tbuckley/cabot-search huggingface dataset:
An Alternative Framework for Analyzing Financial Protection in Health
Authors: Jennifer Prah Ruger
Journal: PLoS Medicine (2012)

A greater focus on the role of health systems in health, development, and economic growth has led health policy research and analysis, domestic and global, to scrutinize health financing, insurance, and financial protection. Two World Health Reports (2000 and 2010) [1],[2] have called for evaluating health system performance in terms of health financing, and the World Health Organization's (WHO) 64th World Health Assembly reiterated the need for sustainable health financing and universal coverage worldwide [3]. With this increased focus has come closer examination of conventional frameworks and measures of financial protection in health both from academic [4] and policy [5] circles.

Consensus had developed among academic and policy analysts on two primary metrics, catastrophic and impoverishing spending, for financial protection. Both methods use as a measure the percentage of out-of-pocket health spending in households' overall spending. They differ in the way medical spending is deemed problematic: catastrophic spending is above a threshold percentage, while impoverishing spending pushes a household below the poverty line. Both metrics are helpful indicators of the absolute and relative level of household out-of-pocket health care spending and have been employed in multiple studies worldwide [6]–[10]. Our research group conducted a study focusing on a modification of these metrics—the out-of-pocket spending burden ratio using household equivalent income derived from the Organisation for Economic Co-operation and Development (OECD) Equivalence Scale [11].

But the consensus has given way, and critiques of the conventional approach now run wide and deep. Critics include those who are most invested and who have employed these methodologies [5],[7], and those who argue that estimates of household health expenditures themselves are subject to considerable variability depending on survey design [12]. This article proposes a multidimensional financial protection profile that offers a more holistic view of health spending, one that goes beyond the level of spending to cover aspects directly related to health care, such as health care access and insurance utilization, and examines broader impacts on current and longer-term household consumption. This multidimensional approach aims to help policy makers understand the larger context of household health spending and make health and social policy adjustments to mitigate damaging effects.
Contemporary real-world treatment patterns and outcomes of patients with advanced/metastatic hepatocellular carcinoma receiving second-line systemic therapy in the United States.
Authors: Arjun Gupta, Allicia C Girvan, Kristin M Sheffield, Yongmei Chen, Kelly Rae Kirsch, Elena Gonzalez Gugel, Jessica Peachey, Zhanglin Lin Cui, Mark Yarchoan
Journal: Journal of Clinical Oncology (2021)

279 Background: Several therapies have recently gained regulatory approval in the United States (US) as second-line (2L) treatment options for patients with advanced unresectable or metastatic hepatocellular carcinoma (HCC). Treatment patterns and associated outcomes in a real-world population, especially in the contemporary era, remain understudied. Methods: This retrospective study utilized electronic health record data collected during routine patient care in outpatient oncology practices in the US. Adult patients diagnosed with advanced/ metastatic HCC between April 2017 and January 2020 were identified from the Concerto HealthAI database. Patients who survived at least one month from the end of first-line (1L) systemic therapy but did not initiate 2L therapy were classified as having received supportive care alone (SCA). Demographics, patient and disease characteristics, treatment patterns, and outcomes were described descriptively. Median overall survival (OS) from initiation of 2L therapy or end of 1L therapy for patients receiving SCA until death was estimated by the Kaplan-Meier method. Results: A total of 586 patients with advanced/ metastatic HCC were identified in the database. 330 patients received 1L therapy, and of those patients 63% (N= 207) received systemic 2L therapy (n= 105) or SCA (n= 102). At first diagnosis of advanced/ metastatic HCC, the median age was 64 years, and 86% were male. Of patients with ECOG status available at diagnosis (67%), 45% had ECOG status 0-1. The most common 1L agents prescribed were sorafenib (n= 126, 61%), lenvatinib (n= 28,14%) and sorafenib + nivolumab (n= 13, 6%) The most frequent agents prescribed in 2L were nivolumab (n= 44, 42%), sorafenib (n=18,17%), and lenvatinib (n=9, 9%). The median OS of patients receiving any systemic 2L therapy was 7.7 months (95% confidence interval 5.7-11.1) from time of receiving 2L therapy, whereas the median OS of patients receiving SCA was 5.0 months (95% confidence interval 3.3-7.1) from time of end of 1L therapy. Conclusions: In this contemporary national real-world cohort of patients with advanced/ metastatic HCC, a third of patients who received 1L therapy subsequently received 2L therapy. Next steps include investigating factors associated with non-receipt of 2L therapy, sequencing of therapies when multiple lines of therapies are received, and evaluating outcomes by type of agent received in 2L and beyond.
KEYNOTE-177: Phase III randomized study of pembrolizumab versus chemotherapy for microsatellite instability-high advanced colorectal cancer.
Authors: Kai-Keen Shiu, Thierry Andre, Tae Won Kim, Benny Vittrup Jensen, Lars Henrik Jensen, Cornelis J. A. Punt, Denis Michel Smith, Rocio Garcia-Carbonero, Manuel Benavides, Peter Gibbs, Christelle De La Fouchardiere, Fernando Rivera, Elena Elez, Johanna C. Bendell, Dung T Le, Takayuki Yoshino, Ping Yang, Mohammed Zulfiqar Husain Farooqui, Patricia Marinello, Luis A. Diaz
Journal: Journal of Clinical Oncology (2021)

