tbuckley/cabot-search huggingface dataset:
Novel targeted and sustained drug delivery therapy for localized pancreatic cancer: Validation in porcine models and minimally invasive surgical feasibility in human cadavers.
Authors: Margaret Lashof-Sullivan, Michael Paul Kim, Ching-Wei David Tzeng, Laura Indolfi
Journal: Journal of Clinical Oncology (2020)

e16747 Background: As systemic therapy improves, control of localized pancreatic adenocarcinoma (PDAC) remains a major challenge. Up to 40% of patients present with locally advanced and borderline resectable tumors, for whom enhanced local downsizing of disease could improve resection rates and survival. PanTher is developing a locally targeted drug delivery product (PTM-101) to treat localized PDAC by directly delivering chemotherapy to the primary tumor. PTM-101 is a bioresorbable polymeric patch containing paclitaxel surgically placed onto the tumor. It biodegrades, resulting in sustained localized release of drug. In murine orthotopic patient-derived xenograft models a 60% increase in OS and inhibition of metastasis was achieved after single treatment. Here we validate and de-risk PTM-101 implantation in standard OR settings in large animals and human cadavers to prepare for a phase 1 study. Methods: We conducted two 30-day studies in porcine models to assess safety, toxicity and biodistribution. Parameters included body weights, hematology, urinalyses, drug levels in the blood and at the implantation site and histomorphologic evaluation. To validate the feasibility of minimally invasive surgical insertion, we conducted a follow-up study in three human cadavers. In each case, PTM-101 was laparoscopically placed directly on the pancreas. Results: We surgically implanted PTM-101 without complications and our approach ensures localized drug delivery with extreme control of drug biodistribution. Importantly, no detectable levels of drug were present in the blood any time during the 30-day treatment, confirming our targeted delivery. PTM-101 was consistently and effectively placed during a minimally invasive surgery without substantial increase in procedure time. PTM-101 conforms fully to pancreatic tissue, allowing for close contact with the intended tissue for drug delivery, and can cover the areas of the pancreas where critical involvements of tumors with vasculature are commonly found. Conclusions: By changing the route of administration to target just the area of interest, PTM-101 can increase the amount of drug reaching the tumor with the aim to enhance therapeutic efficacy. This could open the door to clinically relevant applications in PDAC patients: (i)pre-operatively as neoadjuvant treatment to control progression and downsize locally advanced and borderline anatomy to improve resectability; or (ii)post-resection to reduce the rate of local recurrence.
Timing of assessments for PRO measures in advanced RCC clinical trials.
Authors: Sundeep Agrawal, Joyce Cheng, Vishal Bhatnagar, Bellinda King-Kallimanis, Richard Pazdur, Paul Gustav Kluetz
Journal: Journal of Clinical Oncology (2020)

e19101 Background: Efficient and thoughtful collection of PROs in randomized cancer trials is necessary, especially when comparing drugs with differing administration schedules. Assessment timing for PROs can dramatically influence results. We sought to better understand how different assessment schedules affect interpretation of toxicity using PRO data. Methods: We reviewed 3 randomized trials in advanced/metastatic RCC with a control arm of sunitinib administered 4 weeks on/2 weeks off. All 3 trials used FACT Kidney Symptom Index (FKSI-19 or -DRS) and one also used EORTC QLQ-C30. For each trial, we chose patient-reported diarrhea and bone pain due to their strong association with the therapeutic intervention and the disease, respectively. Results: For the first 12 weeks, all trials had PRO assessments at baseline but had differing schedules thereafter. PRO assessment in Trial 1 was every 3 weeks; Trial 2: week 6 and week 12; Trial 3: every 3 weeks on the investigational arm and at weeks 4, 6, 10 and 12 on the sunitinib arm. Notably, all assessments for Trial 2 were after 2-week sunitinib washout while Trials 1 and 3 had assessments before and after washout. The table shows the percentage of patients who experienced any worsening from baseline in diarrhea and bone pain in the first 2 assessments. In each trial, more patients had worsening following periods of treatment versus washout on the sunitinib arm, with no such fluctuation on the non-sunitinib arms. The pattern was more apparent for diarrhea (treatment-related) than for bone pain (disease-related). Conclusions: Patients’ recall of symptoms may vary depending on the timing of PRO assessments in relation to drug administration and may be more prominent with respect to treatment-related symptoms, as disease-related symptoms are less impacted by drug toxicity and washout. Clinical protocols should carefully consider PRO assessment timing in relation to drug administration to improve interpretation of toxicity. Higher fidelity PRO data can be obtained with weekly collection of symptoms during the first few months of cancer clinical trials. [Table: see text]
A preliminary study on the management pathway of atherosclerotic cardiovascular diseases in primary care based on clinical pathway theories
Authors: Rongrong Wan, Kai Yu, Shuang Wang, Lu Zhang, Shuguang He, Xin Zhao, Huan Xiao, Xue Lin, Xuejun Liu, Xiaosong Yu
Journal: BMJ (2017)

Objective
To evaluate the feasibility and effectiveness of the management pathway of atherosclerotic cardiovascular disease (ASCVD) .


