tbuckley/cabot-search huggingface dataset:
DAROL: DARolutamide ObservationaL study patients in nonmetastatic castration-resistant prostate cancer (nmCRPC) patients.
Authors: Evan Y. Yu, Christopher Michael Pieczonka, Alberto Briganti, Declan G. Murphy, Thierry Lebret, Murilo Luz, Hiroyoshi Suzuki, Antoine Thiery-Vuillemin, Jorge A. Ortiz, Rongjin Guan, Andrew J. Armstrong
Journal: Journal of Clinical Oncology (2020)

TPS5593 Background: Patients (pts) with prostate cancer treated with prolonged androgen deprivation therapy (ADT) will eventually develop castration-resistant disease. Treatment of pts with nmCRPC with darolutamide (DARO) delays the development of metastases, which are associated with cancer-related morbidity. DARO is a structurally unique oral androgen receptor inhibitor approved by the FDA for the treatment of nmCRPC, based on prolonged metastasis-free survival (MFS) compared with placebo (median 40.4 months vs.18.4 months, respectively) in the ARAMIS phase III clinical trial. DARO showed a similar incidence of adverse events (AEs) compared to ADT alone and has a low potential for drug-drug interactions. However, phase III clinical trials cannot fully reflect all the facets of real-world pts. Therefore, non-interventional studies in the real-world setting, such as DAROL, are able to provide additional insight into the patterns of use and real-world safety profile of recently approved drugs. Methods: (NCT04122976) will enrol participants in the US, Brazil, Japan, and the EU. Eligible pts include men with histologically confirmed nmCRPC aged ≥18 yrs, life expectancy ≥3 months, and initiated on DARO treatment as per investigators’ decision within 3 days prior to enrollment. DAROL opened for enrollment in December 2019 in the US with a projected enrollment of 1000 pts. The primary endpoint of DAROL is safety. Treatment-emergent AEs will be collected during the study. Secondary endpoints to measure clinical effectiveness are MFS, time to symptomatic skeletal event, time to prostate-specific antigen progression, survival rate, and duration of DARO therapy. Other endpoints include pt demographics and characteristics, and prior and subsequent therapy. The estimated primary completion date is December 30, 2024. Clinical trial information: NCT04122976 .
Clinicians should not restrict access to basic information
Authors: A. Maynard, T. Sheldon
Journal: BMJ (1995)

EDITOR,—The articles on the rise of Stalinism in the NHS, which espouse liberty to facilitate transparency and accountability so that clinicians and others can blow the whistle on poor management practices, are laudable.1 However, consistency in advocacy and behaviour is essential.

Openness for whistle blowers should facilitate public analysis …
A survey on requirement of job training for community physicians in Hedong Distract of Tianjin
Authors: Wei-yun Chen, Yun Wang, Xiao-hui Zhang
Journal: BMJ (2010)

A questionnaire survey was conducted in 120 community physician, the survey items included the methods and contents of training course, the obstacles for attendance of training; meanwhile, focus group discussions attended by selected physicians were also carried out The skills for diagnosis and treatment of common diseases were most required by community physicians, and disease prevention and rehabilitation were ranked second and third respectively. In addition, the physicians also required the knowledge and skills of pre-hospital emergency management, disease screening and chronic disease management. The most favorable way of training is in-site guidance given by doctors from higher level hospital. Staff shortage in community health service centers is the main obstacle for off-service training.

