tbuckley/cabot-search huggingface dataset:
Role of tafamidis in reducing the effect and progression of transthyretin amyloid cardiomyopathy.
Authors: Raghunandan Konda, David Vadala, Abdul Rafae, Sakiru Isa, Vishal Devarkonda, Kavitha Kesari, Arvind Kunadi
Journal: Journal of Clinical Oncology (2020)

e15612 Background: Transthyretin Amyloid Cardiomyopathy (ATTR-CM) is a rare, life-threatening, progressive and underdiagnosed cause of restrictive cardiomyopathy and heart failure. ATTR-CM is a type of cardiac amyloidosis caused due to misfolded and destabilized transthyretin amyloid protein deposits in the myocardium. Tafamidis is a transthyretin (TTR) modifying targeted drug that stabilizes and prevents tetramer dissociation and amyloid deposits. Our aim is to conduct a review of literature to determine the effect of tafamidis on the structural progression of transthyretin cardiomyopathy while also looking into all-cause mortality outcomes. Methods: A systematic search was performed in PubMed, Embase, and Cochrane using the MESH terms "Tafamidis" and “Transthyretin Amyloid cardiomyopathy.” Two authors independently reviewed article titles and abstracts. Disagreements were resolved by consensus and then adjudicated by a third author. All articles published in English up to the year 2019 were eligible for inclusion. Data was tabulated and analyzed. Studies measuring mortality outcomes and echocardiogram findings with the use tafamidis in ATTR-CM were included. Studies that did not measure mortality outcomes were excluded as well as case reports and animal studies. Results: Out of the studies identified through databases (n = 57), only 6 studies met the inclusion criteria as earlier studies delved strictly into the tolerability and safety of the drug. The studies that were included in this analysis are heterogeneous, because ATTR-CM is phenotypically heterogeneous (wild type-ATTR-CM or mutant ATTR-CM) and has varying degrees of amyloid deposits and cardiac symptoms. The role of tafamidis in reducing the effect of cardiomyopathy in transthyretin amyloid cardiomyopathy is unclear. Effects on the structural changes of the myocardium including the ejection fraction remain inconsistent. A recent multicenter, international, phase 3 randomized controlled trial shows reduction in all-cause mortality comparing tafamidis vs placebo. (29.5% vs 42.9%). Conclusions: With the recent approval of tafamidis, it is vital to review and analyze the available data to study its effects on transthyretin amyloid cardiomyopathy. While structural improvements with tafamidis therapy are inconsistent, reduction in all-cause mortality with this novel drug is promising.
Research advances in diagnosis and treatment of duodenal varices
Authors: Wenming Wu, Xiaofeng Liu
Journal: BMJ (2017)

Duodenal varices are an uncommon disease which occurs along the entire gastrointestinal tract outside the esophagus or stomach. Among ectopic varices, duodenal varices are the most common one. Cirrhosis, hepatic portal hypertension, extrahepatic portal vein occlusion and vasculitis contribute to the pathogenesis of ectopic variceal formation. The unusual pathophysiology, location, diversity and uncertain curative effect of DV are associated with its low detection rate and high mortality of patients. Therefore, the diagnosis and treatment of DV is one of the tough problems in clinical practice. This article reviews the current research advances in pathophysiology, diagnosis and treatment of duodenal varices to provide reference for clinical practice.


Key words: 
Varicose veins; Duodenum; Diagnosis
Stem cell transplant and financial toxicity: A single-center prospective cohort analysis.
Authors: Syed Hussaini, Yi Ren, Meagan Lew, Lauren Bohannon, Jillian C Thompson, Yousuf Zafar, Anthony Derek Sung
Journal: Journal of Clinical Oncology (2020)