Methods
One hundred and twenty two elderly patients with more than one ASCVD risk factors contracting general practice service in Changbai Community Health Center of Shenyang Municipality were enrolled. The management pathway of ASCVD was conducted with a integrated  model based on the self-control study design. The effects were evaluated with Hibbard′s Patient Activation Measure (PAM) after 6 months of intervention.


Results
After 6 months, 9 participants dropped out of study (7.4%). The questionnaire survey was conducted in 113 participants and the response rate was 100%. After intervention, the overall level of activation in participants was increased(t=5.809, P<0.05). The scores of four stages of activation were increased: believing the importance of active role(t=4.546, P<0.05), confidence and knowledge of taking action (t=4.684, P<0.05), taking action(t=5.332, P<0.05), staying the course under stress (t=7.785, P<0.05). The total scores (t=2.086, P<0.05) and the scores of mental component summary (t=1.980, P<0.05), physical function (t=2.420, P<0.05), vitality (t=3.077, P<0.05), mental health (t=2.992, P<0.05) in SF-36 were increased. The activation of patients was significantly correlated with the quality of life (r=0.320, P<0.05). After intervention, the blood pressure, HbA1c, blood lipid levels trended to be decreased, and the diastolic blood pressure was significantly decreased after  (t=2.015, P<0.05).


Conclusion
The ASCVD management pathway andintegrated intervention model in primary care is feasible and effective. After the implementation, the activation of patients is increased, the quality of life and clinical outcomes are improved in different degrees.


Key words: 
Disease management; Clinical pathway; Atherosclerotic cardiovascular diseases
Prexasertib, a cell cycle checkpoint kinase 1 inhibitor, in <i>BRCA</i> mutant recurrent high-grade serous ovarian cancer (HGSOC): A proof-of-concept single arm phase II study.
Authors: Erika Joelle Lampert, Daniel An, Ann McCoy, Elise C. Kohn, Christina M. Annunziata, Kathryn Trewhitt, Alexandra Dos Santos Zimmer, Stanley Lipkowitz, Jung-min Lee
Journal: Journal of Clinical Oncology (2020)

6038 Background: Preclinical data suggest cell cycle checkpoint inhibition induces greater cell death in BRCA mutant HGSOC by causing replication stress and dysregulation of DNA damage responses. We hypothesized that prexasertib, a cell cycle checkpoint kinase 1 (CHK1) inhibitor, would be active in BRCA mutated HGSOC patients. Methods: We conducted a single center, two-stage phase II study of prexasertib (105mg/m 2 IV every 2 weeks) in HGSOC patients with known germline or somatic BRCA mutations. The primary endpoint was RECIST response rate (RR). Progression-free survival (PFS) and safety (CTCAE v4) were secondary endpoints. Baseline research biopsies and blood samples were collected for exploratory biomarker endpoints. Results: Between February 2015 and July 2019, 22 heavily pretreated (median 5 prior systemic therapies [1-12]) women with BRCA mutant HGSOC (median age 58.7 [44-74.8]) received at least one dose of prexasertib. 13 (59%) patients were secondary platinum-resistant (median 8 [3-12] prior therapies) and 9 (41%) maintained platinum-sensitivity (median 4 [1-5] prior therapies). All but one received prior PARP inhibitor (PARPi) either in combination (10 [48%]) or as monotherapy (11 [52%]), with a median 5 month [mo; 1-29] PARPi-free interval prior to study entry. There was one complete response (41+mo, platinum-sensitive, no prior PARPi) and one partial response (9+mo, platinum-sensitive, 13.5mo PARPi-free interval) yielding an 11% RR (2/18 evaluable). No response was seen in platinum-resistant patients with prior PARPi. Median duration on study treatment was 4mo [1-9] among 21 patients with prior PARPi and 4mo [1.5-9] among 17 evaluable patients with prior PARPi. Common (&gt;10%) grade 3/4 adverse events were neutropenia (82%), leukopenia (64%), and thrombocytopenia (14%); only one patient had grade 3 febrile neutropenia. 16 of 18 (89%) patients with grade 3/4 neutropenia received prophylactic growth factors for subsequent treatments. Conclusions: Prexasertib is tolerable and has modest activity in heavily pretreated BRCA mutant HGSOC patients. Further evaluation of predictive biomarkers for exceptional responders is ongoing. Clinical trial information: NCT02203513.
心搏骤停的院前急救--基本生命体征的维护
Authors: 冯庚
Journal: BMJ (2005)

