tbuckley/cabot-search huggingface dataset:
A first-in-human phase I study in patients with advanced and/or refractory solid malignancies to evaluate the safety of ATOR-1015, a CTLA-4 x OX40 bispecific antibody.
Authors: Jeffrey Yachnin, Gustav J. Ullenhag, Ana Carneiro, Dorte Nielsen, Kristoffer Staal Rohrberg, Anne Månsson Kvarnhammar, Lena Schultz, Erika Bågeman, Camilla Wennersten, Charlotte Astrid Russell
Journal: Journal of Clinical Oncology (2020)

3061 Background: ATOR-1015 is a human CTLA-4 x OX40 targeting IgG1 bispecific antibody developed to be a next generation CTLA-4 antibody with enhanced immune activation and tumor-directed activity for improved efficacy and reduced toxicity. Methods: The primary objective of the study is to determine the maximum tolerated dose (MTD) and/or the recommended phase 2 dose (RP2D) in patients with advanced solid malignancies. Safety and tolerability of ATOR-1015 are assessed by adverse events (AEs), vital signs, ECG, laboratory evaluations and physical examinations. Secondary objectives include pharmacokinetics (PK), immunogenicity and clinical efficacy. Clinical efficacy is assessed using Response Evaluation Criteria in Solid Tumors for immune-based therapeutics (iRECIST). The study is designed with single patient cohorts for doses below 100 mg followed by a modified 3+3 design (NCT03782467). Intra-patient dose escalation is allowed. ATOR-1015 is administered intravenously every other week as a single agent until confirmed progressive disease, unacceptable toxicity or withdrawal of consent. Results: From March 2019 to February 2020, 15 patients have been exposed to ATOR-1015. The median age of the patients is 52 years (range 40-72). The following cancer types have been included: colorectal cancer (n=8), uveal melanoma (n=2), pancreatic cancer (n=2), ovarian cancer (n=2), and cholangiocarcinoma (n=1). Patients received a median of 6 prior lines of therapy (range 3-16). Dose levels from 0.043 mg to 200 mg have been evaluated and declared safe. Dose escalation is ongoing, and 400 mg is under evaluation. The median time on study was 8 weeks (range 2.1-34.3). Four patients are on study and eleven patients have discontinued treatment . Reasons for discontinuation include clinical deterioration (n=7), death due to disease progression (n=2), confirmed disease progression (n=1) and investigator´s decision (n=1). Six of the 15 patients experienced drug-related AEs which were grade 2 or less. Infusion-related reactions (IRR) were reported in four patients. One of those four also had abdominal pain and mediastinal burning sensation. The IRR symptoms were predominantly rash. One patient had vitiligo, and one had rash. No dose-limiting toxicities have occurred. Preliminary PK data show dose-proportional kinetics up to 200 mg. Conclusions: The dosing of ATOR-1015 has been safe and well-tolerated up to 200 mg. Dose escalation continues and the current dose level under evaluation is 400 mg. Clinical trial information: NCT03782467 .
Real-life implementation of the SCOT trial findings: An interrupted time series analysis.
Authors: Catherine Hanna, Jose Antonio Robles-Zurita, Philip McLoone, Caroline Kelly, Kathleen Boyd, Robert J. Jones
Journal: Journal of Clinical Oncology (2020)