e19373 Background: Increasing healthcare costs often result in many individuals and families foregoing required care, delaying care, or non-adhering to prescribed medication. Hematopoietic cell transplantation (HCT) is a highly specialized procedure that has the potential to adversely affect the socioeconomic well-being of patients and their family. Financial well-being in patients undergoing evaluation for HCT has been inadequately studied. In this prospective cohort study, we examined financial toxicity in a cohort of patients being considered for HCT at the Duke Adult Bone Marrow Transplant Clinic. Methods: This is a prospective cohort review of patients age ≥18 years undergoing evaluation for allogeneic HCT between 1/1/2017 – 1/1/2020. Patients that completed a baseline financial health survey and the comprehensive score for financial toxicity-functional assessment of chronic illness therapy (COST-FACIT) survey were included. Financial health was measured via baseline survey and financial distress was assessed via the validated COST-FACIT measure. The primary outcome was financial distress. Results: Of 157 consecutive patients, 112 (71.3%) completed financial toxicity assessments. Of these, 63.4% were male, had a mean age of 61.0, were predominantly white (74.4%), and majority had household incomes less than $90,000 (53.7%). Primary diagnosis at screening was leukemia (35.4%) and myelodysplastic neoplasm (31.7%). Overall, 94.5% noted an inability to see a physician in the prior year due to cost, 76.8% had not filled a prescription due to cost, 73.2% reduced spending on basics like food or clothing to pay for cancer care, 69.5% borrowed money or used a credit card to pay for cancer care, 54.9% used all or a portion of their savings to pay for cancer care, and 54.9% reduced spending on leisure activities like vacations, eating out, or movies to pay for cancer care. Overall, 31 (37.8%) respondents noted mild financial distress while 26 (34.1%) noted moderate-to-high financial distress. Conclusions: Previous studies in the solid tumor and hematological malignancy fields have noted similar results in financial toxicity. However, this is the first study of its kind to demonstrate prevalent financial toxicity present in a cohort of patients undergoing evaluation for HCT. Early interventions by physician and social work led teams may benefit patients who are at risk for financial distress. Future directions include investigating factors associated with high financial toxicity in HCT, and whether financial distress is related to worse outcomes after transplant.
Evaluation of the Cost-effectiveness of Services for Schizophrenia in the UK Across the Entire Care Pathway in a Single Whole-Disease Model
Authors: Huajie Jin, Paul Tappenden, James H. MacCabe, Stewart Robinson, Sarah Byford
Journal: JAMA Network Open (2020)

The existing economic models for schizophrenia often have 3 limitations; namely, they do not cover nonpharmacologic interventions, they report inconsistent conclusions for antipsychotics, and they have poor methodologic quality.To develop a whole-disease model for schizophrenia and use it to inform resource allocation decisions across the entire care pathway for schizophrenia in the UK.This decision analytical model used a whole-disease model to simulate the entire disease and treatment pathway among a simulated cohort of 200 000 individuals at clinical high risk of psychoses or with a diagnosis of psychosis or schizophrenia being treated in primary, secondary, and tertiary care in the UK. Data were collected March 2016 to December 2018 and analyzed December 2018 to April 2019.The whole-disease model used discrete event simulation; its structure and input data were informed by published literature and expert opinion. Analyses were conducted from the perspective of the National Health Service and Personal Social Services over a lifetime horizon. Key interventions assessed included cognitive behavioral therapy, antipsychotic medication, family intervention, inpatient care, and crisis resolution and home treatment team.Life-time costs and quality-adjusted life-years.In the simulated cohort of 200 000 individuals (mean [SD] age, 23.5 [5.1] years; 120 800 [60.4%] men), 66 400 (33.2%) were not at risk of psychosis, 69 800 (34.9%) were at clinical high risk of psychosis, and 63 800 (31.9%) had psychosis. The results of the whole-disease model suggest the following interventions are likely to be cost-effective at a willingness-to-pay threshold of £20 000 ($25 552) per quality-adjusted life-year: practice as usual plus cognitive behavioral therapy for individuals at clinical high risk of psychosis (probability vs practice as usual alone, 0.96); a mix of hospital admission and crisis resolution and home treatment team for individuals with acute psychosis (probability vs hospital admission alone, 0.99); amisulpride (probability vs all other antipsychotics, 0.39), risperidone (probability vs all other antipsychotics, 0.30), or olanzapine (probability vs all other antipsychotics, 0.17) combined with family intervention for individuals with first-episode psychosis (probability vs family intervention or medication alone, 0.58); and clozapine for individuals with treatment-resistant schizophrenia (probability vs other medications, 0.81).The results of this study suggest that the current schizophrenia service configuration is not optimal. Cost savings and/or additional quality-adjusted life-years may be gained by replacing current interventions with more cost-effective interventions.
Association of molecular subtypes with pathologic response in a phase II study of co-expression extrapolation (COXEN) with neoadjuvant chemotherapy (NAC) for localized, muscle-invasive bladder cancer (SWOG S1314; NCT02177695).
Authors: Seth P. Lerner, David James McConkey, Catherine Tangen, Joshua J Meeks, Thomas W. Flaig, Xing Hua, Siamak Daneshmand, Ajjai Shivaram Alva, M. Scott Lucia, Dan Theodorescu, Amir Goldkorn, Matthew I. Milowsky, Woonyoung Choi, Richard Carlton Bangs, Daniel Gustafson, Ian Murchie Thompson
Journal: Journal of Clinical Oncology (2020)