对心搏骤停患者实施心肺脑复苏的治疗目标和要点:①恢复患者的自主循环,主要措施有电击复律、胸外心脏按压、人工呼吸和供氧;②脑保护和脑复苏,最大限度地恢复脑组织的功能,主要措施有强化脑部血供、降温疗法、降低脑代谢和对抗自由基的药物疗法等;③维持患者的基本生命体征,包括呼吸、血压、心律和电解质平衡等,主要措施有各种相关药物的应用.呼吸的建立和维护已经在前面的讲座介绍,本文重点讨论血压、心律和电解质平衡的维护。
Implementation of psychosocial support project in a pediatric oncology camping program.
Authors: Simone Lehwess Mozzilli, Marina Salvetti, Maria Fernanda Manhaes, Regina Szylit, Mariana Freitas, Fernanda Rafaela Garcia
Journal: Journal of Clinical Oncology (2020)

e22534 Background: The oncological treatment can generate psychosocial distress for patients and their families. The Beaba Camping aims to educate and empower patients and caregivers through Technology Information and Gamification. In August 2019, in the third edition of the project, a pilot of Psychosocial Support Program was implemented to provide an integrative care to 71 children and adolescents under cancer treatment and 68 caregivers. Methods: Five psychologists, specialized in paediatric psycho oncology and palliative care, were selected to structure the Psychosocial Support Program and conduct interventions during three days of the camping. Based on evidences and experiences, the psychologists divided the interventions in: 1. Individually - children and adolescents. 2. Group - caregivers: 2.1. Belonging: identification and recognition of peers. Identification of psychological distress and similar fears; 2.2. Psychological Group Intervention: creation of groups to facilitate the intervention and bonding; 2.3. Feeling of the Day: expression of which emotion was the most prevalent each day of camping; 2.4. A Word of Support: exchange supportive statements among the peers. Results: 20 children/adolescents and 19 caregivers were attended individually, with demands variating from: Anxiety and sadness; Fear of future and prognosis; Social isolation and adaptation. 68 adults participated in groups that brought discussions involving: Biggest fears and difficult moments of the treatment; Relationship with their children and adolescents; Coping strategies and spirituality. Conclusions: The Psychosocial Support is an important and essential part of the cancer treatment. The Camping with Psychosocial Support Program may enable the demystification of the role of the psychologist, the link between professionals and patients and their caregivers, the binding among peers and the education about how the psychosocial support can be helpful to everyone involved in the treatment. For future improvements, more psychologists will participate in order to attend a larger number of participants and to perform more group interventions, including with children and adolescents.
Effects of long-term combined estradiol and progesterone therapy on bone mineral density in patients with Turner syndrome
Authors: Ling Hu, Jie Qin, Kun Lei, Ping-an Yang, Jiang-feng Mao
Journal: BMJ (2011)

The ptrpose of this study was to investigate the effects of long-term estradiol and progesterone combined therapy on bone mineral density (BMD) in patients with Turner syndrome.Eight patients with Turner syndrome received estradiol and progesterone combined therapy for six years were observed and BMD was measured for each of them before hormone replacement therapy (HRT) and at an interval of one to two years after HRT and compared with that in normal age-sex matched women.BMD was significantly lower in patients with Turner syndrome than that in normal controls before HRT.All the patients with Turner syndrome had breast enlargement and irregular vaginal bleeding after HRT.BMD increased slightly in the patients with Turner syndrome after six-year HRT ,but still much lower than that in normal controls.Their BMD of the 2nd to 4th lumbar vertebra increased to (0.84±0.22) g/cm2 after HRT from (0.75±0.12)g/cm2 before it,with Z-score increased to -2.2±0.6 from -3.2±0.9,respectively; and overall BMD of the hip increased to (0.81±0.08) g/cm2 after HRT from (0.68±0.07) g/cm2 before it,with Z-score increased to-1.2 ± 0.3 from-2.2 ± 0.5,respectively.Long-term HRT can improve their BMD for patients with Turner syndrome but can not restore it to normal.