e19341 Background: The Short Course Oncology Treatment (SCOT) trial demonstrated that three months of adjuvant, doublet chemotherapy for patients with colorectal cancer was non-inferior and significantly less toxic than six months. To understand if and how these results were implemented, this study analysed prescribing practice before and after dissemination of the SCOT results at a population level. Methods: Individual electronic records for patients in a Scottish health board (population 1.1 million) were reviewed (January 2010-June 2019) to explore the proportion of patients receiving over three months of treatment pre and post-SCOT. Logistic and linear regression were used in an interrupted time series analysis to estimate prescribing practices, and to assess the counterfactual situation in which the trial had not occurred. Patients receiving single agent chemotherapy were the comparator group. Predictors of patients receiving a longer duration of treatment post-SCOT were also identified. Results: In total, 998 patients received adjuvant chemotherapy; 564 doublet and 434 single agent. For those prescribed doublet chemotherapy, there was a significant decrease in the proportion receiving more than 3 months of treatment after the SCOT trial results (20%) versus pre-SCOT (84%, p &lt; 0.001). Disease risk was a key predictor for longer duration of treatment post-SCOT. Table outlines the predicted practice post-SCOT (June 2019) for the modelled and counterfactual scenarios. Conclusions: A clear change in treatment duration for patients receiving doublet chemotherapy was observed. Disease stage influencing post-SCOT prescribing aligns with recently updated clinical guidelines. This methodology can be applied to explore the implementation of future trials and to highlight any barriers to implementation that exist. [Table: see text]
Covid-19: Review of ethnic disparities is labelled “whitewash” for lack of recommendations
Authors: Gareth Iacobucci
Journal: BMJ (2020)

People from ethnic minority backgrounds are more likely to have covid-19 diagnosed and to die from it, a review from Public Health England has confirmed.1

But the report was described as “a missed opportunity” by medical leaders because of its lack of recommendations for reducing these disparities. This is despite the review being commissioned amid concerns about the disproportionate impact of covid-19 on ethnic minorities, and its terms of reference stated that it would make recommendations for further action.2

Chaand Nagpaul, BMA council chair, said that the statistical analysis, although important, “gets us no closer towards taking action that avoids harm to black and minority ethnic communities.”

He added, “The BMA and the wider community were hoping for a clear action plan to tackle the issues, not a reiteration of what we already know. We need practical guidance, particularly in relation to how healthcare workers and others working in public …
居民健康档案建立和使用中的经验与问题
Authors: 周涛
Journal: BMJ (2010)

建立居民健康档案的便捷主要体现在电话通知、电话询问、上门服务、有急事时快速查阅,还有就是在个人健康档案的基础上根据户主、户口本编号、户主与本人的关系三项自动生成家庭档案.举例说明它的便捷:2008年10月份东城区疾病预防控制中心要求我们所有社区站1周内完成50户的家庭保健员入户控油盐摸底情况调查,我在当时又有个会议必须要去参加,迫使我在2天内必须完成15户的入户调查工作。
健康管理是科学理性应对甲型H1N1流行性感冒第二波的最好武器
Authors: 黄建始
Journal: BMJ (2009)

新型甲型H1N1流行性感冒(甲流)的第二波兵临城下,流感样病例大增,其死亡病例引起不少人的担忧,大家实实在在地感受到狼来了的气氛.如何应对?我认为健康管理是科学理性应对甲流第二波最好的武器。
Real-world practice patterns and barriers to quality care in acute myeloid leukemia (AML).
Authors: Maen A. Hussein, Taral Patel, Pavani Ellipeddi, Breanne Farris, Rebecca R Crawford, Jeffrey D. Carter, Tamar Sapir, Eunice S. Wang
Journal: Journal of Clinical Oncology (2020)