Key words: 
lnservice training;  General practitioners
Incidence and risk factors for pneumonitis associated with immune checkpoint inhibitors in advanced-stage non-small cell lung cancer: A single center experience.
Authors: Felipe Soto, Linda Zhong, Vickie R Shannon, Nathaniel Wilson, Abdulrazzak Zarifa, Fechukwu Akhmedzhanov, John Heymach, Muhammad H Arain, Jeff Lewis, Waree Rinsurongkawong, J. Jack Lee, Jianjun Zhang, Stephen Swisher, Tito R. Mendoza, Aung Naing, Ajay Sheshadri, Mehmet Altan
Journal: Journal of Clinical Oncology (2020)

e15089 Background: Conventional treatments for advanced-stage non-small cell lung cancer (NSCLC) confer a progression-free survival of only about 6 months. Immune checkpoint inhibitors (ICIs) have become standard therapies in the management of advanced NSCLC, but are associated with a variety of immune-related adverse events that may be dose-limiting (irAEs). Risk factors for ICI-related pneumonitis, a potentially fatal irAE, have not been well established. We sought to determine the incidence and risk factors for ICI-related pneumonitis in NSCLC in a cohort of patients treated with ICIs as standard of care or as part of a clinical trial. Methods: We performed a retrospective review of 525 patients with advanced NSCLC who received ICI therapy with PD-1 inhibitors, with or without CTLA-4 inhibitors, at MD Anderson Cancer Center between 2015 and 2018. Patients with incomplete data were excluded from the study. Clinical data was collected at the time of ICI therapy and at the time of irAE. The diagnosis of pneumonitis was based on clinical presentation, imaging findings, and microbiological results. We constructed a Fine-Gray competing risks regression model with pneumonitis as the outcome of interest and all-cause mortality as the competing risk. Results: In our initial data analysis based on available data shows a 9.7% raw incidence of pneumonitis (17/177). We found no association between age, race, gender, type of anti-PD-1 therapy, concurrent use of CTLA-4 inhibitors, tumor histology, cumulative radiation dose, or smoking pack-years with the risk for pneumonitis. Patients who were therapy-naïve at the initiation of ICI therapy (hazard ratio [HR] 3.3, 95% confidence interval [CI] 1.0-10.6, p = 0.04), and patients with prior lung disease (HR 2.7, 95% CI 0.8-8.5, p = 0.1) had around a three-fold increase in the risk for pneumonitis after accounting for the competing risk of mortality. Conclusions: NSCLC patients who are therapy-naïve or have prior lung disease on initiation of ICI therapy have a higher risk for pneumonitis. Other studies have shown an increase in pneumonitis in therapy-naïve patients, but the association with prior lung disease is novel. Further analysis on this cohort is ongoing.
精神分裂症的临床识别与社区康复管理
Authors: 李文咏
Journal: BMJ (2009)

重性精神疾病是指精神活动严重受损,导致对自身健康状况或者客观现实不能完整辨认,或者不能控制自身行为的精神疾病.其中精神分裂症是最主要的疾病之一.精神分裂症是指一组病因未明的精神病,多起病于青壮年,常有感知、思维、情感、行为等方面的障碍和精神活动的不协调.一般无意识障碍和智力缺损,病程多迁延[1]393。
Factors associated with low chemotherapy dosing in high risk breast cancer.
Authors: Leilani Hernandez, Nicole Fergestrom, John A. Charlson, Joan Marie Neuner
Journal: Journal of Clinical Oncology (2020)