5028 Background: Cisplatin-based NAC is recommended for patients with MIBC prior to radical cystectomy (RC) but the majority will not have a pathologic response. To identify responders the COXEN gene expression model with chemotherapy-specific scores (for DD-MVAC and GC) was developed and in a prospective rPII clinical trial (SWOG S1314) the GC score was associated with path downstaging in the pooled arms. We investigated RNA based molecular subtypes as additional predictive biomarkers for response to NAC in patients treated in S1314. Methods: Eligibility required cT2-T4a N0 M0, predominant urothelial, &gt; 5 mm tumor, cisplatin eligible, and plan for RC and PLND. 237 patients were randomized between 4 cycles of ddMVAC and GC. Based on Affymetrix transcriptomic data used to assign COXEN scores, we determined subtypes using 3 classifiers: TCGA (k=5), Consensus (k=6), and MD Anderson (MDA; k=3). Primary objective was to assess subtype association with pathologic response to NAC in the pooled arms and to determine any association with COXEN. TCGA and Consensus classifiers were collapsed into 3 groups for ROC analyses. We tested whether each classifier contributed additional predictive power when added to a model based on pre-defined stratification factors (PS 0 vs. 1; T2 vs. T3, T4a). Results: 161 patients had adequate tissue and gene expression results, received at least 3 of 4 cycles of NAC and had pT-N response based on RC. Covariates were 78% PS=0, 89% T2, 84% male, median age 65, 51% randomized to ddMVAC, 49% GC with 33% pT0 and 52% downstaging. Although the TCGA 3 group classifier (Basal-Squamous (BS)/Neuronal, Luminal, Luminal infiltrated) and GC Coxen score yielded the largest AUCs (0.607, 0.610) for pT0 response, neither reached statistical significance (p=0.20, p=0.22). For downstaging (&lt;pT2), the 3 category Consensus classifier (BS/NE-like, Luminal, Stroma-rich) significantly increased the AUC from 0.568 (strat factors alone) to 0.620 (p=0.044). The MDA classifier AUC was 0.640 and the GC Coxen score AUC was 0.626, but neither were significant (p=0.076, p=0.14. The MVAC Coxen score did not improve the AUC beyond the stratification factors. Conclusions: The Consensus classifier, which is based in part on the TCGA and MDA classifiers, modestly improved prediction for pathologic downstaging when added to clinical stage and PS. With additional followup, we will assess the association of COXEN scores and subtypes with overall survival. Clinical trial information: NCT02177695 .
Biliary stent implantation plus internal or external radiotherapy in malignant obstructive jaundice
Authors: Hai-jiang Wu, Luan Guan, Ning Cui, Chi Cao, Ling Liu, Chao Dong, Yong Luo
Journal: BMJ (2008)

Thirty patients with malignant obstructive jaundice were treated with biliary stent implantation+brachytherapy+conformal radiotherapy (study group; n=15) or biliary stent implantation alone (control group; n=15). Total bilirubin (TBIL) levels significantly declined within 1 month in both groups. However, at 6 months, TBIL values began to increase in the control group and continuously declined in the study group. Maximum tumor diameter increased in the control group, while decreased in the study group (remission rate, 13/15 ). As for the study group, the survival rate at 0. 5, 1, and 2 years was 15/15,14/15, and 10/15, respectively, higher than the control group (15/15,5/15,and 1/15) . Combining biliary stent implantation with brachytherapy and conformal radiotherapy might be a safe and effective treatment of choice for patients with malignant obstructive jaundice.