e19172 Background: For AML patients who are ineligible for intensive induction, novel therapies have greatly improved treatment options, though practice challenges individualizing care have hindered effective integration. In a quality improvement (QI) program conducted in 3 community oncology systems, we assessed practice patterns and barriers involving the use of novel therapies for AML. Methods: We surveyed 15 hematology team members to assess barriers to quality AML care and audited electronic medical records (EMR) of 100 patients across 3 community oncology centers. EMR demographics, disease characteristics, and treatment selection were reviewed. To address suboptimal guideline-aligned care, teams participated in audit-feedback sessions to develop action plans for resolving identified gaps. Results: The EMR audit demonstrated a lack of documentation for clinically important metrics necessary for individualized treatment selection and monitoring, including performance status and testing for targetable biomarkers (Table). Additionally, there was low documented use of novel therapies, such as venetoclax and gemtuzumab ozogamicin (GO), and no documented use of FLT3 or IDH inhibitors. Further, the audit revealed low adherence to guideline recommendations for frontline regimens – notably, 33.3% patients with FLT3 or IDH mutations (n = 15) were receiving low dose cytarabine alone, and 50% patients with a documented performance status of 3+ (n = 2) received intensive induction therapy. Survey findings indicated very low or low confidence in aligning practice with guidelines (20%), identifying patients who are not candidates for intensive induction (27%), and ordering/interpreting molecular tests (33%). Appropriate treatment selection (47%) and integration of molecular testing (27%) were reported as top challenges for individualized AML care. During audit-feedback sessions, teams identified improved collaboration with hematopathologists, assessment of patient mutational status, and patient engagement in treatment planning as actions they plan to integrate. Conclusions: These findings reveal important performance gaps in individualized AML care in community settings, which may inform future QI initiatives. [Table: see text]
手术治疗关节内跟骨骨折65例
Authors: 袁福禄, 韩广普, 许俊岭, 李晓明, 石国君, 张洪相
Journal: BMJ (2005)

跟骨骨折占所有足部骨折的60%,70%的跟骨骨折为关节内骨折[1].随着CT技术、术中透视技术、内固定技术的应用,对跟骨关节内骨折的认识和治疗取得了较大进展.我院1996年1月至2003年12月手术治疗65例关节内跟骨骨折,疗效较满意,现报告如下. 1.对象与方法:男48例,女17例;年龄20～66岁,平均36岁.均为单足跟骨骨折,按Sanders分型[2]:Ⅱ型25足,Ⅲ型26足,Ⅳ型14足.受伤原因:坠落伤41例,车祸伤20例,砸压伤4例。
Sipuleucel-T (sip-T) and oral androgen axis inhibitors in black men being treated for metastatic castration-resistance prostate cancer (mCRPC): Observations from the Medicare Fee for Service (FFS) population.
Authors: Hala Borno, Kelvin A. Moses, Paul Monk, Kate Fitch, Matthew Harmon, Scott Flanders, Rana R. McKay
Journal: Journal of Clinical Oncology (2020)

e17589 Background: Black men historically have been underrepresented in clinical trials, contributing to poor understanding of potential race-based differences in prostate cancer care and biology. This retrospective, real world analysis examines survival outcomes in black men who received sip-T or oral agents like abiraterone or enzalutamide for mCRPC. Methods: Using Medicare Fee for Service Identifiable Research data, we identified racially black men with a qualifying prostate cancer diagnosis (ICD-9 185, ICD-10 C-61) and an initial drug claim for treatment (abiraterone acetate, cabazitaxel, docetaxel, enzalutamide, radium-223, or sip-T) in 2014 or 2015. Continuous Part A, B, and D eligibility and no HMO enrollment were required for 24 months or until death per Social Security Death Index. We compared outcomes in black patients who received sip-T at any time vs those who received an oral agent in any line and no sip-T. Survival was estimated using the Kaplan-Meier method (unadjusted) and hazard ratios using Cox proportional hazards regression. Results: Of 14,456 patients identified in 2014 and 2015, 1603 were racially black. Among eligible men, 140 received sip-T and 1266 received an oral agent. At 24 months, 76% of men who received sip-T were still alive compared with 49% of those who received the oral agents (Table). Median OS was not estimable in men who received sip-T but was 23.1 months (95% CI: 21.6, NE) in those who received oral agents (Table). In a univariate model, use of sip-T resulted in a 63% reduction in risk of death compared to never receiving sip-T (HR, 0.37 [95% CI, 0.26, 0.52], P &lt; 0.0001). Conclusions: In this real world analysis of black mCRPC patients, sip-T at any point was associated with longer OS over those receiving the oral agents without ever receiving sip-T. Development of a multivariate model is planned. [Table: see text]
Efficacy of WC03 in treating radiotherapy-induced oral mucositis (RIOM): A multicenter nonrandomized controlled clinical trial.
Authors: Dongmei Chen, Tian Gu, Liqun Jia
Journal: Journal of Clinical Oncology (2020)