Key words: 
Turner syndrome; Bone density
Pancreatic solid pseudopapillary neoplasm in pediatric patients: report of 4 cases
Authors: Zheng Zhao, Zenghui Hao, Hui Miao
Journal: BMJ (2017)

The clinical data and follow-up information of 4 pediatric patients with pancreatic solid pseudopapillary neoplasm (SPN) admitted in the First Affiliated Hospital of Harbin Medical University between January 2000 and January 2016 were retrospective reviewed. Four patients were all girls aged 8-13 years. All cases were treated with surgical resection and the diagnosis was confirmed histopathologically. Patients were followed up for up to 6 years, and there was no recurrence detected. Pancreatic SPN in children is a potentially malignant borderline tumor. Complete surgical resection is the only option for this disease, and spleen preserving pancreatectomy is the first choice of operation with satisfactory results.


Key words: 
Pancreatic neoplasms; Pathological conditions, signs and symptoms; Child; Solid pseudopapillary neoplasms
以三级医院专家教学强化社区全科医师岗位培训
Authors: 王丽萍, 和立, 孙金翔
Journal: BMJ (2007)

众所周知,制约我国社区卫生服务能力的一大因素是合格的全科医师奇缺,不仅数量上难以满足要求,服务能力也难以得到群众认可.时至今日,全科医师的培训教育成了我国健全和完善社区卫生人才培训体系的重要环节[1]。
Image-guided navigation for locally advanced primary and locally recurrent rectal cancer: Evaluation of its early cost-effectiveness.
Authors: Melanie Lindenberg, Astrid Kramer, Esther Kok, Valesca P. Retel, Theo Ruers, Wim van Harten
Journal: Journal of Clinical Oncology (2020)

e16015 Background: Radical resection is an important prognostic factor in patients with locally advanced primary (LARC) and locally recurrent rectal cancer (LRRC), but achieving this can be challenging. Therefore, an intraoperative surgical navigation system has been developed, showing improved radical resection rates for LARC and LRRC. This study evaluates the early cost-effectiveness of navigated surgery in LARC and LRRC compared to standard surgery. Methods: Two Markov decision models; one for each indication, were used to estimate the expected costs and outcomes for navigated and standard surgery from a Dutch healthcare perspective over a 3-year time horizon. The models started with a decision tree resulting in a radical or non-radical resection. Subsequently, the Markov-models comprised the health states “stable disease”, “progression” and “death”. The input parameters were based on prospective (navigation cohort n = 33) and retrospective (control group n = 142) data collected at the Netherlands Cancer Institute, reference and unit prices and expert opinion. Quality-Adjusted Life Years (QALYs) were measured by the EQ5D-5L. Additionally, a probabilistic sensitivity analysis and a scenario analysis were performed. Results: Navigated surgery showed incremental costs of €3139 and €2857 in LARC and LRRC, respectively. For LARC, for navigation and standard surgery we found: 2.54 vs 2.52 Life Years (LYs), and 2.06 vs 2.04 QALYs. For LRRC we found 2.17 vs 2.11 LYs and 1.73 vs 1.67 QALYs. The base case analysis showed an Incremental Cost-Effectiveness Ratio (ICER) of €144,192 for LARC and €51,802 for LRRC per QALY gained. At a willingness to pay threshold of €80,000, navigated surgery is not cost- effective in LARC but is cost-effective in LRRC. When a hospital lacks a hybrid OR and needs to invest in one to use the navigation system, which will increase the ICERs for both indications. Finally, more utilization of the navigation system (12% to 50% utilization rate) shows ICERs of € 65,257 and €20,648 for LARC and LRRC, respectively. Conclusions: Based on the current data, the navigation system is expected to be cost-effective in LRRC and has the potential to become cost-effective in LARC. To decrease the costs, it is crucial to identify more surgical indications for image-guided navigation. Especially as in the near future, image-guided surgery is expected to be a standard option in surgical practice. As these findings are sensitive to uncertainty in the data, a randomized controlled trial is advised to perform for relevant indications.
Reporting and Implementing Interventions Involving Machine Learning and Artificial Intelligence
Authors: David W. Bates, Andrew Auerbach, Peter Schulam, Adam Wright, Suchi Saria
Journal: Annals of Internal Medicine (2020)