e15520 Background: Chemotherapy dose is often reduced or delayed due to adverse effects. However, a low relative dose intensity (RDI) is associated with reduced disease control and survival. There is little data among patients receiving modern breast cancer regimens regarding the risk of low RDI, or factors associated with it. Methods: We used an institutional registry at a large multidisciplinary cancer center to identify subjects with incident invasive, non-metastatic breast cancer diagnosed between 2009-2018. We focused on a subset of high-risk patients for whom chemotherapy is clearly recommended by guidelines: triple negative (estrogen receptor, progesterone receptor and HER2 negative) or HER2-positive subtypes, and either positive lymph node metastases or tumor size &gt; 1.0 cm. We obtained administration dates and doses for the following agents: doxorubicin, cyclophosphamide, paclitaxel, docetaxel, and carboplatin. Our primary outcome was RDI &lt; 85% of guideline-recommended doses of at least one of these agents. Other outcomes included dose of each agent (first cycle dose &lt; 85% or total dose &lt; 85) and timing (delay ≥7 days or early discontinuation). Variables used for analyses included BMI ≥25, race, HER2 status, age ≥55 years, marital status, stage, and Charlson co-morbidity score. Results: More than half of our cohort of high risk breast cancer patients experienced a low RDI of at least one chemotherapy agent. Out of the 237 patients who met our inclusion criteria, 60% had a low RDI, 10% received a low first cycle dose, 38% received a low total dose, and 46% experienced either a dose delay or discontinued treatment. Using logistic regression analyses, we found that being overweight (CI: 1.01-3.54; p = 0.046) and stage 3 breast cancer (CI:1.05-5.96; p = 0.038) were associated with increased odds of having a low RDI. Low total dose was associated with being overweight (p = 0.0181), unmarried (p = 0.0278), and stage 3 (p = 0.0201). HER2-positive status was also associated with a low first cycle dose (p = 0.001) and dose delays or discontinuation (p = 0.0002). Conclusions: Having a BMI ≥25, higher-stage, or being unmarried, which may serve as a proxy for low social support, are factors that may help identify patients who will have guideline-recommended chemotherapy doses reduced.
Safety and tolerance of androgen receptor antagonists in nonmetastatic, castration-resistant prostate cancer.
Authors: Sariya Wongsaengsak, Nusrat Jahan, Fred L. Hardwicke
Journal: Journal of Clinical Oncology (2020)

e17607 Background: Metastatic castration resistant prostate cancer (mCRPC) is a fatal disease. Nonmetastatic, castration-resistant prostate cancer (nmCRPC) often predates mCRPC. Recently, three androgen receptor (AR) antagonists i.e. apalutamide, enzalutamide, and darolutamide have been approved for nmCRPC. Nonetheless, any new therapeutic approach poses new safety concerns. We conducted a systematic review and meta-analysis of the published phase 3 randomized controlled trials (RCTs) to determine the safety and tolerance of AR-antagonists in nmCRPC patients. Methods: We conducted a systematic search at PUBMED, MEDLINE, EMBASE, and meeting abstracts as per PRISMA guidelines from inception until November 2019. Published phase 3 RCTs using AR-antagonists in the study arm for nmCRPC were included in the analyses. We used Mantel-Haenszel (MH) method and random effects model to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was tested with I2 value and Cochran’s Q-test. Results: Three phase 3 RCTs (ARAMIS, PROSPER, and SPARTAN) comprising 2687 patients in the AR-antagonist arm and 1417 patients in the control arm were included in the final analysis. AR-antagonists used in the study arms were following— ARAMIS: darolutamide, PROSPER: enzalutamide, and SPARTAN: apalutamide. Placebo was used in the control arms. All patients continued androgen deprivation therapy (ADT). Randomization was 2:1 in all studies. No publication bias was appreciated all three studies. The pooled RR of any-grade adverse events (AEs) is 1.08 (95% CI: 1.02 – 1.14, p = 0.01, I 2 = 79%) which was statistically significant. The pooled RR of grade ≥ 3 AEs was also significant at 1.32 (95% CI: 1.19 – 1.46, p &lt; 0.00001, I 2 = 0%). The pooled RR of grade 5 event is 2.67 (95% CI: 0.79 – 9.02, p = 0.11, I 2 = 70%) which was not statistically significant. The pooled RR for discontinuation of treatment regimen was also statistically significant at 1.31 (95% CI: 1.00 – 1.72, p = 0.05, I 2 = 35%). Conclusions: In nmCRPC patients, AR-antagonists in combination with ADT is associated with a mild increase risk of any-grade AEs, grade ≥3 AEs, and treatment discontinuation secondary AEs. However, AR-antagonists were not associated with a significantly increased risk of death due to AEs. Careful clinical vigilance and timely intervention with appropriate supportive care are critical to prevent AEs related morbidities and prevent treatment discontinuation.
Quality of life and its affecting factors for elderly residents at Shimenerlu community of Shanghai
Authors: Yu-miao Wu
Journal: BMJ (2009)