Key words: 
Jaundice, obstructive;  Stents
A prospective validation cohort study of baseline plasma cell-free DNA (cfDNA) as a prognostic biomarker in newly diagnosed glioblastoma (GBM).
Authors: Stephen Joseph Bagley, Seyed Ali Nabavizadeh, Jacob Till, Aseel Abdalla, Hareena Sanga, Jazmine Mays, Timothy Prior, Andrew Jurgielewicz, Samantha Guiry, Karapet Davtyan, Stephanie S. Yee, Zev A Binder, Donald M. O'Rourke, Steven Brem, Arati Suvas Desai, Erica L. Carpenter
Journal: Journal of Clinical Oncology (2020)

2508 Background: Due to significant interpatient heterogeneity, survival outcomes vary widely in patients with GBM. Novel prognostic biomarkers are needed. We aimed to determine the prognostic impact of baseline plasma cfDNA concentration in patients with GBM. Methods: We analyzed 84 patients with newly diagnosed GBM and at least 7 months of follow-up time. The first 41 patients comprised a previously published derivation cohort (Bagley, Clin Cancer Res 2020). The subsequent 43 patients served as an independent validation cohort. cfDNA was extracted from plasma collected prior to initial surgical resection and quantified by qPCR for a 115 bp amplicon of the human ALU repeat element. Receiver operating characteristic (ROC) curve analysis was used in the derivation cohort to (1) assess the accuracy of plasma cfDNA concentration for predicting progression-free survival status at 7 months (PFS-7), a landmark based on the median PFS for newly diagnosed GBM (Stupp, N Engl J Med 2005), and (2) derive the optimal cutoff for dichotomizing patients into high- and low-cfDNA groups. In the validation cohort, logistic regression was used to measure the association of plasma cfDNA concentration (high vs. low) with PFS-7, adjusted for age, isocitrate dehydrogenase ( IDH) 1/2 mutational status, 0-6-methylguanine-methyltransferase ( MGMT) methylation, extent of resection, and performance status. Multivariate Cox regression was used for overall survival (OS) analysis. Results: In the derivation cohort, the optimal cutoff for plasma cfDNA was 25.0 ng/mL (area under the curve [AUC] = 0.663), with inferior PFS and OS in patients with cfDNA above this cutoff (PFS, median 4.9 vs. 9.5 months, log-rank p = 0.001; OS, median 8.5 vs. 15.5 months, log-rank p = 0.03). In the validation cohort, baseline plasma cfDNA concentration over the cutoff was independently associated with a lower likelihood of being alive and progression-free at 7 months (adjusted OR 0.13, 95% CI 0.02 – 0.75, p = 0.02). OS was also worse in in the validation cohort in patients with high plasma cfDNA (adjusted HR 3.0, 95% CI 1.1 – 8.0, p = 0.03). Conclusions: In patients with newly diagnosed GBM, high baseline plasma cfDNA concentration is associated with worse survival outcomes independent of other prognostic factors. Further validation in a larger, multicenter study is warranted.
躯体化症状和躯体形式障碍
Authors: 施慎逊, 王志阳
Journal: BMJ (2007)

临床上我们经常会碰到这样一类患者:他们因为躯体不适而频繁就诊于综合性医院的各临床科室,但相应的躯体检查和实验室检查结果都无法解释他们的临床表现,医生的无病结论不能令其完全释然,他们常常辗转于就医的途中,疲惫不堪.其实这类患者所患的疾病属于精神科的疾病范畴,即躯体形式障碍(somatoform disorders,SFD).这是一类与心理因素密切相关的,表现为各种躯体症状特殊形式的神经症,临床体格检查和实验室检查均不能发现相应的阳性结果来解释这些躯体症状。
Liquid chromatography coupled to multiple reaction monitoring (LC-MRM) for quantification of PD-L1 and PD1-signaling proteins in non-small cell lung carcinoma (NSCLC).
Authors: Vincent Lacasse, Rene Zahedi, Vincent Richard, Hangjun Wang, Georgia Mitsa, Olivier Poetz, Margaret Redpath, Andreas Papadakis, Mounib Elchebly, Victor Cohen, Jason Scott Agulnik, Gerald Batist, Christopher Borchers, Alan Spatz
Journal: Journal of Clinical Oncology (2020)