6 Background: KEYNOTE-177 (NCT02563002) evaluated the antitumor activity of pembrolizumab (pembro) vs chemotherapy ± bevacizumab or cetuximab (chemo) as first-line therapy for patients with microsatellite-instability high/mismatch repair deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC). We present results of the final PFS analysis and analysis of PFS2. Methods: Patients with locally-determined MSI-H/dMMR mCRC and ECOG PS 0 or 1 were randomized 1:1 to first-line pembro 200 mg Q3W for up to 2 years or investigator’s choice of mFOLFOX6 or FOLFIRI Q2W ± bevacizumab or cetuximab (chosen before randomization). Treatment continued until progression, unacceptable toxicity, patient/investigator decision to withdraw, or completion of 35 cycles (pembro only). Patients receiving chemo could crossover to pembro for up to 35 cycles after confirmed PD. Primary end points were PFS (RECIST v1.1, central review) and OS. Secondary end points included ORR (RECIST v1.1, central review) and safety. Exploratory endpoints included duration of response (DOR), PFS2 (time from randomization to progression on next line of therapy or any cause death), and health-related quality of life (HRQoL). Data cutoff was Feb 19, 2020. Results: At data cutoff a total of 307 patients were randomized (153 to pembro, 154 to chemo). Median (range) study follow-up was 32.4 mo (24.0-48.3). Pembro was superior to chemo for PFS (median 16.5 mo vs 8.2 mo; HR 0.60; 95% CI, 0.45-0.80; P= 0.0002). The 12- and 24-mo PFS rates were 55.3% and 48.3% with pembro vs 37.3% and 18.6% with chemo. Confirmed ORR was 43.8% vs 33.1%; median (range) DOR was not reached (2.3+ to 41.4+) with pembro vs 10.6 mo (2.8 to 37.5+) with chemo. PFS2 was longer with pembro vs chemo (median not reached vs 23.5 mo [HR 0.63; 95% CI, 0.45-0.88]). OS analysis is ongoing. Grade ≥3 treatment related adverse event (TRAE) rates were 22% vs 66% for pembro vs chemo. There were no grade 5 TRAEs in the pembro arm and 1 grade 5 intestinal perforation in the chemo arm. HRQoL scores were improved with pembro vs chemo. Conclusions: Pembro provided a statistically significant improvement in PFS vs chemo as first-line therapy for patients with MSI-H/dMMR mCRC, with fewer TRAEs observed. Furthermore, pembro provided a clinically meaningful improvement in PFS2 for patients with MSI-H/dMMR mCRC. Clinical trial information: NCT02563002.
Abstract 10048: Early vs Late Permanent Pacemaker Implantation After Transcatheter Aortic Valve Replacement: A Single Center Experience
Authors: Kinan Kassar, Mark Doyle, Stephen Bailey, Ramzi Khalil
Journal: Circulation (2019)

Introduction: Identification of patients who require permanent pacemaker (PPM) implantation after trans catheter aortic valve replacement (TAVR) prior to hospital discharge is of great clinical imp...
Characterization of undiagnosed pancreatic ductal adenocarcinoma on CT scans.
Authors: John Chang, Madelyn Bartels, Kelsey Beyer, Ashley Maitland, Richard Taft Peterson, Stephen Goldinger, Megan Papesh, Maddapa Kundranda, Phillip Koo, Tomislav Dragovich, Michael A. Choti
Journal: Journal of Clinical Oncology (2021)