In order to evaluate the quality of life and affecting risk factors for the elderly populations, cluster sampling method was used to investigate 1731 elderly individuals at Shimenerlu Community in Shanghai. The results showed that the average quality of life of the participants was above medium level, and most elderly demonstrated good quality of life. Moreover, 1536 elderly individuals (88.9%) developed at least one chronic disease, and the incidence of depression was up to 17. 2%. Affecting factors of quality of life included daily life capability, severity of disease, age, depression symptom, marriage, community activities, care provider, gender, number of disease, diabetes, hobby, income, expense, family support, and living conditions. No correlation with education, career, health insurance, and partner's disease was found. Those data suggest that community heahhcare should pay more attention to the management of chronic diseases and mental health, the development of family resources, and the improvement of hobbies and social activities in the elderly populations.

Key words: 
Quality of life; Elderly
The relationship between tumor-infiltrating lymphocytes, PD-L1 expression, and clinical outcomes of Asian melanoma patients treated with anti-PD-1 antibody.
Authors: Soo Jung Lee, Yee Soo Chae, Jong Gwang Kim, Byung Woog Kang, Jin Ho Baek, Hyeokjin Choi, In Hee Lee, Ji Yun Jeong
Journal: Journal of Clinical Oncology (2020)

e22010 Background: Clinical feature of Asian melanoma patients are distinct from those of Western patients. Acral and mucosal melanomas, which are common in Asian populations, predominantly occur in sun-protected areas. Immune-checkpoint inhibitors are standard treatment for inoperable melanoma, however, they are less effective against acral and mucosal melanomas. The aim of our study is to investigate the expression, clinical significance and association of programmed death-ligand 1 (PD-L1) with tumor-infiltrating lymphocytes (TIL) in Asian melanoma patient treated with anti-PD-1 therapy. Methods: Patients with unresectable stage III or metastatic stage IV melanoma who began anti-PD-1 antibody therapy between February 2016 and September 2018 were enrolled. Immunohistochemistry was used to evaluate PD-L1 expression and stromal CD8+ TIL, and PD-1+ TIL densities within the intratumoral regions and associated stromal regions. Baseline characteristics and blood parameters including neutrophil to lymphocyte ratio (NLR) were assessed, and outcome and adverse events were evaluated according to subtypes. Results: Of the 57 cases, the most common type was acral melanoma (n = 28, 49.1%) followed by mucosal melanoma (n = 19, 33.3%) and cutaneous (n = 10, 17.5%). The overall response was 8.8 % and disease control rate was 33.3%. The median progression-free survival (PFS) was 18.0 months (95% confidence interval, 12.57 to 23.43), and there was no difference in PFS according to subtypes. Overall, 29.8% (n = 17) showed PD-L1 expression in tumor cells and 26.3% in immune cells. PD-L1, CD8+TIL, LDH and BRAF V600 statues were not associated with response or survival. NLR (≥ 5) were independent poor prognostic factors by multivariate analysis. Conclusions: In our study, anti-PD-1 therapy showed less effective compared to western patients. High NLR (≥ 5) could predict response of anti-PD-1 therapy in patients with Asian melanoma. Considering the differences in genetic backgrounds and therapeutic efficacy of immunotherapy, specialized therapeutic strategies for Asian melanoma should be established.
Complications in patients surviving over ten years after liver transplantation
Authors: Xinyu Li, Lei Huang, Jiye Zhu
Journal: BMJ (2019)

Objective
To analyze the complicationsin patients surviving over ten years after liver transplantation.


Methods
Total 397 patients underwent liver transplantation from May 2000 to May 2008 at Department of Hepatobiliary Surgery, Peking University People′s Hospital, among whom 217 patients survived for ≥10years; after 12 cases with incomplete data were excluded, 205 cases were enrolled in the study. The complications of patients after liver transplantation were analyzed.


