospital employees
Authors: 邓晓倩, 黄建始, 刘斌, 江坤尧
Journal: BMJ (2010)

Objective To evaluate the effectiveness of intervention for health risk factor in hospital employees. Methods This study was carried out among 339 employees of a hospital in Jinan, Shandong Province. Based on the results of Health Risk Appraisal for 14 health risk factors, we designed a 6-months intervention program for the most widely distributed and intervenable health risk factors; and then evaluated the changes of health risk factors after 6 months. Results After 6-month intervention the prevalence of 3 health risk factors decreased (P ＜ 0.05 ): physical inactivity decreased from 57.8% to 38.6%,hyperlipidemia from 9.4% to 5.3%, and unhealthy dietary from 28.9% to 14.8%. Compared with the baseline data, the average number of health risk factors were reduced from 3.10 to 2. 71 ( P ＜ 0. 01 ).Conclusion The intervention can reduce health risk factors effectively.

Key words: 
Health status indicators ;  Risk factors ;  Population intervention strategy ;
Effects of pregnancy on long-term outcomes of pulmonary arterial hypertension associated with congenital heart disease: a preliminary study
Authors: Qitian Ou, Jiakai Lu, Dong Yang, Qing Ye, Jie Gao, Limin Geng, Jianping Sun, Tengke Wang, Jinglan Zhang
Journal: BMJ (2018)

Objective
To investigate the effects of pregnancy on long-term outcomes of pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD).


Methods
Women with PAH-CHD who had undergone pregnancy under the care of Beijing Anzhen Hospital from 2004 to 2013 were retrospectively identified and 1∶1 matched to nulliparous PAH-CHD females (controls). Functional status and other clinical data were recorded for each group at baseline and follow-up.


Results
We successfully matched 40 pairs of pregnant and non-pregnant women with PAH-CHD. The patients were followed up for a mean of (6.5 ± 1.9) years, the outcomes of patients were documented during April 2016 to October 2016. No deaths occurred in either group during the study period. There were no statistically significant differences in long-term cardiac function between the two groups (Z=-1.41, P=0.16). After adjusting age, timing of follow-up, specific drug therapy and Eisenmenger′s syndrome, pregnancy didn′t have significant effect on the long-term deterioration of cardiac function in PAH-CHD patients (OR=1.32, 95%CI: 0.33-5.37, P=0.70).


Conclusion
Pregnancy may not have significant effect on long-term cardiac function in PAH-CHD patients, but this conclusion needs to be confirmed by further studies.


Key words: 
Pregnancy; Hypertension, pulmonary; Prognosis; Cohort studies
合理进行调脂治疗 --由病例看指南
Authors: 史旭波, 胡大一
Journal: BMJ (2005)

例1 男,45岁,体检时发现低密度脂蛋白胆固醇(LDL-C)中度升高和高密度脂蛋白胆固醇(HDL-C)降低.空腹血脂检查:总胆固醇(TC)5.46 mmol/L(210 mg/dl),HDL-C 0.70 mmol/L(27 mg/dl),甘油三酯(TG)4.16 mmol/L(160 mg/dl),LDL-C 3.93 mmol/L(151 mg/dl).空腹血糖6.38 mmol/L(115 mg/dl).患者身高168 cm,体重85 kg,体重指数(BMI)30.1,腰围96.5 cm.平均每日吸烟20支.血压120/80 mm Hg(1 mm Hg=0.133 kPa).有早发冠心病家族史.患者不愿意服药治疗,而愿意进行治疗性生活方式改变,故医生要求其戒烟,减轻体重,严格控制饮食总热量,减少饱和脂肪酸、胆固醇和糖的摄入.随访发现,患者减少了吸烟量,并进行大运动量的锻炼,遵医嘱进行了饮食控制,但由于不能很好地减少总热量的摄入,因此体重并没有降低.其血脂指标有改善,3个月后检查结果显示 LDL-C 3.33 mmol/L(128 mg/dl),HDL-C 0.81 mmol/L(31 mg/dl),TG无明显变化,空腹血糖5.83 mmol/L(105 mg/dl).下一步如何治疗?
Interpretation of guideline for hierarchical diagnosis and treatment of diabetic retinopathy
Authors: Xiaohui Yang
Journal: BMJ (2017)

文章对《糖尿病视网膜病变分级诊疗技术方案》的制定背景和目的、糖尿病视网膜病变的筛查、诊疗、转诊流程、糖尿病视网膜病变患者的健康教育进行解读，明确在全科医生、内科医生或内分泌科医生和眼科医生一起组成的综合的医疗服务团队中，各级医疗机构与医务人员的职责，构建内科与眼科之间的双向转诊和分级诊疗体系，以更好地防治糖尿病视网膜病变。