e21040 Background: Improving the predictive biomarkers arena of checkpoint inhibitors (CPIs) beyond PD-L1 immunohistochemistry (IHC) is one of the most important unmet need in NSCLC. Up to 50% of patients that show positive PD-L1 expression by IHC do not respond to anti-PD-L1 treatments, and patients with low/undetectable PD-L1 have significantly improved survival with CPI. Moreover, PD-L1 IHC is heterogeneous, can be affected by tissue fixation time and post-translational modifications like glycosylation. Also, multiple studies indicated that PD-L1 expression alone does not reliably reflect the immune status of the tumor, thus requiring the measurement of other members of the PD1 signalling pathway. Methods: To address these issues, we developed a multiplexed targeted mass spectrometry-based (MS) assay for the quantitation of protein members of the PD-1/PD-L1 axis in formalin fixed paraffin-embedded (FFPE) tissue.The effect of fixation time on protein recovery was determined using differentially fixed H1915 cells. Liquid chromatography (LC) coupled to MRM was used to develop a targeted assay for PD-L1, PD-1, PD-L2, NT5E, LCK and ZAP70. Results: After 30 minutes fixation 33.6 µg of protein were extracted per mg of FFPE H1915 cells, while protein recovery after 7 days was 55.8 µg/mg, with greater variability (18% and 28% CV, p-value = ns). The optimized LC-MRM method allows the quantitation of PD-L1 and PD-1 down to 23 amol on-column. We evaluated the utility of our MRM assays using the H1915 FFPE cells (PD-L1 3+ by IHC) and determined an endogenous concentration of PD-L1 and NT5E as being 33.2±0.1 amol/µg of total protein and 4.8±0.5 fmol/µg respectively. Noteworthy, a known glycosylation site of PD-L1 was quantified at 10.9±0.3 amol/µg of total protein (30% of total). As increases sensitivity was required, anti-peptide antibodies were generated against the 15 best peptides. We then evaluated this LC-MRM method using MDA-MB-436 cells with lower levels of PD-L1 protein assessed by IHC. Determination of endogenous PD-L1 concentration (3.0 amol/µg of total protein) was achieved using anti-peptide immuno-enrichment followed by MRM. Conclusions: We developed a fixation time independent extraction technique for FFPE and optimized a highly sensitive LC-MRM method that allows the absolute quantification of our targets. This proteomic workflow allows absolute quantification of the PD-1/PD-L1 axis from FFPE tissue using immuno-enrichment and a multiplexed LC-MRM method.
Current status and training requirement of rural doctors in Hebei Province
Authors: Jinjia Zhang, Min Zhang, Huifang Zhao, Yali Zhang, Yanjie Sun, Xiaoying Xing
Journal: BMJ (2019)

Objective
To survey the current status and training requirement of rural doctors in Hebei province.


Methods
A questionnaire survey was conducted among1 200 rural doctors selected from 11 cities of Hebei province by stratified sampling from October to December 2017. The self-designed questionnaire included general condition, job satisfaction, impact of medical reform policies, training needs of rural doctors.


Results
A total of 1 200 questionnaires were distributed and 1 170 valid ones were retrieved with a recovery rate of 97.5%. Among the 1 170 responders, there were 726 males(62.1%) and 444 females (37.9%); 748 (63.9%) were aged more than 40 years;612 (52.3%) hold secondary school degree; 826 (70.6%) had been working in the village for more than 10 years, and the overall job satisfaction rate was 30.8% (360/1 170). Among all responders, 73.8% (864/1 170) worked in the standardized village clinics, and 72.0% (842/1 170) were contracted with local residents as family doctors; 52.8% (618/1 170) responders believed that the reform policy improved the health care for villagers. In all responders, 98% (1 147/1 170) thought they needed training, 93.6% (1 095/1 170) had received training. The training contents they most needed werethe management of common diseases (904, 77.3%), followed by medical humanities(650, 55.6%) and first aid knowledge (492, 42.1%). The influencing factors for training were lack of time, no energy (656, 54.3%), lack of appropriate training forms (510, 43.6%), economic reasons (476, 40.3%) and so on.


Conclusion
The working status of rural doctors need to befurther improvedand the training need to be strengthened to increase their job satisfaction.


Key words: 
Physicians, primary care; Rural health services; Questionnaire