Results
The survival rate of patients over 10 years after liver transplantation was 51.6% (205/397). In 205 patients surviving ≥10years after liver transplantation, the incidence of de novo neoplasms was 3.9% (n=8); the prevalence of hyperuricemia,obesity,hyperlipidemia, metabolic syndrome, hypertension, and diabetes was 54.1% (n=111), 52.2% (n=107), 48.3% (n=99), 46.8% (n=96), 42.9% (n=88), and 18.5% (n=38), respectively. The recurrence rate of hepatitis B and the incidence of newly infected hepatitis B were 2.0% (n=4) and 1.0% (n=2), respectively. The incidence of cardiovascular and cerebrovascular events, renal insufficiency and biliary complications were 2.0% (n=4), 4.9% (n=10) and 12.2% (n=25), respectively. Fourteen patients dies 10 years after liver transplantation, the causes of death were cancer (n=4), biliary complications (n=4), recurrence of hepatitis B (n=2), cardio-cerebrovascular disease (n=2), renal insufficiency (n=1), and secondary liver transplantation (n=1).


Conclusion
Liver transplantation may prolong survival of patients with terminal liver diseases. The neoplasms, metabolic diseases, cardiovascular and cerebrovascular diseases, hepatitis B recurrence and chronic renal damage would affect the long-term survival of patients after liver transplantation.


Key words: 
Liver transplantation; End stage liver disease; Survival analysis
Success and failure of additional immunosuppressants in steroid-refractory pneumonitis related to immune checkpoint blockade.
Authors: Jason Beattie, Paige Fuentes, Hira Rizvi, Jia Luo, Adam Jacob Schoenfeld, Michael A. Postow, Margaret K. Callahan, Allison Betof Warner, Mohit Chawla, Matthew David Hellmann
Journal: Journal of Clinical Oncology (2020)

3078 Background: Severe immune related adverse events (irAEs) with immune checkpoint blockade are uncommon but can be fatal. Steroids are the most common initial treatment for most non-endocrine irAEs, but some patients are or become refractory to steroids. When steroids are not effective, there is limited data to guide management strategies, particularly in the context of pneumonitis. Methods: All patients at MSK treated with immune checkpoint blockade from 2013-2020 were queried for receipt of an immunosuppressant (e.g. TNF antagonists, mycophenolate mofetil, cyclophosphamide) beyond steroids. Patient records were then manually reviewed to identify patients who received such therapy for management of immunotherapy-related pneumonitis. Results: Among 5363 patients treated with immune checkpoint blockade, 364 (6.8%) received an additional immunosuppressant for an irAE, including 28 (0.5% of all patients treated) patients treated for pneumonitis. Most of these pneumonitis events (19/28, 68%) were grade 3 or higher. Agents used included mycophenolate mofetil (7/28; 25%), TNF antagonists (23/28; 82%), and cyclophosphamide (1/28; 3.5%); more than one medication was used in 3 patients (11%). The indications were primary non-response to steroids (n = 16, 57%) and recrudescence after initial response to steroids (n = 12, 43%). At 90 days from initiation of the additional immunosuppressant, 13/28 (46%) patients were alive with improvement or resolution of pneumonitis while 15/28 (54%) had died. Survival with resolution/improvement was more common in patients treated for recrudescence vs primary non-response (67% vs 25%, p = 0.05). Conclusions: Outcomes with additional immunosuppressants in the setting of steroid-refractory immune-related pneumonitis are poor, but resolution can occur in some cases. A deeper understanding of the mechanistic underpinnings of irAEs is needed to more effectively tailor immunosuppressant therapies, particularly in severe pneumonitis events.
Preliminary safety and pharmacodynamic (PD) activity of XmAb20717, a PD-1 x CTLA-4 bispecific antibody, in a phase I dose escalation study of patients with selected advanced solid tumors.
Authors: Barbara Hickingbottom, Raphael Clynes, John Desjarlais, Caiyan Li, Ying Ding
Journal: Journal of Clinical Oncology (2020)