Increasingly, interventions aimed at improving care are likely to use such technologies as machine learning and artificial intelligence. However, health care has been relatively late to adopt them. This article provides clinical examples in which machine learning and artificial intelligence are already in use in health care and appear to deliver benefit. Three key bottlenecks toward increasing the pace of diffusion and adoption are methodological issues in evaluation of artificial intelligence-based interventions, reporting standards to enable assessment of model performance, and issues that need to be addressed for an institution to adopt these interventions. Methodological best practices will include external validation, ideally at a different site; use of proactive learning algorithms to correct for site-specific biases and increase robustness as algorithms are deployed across multiple sites; addressing subgroup performance; and communicating to providers the uncertainty of predictions. Regarding reporting, especially important issues are the extent to which implementing standardized approaches for introducing clinical decision support has been followed, describing the data sources, reporting on data assumptions, and addressing biases. Although most health care organizations in the United States have adopted electronic health records, they may be ill prepared to adopt machine learning and artificial intelligence. Several steps can enable this: preparing data, developing tools to get suggestions to clinicians in useful ways, and getting clinicians engaged in the process. Open challenges and the role of regulation in this area are briefly discussed. Although these techniques have enormous potential to improve care and personalize recommendations for individuals, the hype regarding them is tremendous. Organizations will need to approach this domain carefully with knowledgeable partners to obtain the hoped-for benefits and avoid failures.
A single-arm multicenter phase II trial of doxorubicin (Doxo) in combination with trabectedin (Trab) given as first-line treatment to patients with metastatic/advanced uterine (U-LMS) and soft tissue leiomyosarcoma (ST-LMS): Final results of the LMS-02 study.
Authors: Patricia Pautier, Anne Floquet, Christine Chevreau, Nicolas Penel, Cecile Guillemet, Corinne Delcambre, Didier Cupissol, Frederic Selle, Nicolas Isambert, Sophie Piperno-Neumann, Esma Saada-Bouzid, Francois Bertucci, Emmanuelle Bompas, Pascaline Boudou-Rouquette, Olivier Collard, Valérie Le Brun Ly, Maud Toulmonde, Axel Le Cesne, Benjamin Lacas, Florence Duffaud
Journal: Journal of Clinical Oncology (2020)

11506 Background: U-LMS and ST-LMS are rare tumors with poor prognosis when locally advanced or metastatic, and with moderate chemosensitivity. Overall response rates (ORR) given in the 1 st -line setting do not exceed 50% for U-LMS and 35% for ST-LMS with a mean response duration of 3- 6 months without impact on overall survival (OS). In 2015 we reported very encouraging results of the LMS-02 study (NCT02131480) with ORR of 59.6% in U-LMS, and 39.3% in ST-LMS with manageable toxicity (Pautier; Lancet oncol 2015). Herein, we report the updated results of progression-free survival (PFS) and final results of overall survival (OS). Methods: Patients (pts) received 60 mg/m² intravenous Doxo followed by trabectedin 1.1 mg/m 2 as a 3-hour infusion on Day 1 and pegfilgrastim on Day 2, repeated every 3 weeks for up to 6 cycles. Surgery for residual disease was permitted. Patients were stratified into U-LMS and ST-LMS groups. Results: Overall, 108 patients with LMS with a median age of 59 years and mostly metastatic disease (85%) were enrolled. Of those, 77 patients (71.3%) have received all 6 cycles of treatment, and 20 patients (18.5%) had metastasis resection. With a median follow-up of 7.2 years (95% CI: 6.9 - 8.2), the overall median PFS was 10.1 months (95% CI: 8.5 - 12.6), being 8.3 months (95 CI: 7.4 - 10.3) and 12.9 months (95% CI: 9.2 - 14.1) in U and ST group, respectively. Median OS was 34.4 months (95% CI: 26.9 - 42.7), being 27.5 months (95% CI: 17.9 - 38.2) in U-LMS and 38.7 months (95% CI: 31.0 - 52.9) in ST-LMS group. The median OS among the 20 pts with surgery was not reached vs 31.6 months in the population without surgery (95% IC: 23.9 - 35.4). Conclusions: The Doxo +Trab combination is an effective 1st-line therapy for pts with LMS, with promising PFS and OS results and an acceptable safety profile. Merely for comparison, the most recent results of Doxo alone in metastatic LMS, given in 1st-line setting in a phase III ANNOUNCE trial conducted during the same period, reported median PFS of 6.9 months, and median OS of 21.9 months (ASCO 2019 LBA3). Results of the LMS04 trial (NCT02997358), a randomized phase III study comparing this combination vs Doxo alone in 1st-line therapy in metastatic LMS are pending. Clinical trial information: NCT02131480 .