e24127 Background: RIOM is a common side effect of radiotherapy for head and neck cancer patients, however, no standard and effective treatment existed so far. WC03 is an oily Traditional Chinese Herbal Medicine recipe for external-use in mouth, which had been utilized to treat RIOM in China-Japan Friendship Hospital for more than ten years. This trial aimed to investigate the safety and efficacy of WC03 in treating RIOM. Methods: Between May 2017 and June 2018, we conducted a multicenter, non-randomized controlled trial within 7 hospitals in China. Inclusion criteria included head and neck cancer patients who developed RIOM (≥ grade II) undergoing radiotherapy or after radiotherapy (within 6 months). They were assigned to different groups based on their willingness. Patients in treatment group were treated by WC03, which was daily applied to the oral mucosa for 30 min twice a day. Patients in control group were treated with Kangfuxin (Periplaneta americana) Lotion combined with conventional treatment such as vitamin B12 and rhGM-CSF. The interventions lasted for 2 weeks. The primary outcome was overall effective rate, which was calculated through changes of radio-induced oral mucositis grade before and after interventions (according to National Cancer Institute Common Toxicity Criteria). Secondary outcome was oral pain which was measured by Numeric Pain Rating Scale. Results: 48 eligible participants were enrolled, 24 in treatment group and 24 in control group, respectively. 2 patients in treatment group were withdrawn from the study in the first week because of developing secondary infection and treatment got changed. Thus, 22 were included at the terminal of the study. All the 24 participants in control group were included. After the intervention, the overall effective rate was 95.45%(21/22) in the treatment group, which was significantly higher than that of 70.83% (17/24) in the control group (p = 0.049). Similarly, 86.36%(19/22) of the participants in treatment group got cured, which was significantly higher than that of 45.83%(11/24) in the control group(p = 0.007). There is a trend that oral pain relief rate in the treatment group was higher than that of the control group, but not statistically significant (100.00% vs. 87.50%, p = 0.210). Patients in treatment group used less time to get relieved from RIOM than control group (5 vs. 8 days, p &lt; 0.001). No adverse event had been observed in both two groups. Conclusions: WC03 is safe and effective in treating radiotherapy-induced oral mucositis. RCT is necessary in future studies.
Excessive mortality in 1,353 five-year survivors of nasopharyngeal cancer.
Authors: Chi Leung Chiang, Ching Lung Cheung, James Philip Hingley, Chor Wing Sing, Ka Shun Fong, Tai Chung Lam, Victor Ho-Fun Lee, Kwok Hung Au, James Chung-Hang Chow, Yin Ting Cheung, Roger Kai-Cheong Ngan, Cheuk-Wai Choi, Anne WM Lee, Ian Chi Kei Wong
Journal: Journal of Clinical Oncology (2020)

e24090 Background: Survival of NPC patients has improved in past decades. Yet, survivors continue to face elevated risks of life-threatening late effects. Their impact on late mortality remains poorly quantified. Methods: 1353 five-year NPC survivors diagnosed between 1997 and 2013 at Queen Mary Hospital were reviewed. Their demographics and treatment data were taken from electronic medical records. Survival probability, standardized mortality ratios (SMRs) and absolute excessive risk were calculated for overall and cause-specific deaths. Results: At median follow-up time of 12.4 years, 412 (30.5%) five-year survivors had died at the time of analysis. 66.2% of deaths attributed to non-recurrence death. Estimated 10-, 15-, and 20-year survival probability were 81.4%, 67.6%, and 57.3% respectively. Compared to Hong Kong general population, absolute excessive risk of death from any causes was 17 deaths per 1000 person-years; overall SMR was 3.52 (95% CI: 3.19 to 3.87, p&lt;0.001). Increases in cause-specific mortality were seen for death due to pulmonary (SMR: 6.75; 95% CI: 5.67 to 7.98) and secondary malignancy (SMR: 1.41; 95% CI: 1.06 to 1.83). Conclusions: Five-year NPC survivors still face excessive mortality long after diagnosis, and majority of death was from non-recurrence death. Further analyses are needed to determine predictive factors of excessive mortality. [Table: see text]
Computational pathological identification of prostate cancer following neoadjuvant treatment.
Authors: Belma Dogdas, Christopher Kanan, Patricia Raciti, Shaozhou Ken Tian, Sabine Doris Brookman-May, Lisa Wetherhold, Andressa Smith, Oliver Brendan Rooney, Sharon Anne McCarthy, John David Alvarez, Angela Lopez-Gitlitz, Adam Casson, Ran Godrich, Jeremy D. Kunz, Rodrigo Ceballos, Carla Leibowitz, Leo Grady, Thomas J. Fuchs
Journal: Journal of Clinical Oncology (2020)