e15001 Background: Interim safety and PD data from an ongoing first-in-human, multi-center, open-label dose escalation study of XmAb20717 (XmAb20717-01; NCT03517488) are reported here. The primary objectives were to determine safety, tolerability, and the MTD and/or recommended doses (RDs). Secondary objectives included preliminary anti-tumor activity and PK/PD. Methods: A 3+3 dose escalation design was used to establish an MTD/RD(s) for infusions on Days 1 and 15 of each 28-day cycle. DLT evaluation was based on Cycle 1 through Day 28. Patients with selected solid tumors (in indications both with and without approved checkpoint therapy) who have exhausted standard of care are eligible. Results: As of 05FEB 2020, 34 patients were treated in cohorts 1-6 at fixed doses of 0.15 to 10 mg/kg. Patients had a median age of 57 years (range 32-81), a median time since initial diagnosis of 42 months (range 3 -313), and a median of 4 prior systemic therapies (range 0-9). 68% of patients had a TNM stage of III/IV, and 68% had been exposed to checkpoint therapy. XmAb20717 treatment was generally well tolerated through the highest dose cohort tested. Overall rates of Gr3/4 immune-related AEs occurred in 8 (24%) patients including elevations of transaminases 3 (9%), rash 2 (6%), lipase and amylase 1 (3%, without clinical symptoms or radiographic evidence of pancreatitis), lipase (alone) 1 (3%), pruritus 1 (3%), hyperglycaemia 1 (3%), arthritis 1 (3%) and colitis 1 (3%), all reversible. Responses were evaluated based on RECIST 1.1 criteria, and there was 1 CR reported (melanoma, progressed on prior pembrolizumab) at 10 mg/kg (highest dose level). Dose-dependent pharmacodynamic activity consistent with dual PD-1/CTLA-4 blockade was noted, namely a proliferative burst of both CD8 and CD4 T cells and induction of IFN-inducible chemokines (Table). Conclusions: XmAb20717 is generally safe and has demonstrated PD activity in heavily pretreated patients with selected advanced solid tumors. Dose escalation continues. Clinical trial information: NCT03517488 . [Table: see text]
Phase II study of biweekly docetaxel plus androgen-deprivation therapy (ADT) in patients with previously-untreated, metastatic, prostatic adenocarcinoma.
Authors: Seonggyu Byeon, Hana Kim, Hongsik Kim, Hwang Gyun Jeon, Seong Soo Jeon, Hyun Moo Lee, Se Hoon Park
Journal: Journal of Clinical Oncology (2020)

e17580 Background: To evaluate the efficacy and safety of biweekly docetaxel (bD) plus androgen-deprivation therapy (ADT) in metastatic castration-naïve prostate cancer (mCNPC). Methods: This was an open-label, prospective, single-arm phase II trial. 42 patients with mCNPC were treated with docetaxel 40 mg/m 2 every two weeks plus ADT. The primary end point was one year castration-resistant prostate cancer (CRPC)-free survival rate and the secondary end points were prostate-specific antigen (PSA) response, time to CRPC and safety. Results: Most patients (87.5%) had Gleason score 8 or more. The median value of PSA at initial treatment was 66.9 ng/ml (range 0.04 to 2339). After bD plus ADT, 39 patients (92.9%) had a PSA response (reduced PSA level 50% or more). The time to CRPC (one-year CRPC free survival 73.6%) and the duration of PSA response (18 months response 80.4%) did not reach the median. The bD plus ADT regimen was well-tolerated. The most common adverse events included neutropenia, nail changes and diarrhea. Conclusions: bD plus ADT treatment demonstrated favorable treatment outcomes with tolerability. Clinical trial information: NCT03061643 .