e14052 Background: The need for accurate pathological identification and quantitation of prostate cancer (PC) following neoadjuvant treatment with androgen deprivation therapy (ADT) and androgen receptor antagonists is increasing as PC treatment continues to evolve. In clinical practice, pathological assessment of residual tumor is a tedious and time-consuming process due to the volume of tissue from radical prostatectomy (RP). In addition, neoadjuvant treatments can greatly alter both benign and neoplastic prostate tissue morphology making the pathology assessment difficult for even specialized pathologists. Paige Prostate 1.0 is a clinical-grade artificial intelligence (AI) system for PC detection. It was trained and evaluated in over 50,000 prostate biopsy slides with validation across more than 800 institutions worldwide using multiple slide scanners. Methods: We evaluated the performance of Paige Prostate 1.0 at identifying prostatic tumor on 64 hematoxylin and eosin stained slides exhibiting neoadjuvant treatment effect from apalutamide, enzalutamide, and/or ADT. Results: Analysis of the receiver operating characteristic curve demonstrated an area under the curve of 0.96. Using the Paige Prostate 1.0 operating point, it achieved a sensitivity of 91% and a specificity of 94%, corresponding to the correct identification of challenging treated morphology in 59/64 slides using expert pathologists as the reference. False negative cases were typically represented by atypical small acinar proliferation that required expert pathological consensus confirmation. Conclusions: To our knowledge, this is the first AI based evaluation of residual disease in PC with hormone neoadjuvant therapy. Paige Prostate 1.0 effectively identified tumor despite treatment effects. Future work will include optimization of Paige Prostate 1.0 by training with RP specimens from a larger cohort of appropriate samples, as well as precise measurement of residual tumor burden to further improve its accuracy and reproducibility. Paige prostate residual disease detection 1.0 has the potential to impact emerging clinical practice at the patient level and to complement the pathological assessment of RPs in global phase 3 clinical trials, such as PROTEUS, in a standardized, reproducible, and robust way.
The effect of intrauterine device application on post-menopausal reproductive health
Authors: Xiaohua Zhang, Liping Xiao, Haoping Zhu
Journal: BMJ (2014)

To explore the potential effects of intrauterine device (IUD) usage in reproductive ages on women's postmenopausal reproductive health. Women in Shanghai Minhang district were enrolled and categorized into group Ⅰ (IUD), group Ⅱ (tubal ligation) and control group (external ejaculation). Their data were collected and analyzed retrospectively. A total of 2 744 women during postmenopausal period were enrolled (group Ⅰ=2 253, group Ⅱ=202, control=289). Pearl index of each group was 1.08 (group Ⅰ), 0.00 (group Ⅱ) and 15.22 (control), respectively. Women with IUD usage in reproductive ages were less likely to develop reproductive benign diseases after menopause (χ2=67.51, P=0.00, OR=0.44, 95%CI: 0.32-0.59). Logistic regression indicated pregnancy history (OR=3.85), child-bearing history (OR=0.52), IUD usage (OR=0.48), tubal ligation (OR=1.74), longer duration using contraceptive methods(OR=0.99), contraception failure(OR=1.74)and family planning surgical procedures(OR=1.73)were risk factors for reproductive benign diseases after menopause. IUD utility in reproductive ages may reduce the risks of benign diseases in reproductive system for postmenopausal women.


Key words: 
Intrauterine device; Postmenopausal period
A retrospective study of immunochemical fecal occult blood test for colorectal tumor screening among gastroenterology outpatients
Authors: Ying-yun Yang, Dong Wu, Jing-nan Li, Jia-ming Qian
Journal: BMJ (2012)

Objective To evaluate the application of immunochemical fecal occult blood test for colorectal cancer screening in a gastroenterology clinic. Methods Total 512 outpatients received immunochemical fecal occult blood tests and colonoscopy for screening of colorectal cancer from January 2009 to October 2010 in Gastroenterology Clinic of Peking Union Hospital.The application of occult blood test was retrospectively evaluated using colonoscopy and pathological examination as the gold standard. Results Among 512 patients,203 were found positive for immunochemical fecal occult blood. According to the colonoscopy and histological study,115 patients had polyps,9 with high-grade dysplasia and 21 with colorectal cancer.The sensitivity,specificity,positive likelihood ratio and negative likelihood ratio of fecal occult blood to detect colorectal adenomatous polyps was 42.8％,60.9％,1.09 and 0.93,respectively.And those for detection of colorectal cancer and high-grade dysplasia were 76.6％,62.5％,2.05 and 0.37,respectively.Conclusions Immunochemical fecal occult blood test was useful in the screening for colorectal tumors among gastroenterology clinic patients.More large-scale prospective studies are needed to establish a screening model for colorectal tumors.

Key words: 
Occult blood;  Intestinal neoplasms ;  Diagnosis
Helicobacter pylori infection in Lhasa People's Hospital from 2009 to 2013
Authors: Ye Zong, null Basangzhuoma, null Yibiranhen
Journal: BMJ (2015)

Objective
To investigate the infection status of Helicobacter pylori (Hp) in a Lhasa hospital.


Methods
A retrospective survey of Hp infection from 2009 to 2013 was conducted in Lhasa People's Hospital. The data of 14C-urea breath test and gastroscopy were analyzed.


Results
A total of 2 908 patients were enrolled, 1 518 (52.20%) were Hp positive, including 1 061 males (1 061/1 939, 54.72%) and 457 females (457/969, 47.16%). The Hp infection rate in males was higher than that in females (χ2=14.788, P= 0.000). The Hp infection rate by years from 2009 to 2013 was 55.97%(267/477), 49.79%(239/480), 54.66%(375/686), 52.06%(291/559) and 49.15%(347/706), respectively. The infection rate in 2013 was significantly lower than that in 2009 and 2011 (P=0.021, 0.040). There were no significant differences in Hp infection rates among Tibetan, Han and Hui ethnic groups. In 2020 cases who underwent endoscopic examination, 1 098 had Hp positive (54.36%). The Hp infection rate in chronic superficial gastritis group(39.91%) was significantly lower than that in erosive gastritis (χ2=30.143, P=0.000), gastric ulcer (χ2=22.434, P=0.000), gastric polyps (χ2=9.627, P=0.002), gastric cancer (χ2=9.506, P=0.002), duodenal ulcer (χ2=54.158, P=0.000), duodenitis (χ2=14.966, P=0.000) and compound ulcer groups (χ2=8.582, P=0.003). The Hp infection rate in duodenal ulcer group(68.42%) was significantly higher than that in chronic superficial gastritis (χ2=54.158, P=0.000), erosive gastritis (χ2=6.733, P=0.009), atrophic gastritis (χ2=21.496, P=0.000) and gastric ulcer groups (χ2=8.940, P=0.003).


Conclusion
Hp infection rate appears a decreasing trend in Lhasa area in last 5 years; among various gastro-duodenal diseases patients with duodenal ulcer have a highest Hp infection rate.


Key words: 
Helicobacter pylori; Gastrointestinal diseases; Retrospective studies