380 Background: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths. At present, the best 5-year survival is 25% for resectable PDAC. For small (1 cm) stage 1 PDAC, resection has resulted in much better survival. The goal of this study was to evaluate the appearance and location of early undiagnosed PDAC on computed tomography scans (CT) prior to diagnosis with the goal of minimizing missing early PDAC. We also categorize the errors as either perceptive or cognitive. Methods: PDAC cases were retrospectively reviewed from 1/1/2012 through 12/31/2018 from our tumor registry, identifying 81 cases with paired CT scans both at the time of and prior to diagnosis. Among these, 31 contained imaging features considered diagnostic or suspicious for early PDAC(38%). These “errors” were classified by radiologic features and as well as by location. In addition, errors were classified into “perceptive errors" when the first study was read as normal, and as “cognitive errors” when the report noted an abnormality but failed to note suspicion for malignancy. Results: Among the 31 undiagnosed PDAC, 18 had features of an identifiable mass (58%), 9 had pancreatic ductal dilatation (29%), and 4 had evidence of perivascular soft tissue (13%). 44% of undiagnosed tumors were located in the head-neck, 39% in the body, and 17% in the tail. Perceptive errors were found in 58% and 42% were cognitive. No significant differences were seen between perceptive and cognitive errors based on suspicious features. Conclusions: Radiologic findings of early PDAC was retrospectively evident in more than one third of cases in which prior imaging was performed. These findings are most often masses or ductal dilatation. Location of these undiagnosed tumors were distributed throughout the gland. This study identifies the radiologic features of undiagnosed PDAC which may provide an opportunity for future prospective studies and improved technology which may improve early detection of pancreatic cancer.
Response to ‘pervasive sequence patents cover the entire human genome’
Authors: Shine Tu, Christopher Holman, Adam Mossoff, Ted Sichelman, Michael Risch, Jorge L Conteras, Yaniv Heled, Greg Dolin, Lee Petherbridge
Journal: Genome Medicine (2014)

A response to Pervasive sequence patents cover the entire human genome by J Rosenfeld and C Mason. Genome Med 2013, 5:27. See related Correspondence by Rosenfeld and Mason, http://genomemedicine.com/content/5/3/27 and related letter by Rosenfeld and Mason, http://genomemedicine.com/content/6/2/15
Utilization of liquid biopsy for advanced gastrointesinal malignancies in a community oncology practice.
Authors: Niraj K. Gupta, Crystal Siyu Zhang, Kirpal Singh, Timothy Glass, Nikhil Patel, Murad Aburajab, Mazen Al-Satie, Christopher Crawford, Aneesha Anand, Jianmin Tian, Michael Rowe, Alex Cantafio, Khalid Alkimawi, Kalyan Gorantala, Amanda Swingley, Sonia Puri, Mohamad Yousef, Ala Shiyab, Carolyn Harshberger, Jonathan Saxe
Journal: Journal of Clinical Oncology (2021)

127 Background: Liquid biopsy (LB) offers a non-invasive alternative for obtaining genomic signature of malignancies to develop a tailor-made treatment plan. We evaluated the feasibility and impact on clinical management of liquid biopsies performed on patients with advanced gastrointestinal malignancies in a community setting. Methods: A retrospective chart review of adult patients with stage-IV gastrointestinal malignancies was conducted to gather all the pertinent information, including diagnoses, treatment regimens, results of liquid biopsies and any impact on further management. Results: Data on 42 liquid biopsies performed between Aug 2018 and Mar 2020 was collected. M:F ratio was 1.4: 1. Median age was 57yrs (range 31-86). The diagnoses were; Colo-rectal Ca 22(54.7%), pancreatic 9(21.9%), gastric 2(4.7%), biliary 2(4.7%), HCC 2(4.7%), Appendix 1 (2.3%), CUP 1(2.3%) and others 3(7.1%). One (2.3%) LBs was done before first line treatment and 41(97.7%) were done after the failure of first line treatment. There was insufficient sample in the bx to do tissue-NGS for the pt. who had LB before starting treatments. Majority of LBs, 37(88%) were done after the failure of second line/later treatments compared to 5(12%) done after failing the first line treatment. Patient preference and technical challenge to obtain adequate tissue were the commonest reasons for getting the LBs. Results were available in all (100%) the cases. Median turnaround time was 8 days (range:7-13). The commonest mutations were TP53,APC, KRAS, PIK3CA, BRAF, SMAD4. BRCA-2 was identified in 1 pancreatic ca pt. MSI-H was noted in 3 patients; 2 with Colon ca, and 1 with CUP. An actionable alteration was seen in, 40 (95.2%) of the patients. A FDA approved target-matched drug was available for 27/40(67.5%) pts., if we also consider off-label usage. For those who had an alteration, but no FDA approved target-matched drug was available, 13/40 (32.5%), a clinical trial was available for all 13/13 (100%) of the pts.. 43% of those who had a FDA approved target-matched treatment available, but not approved for their disease, were able to receive the drug off-protocol. Two out of 13(15.3%) of the pts. who had a clinical trial available, were enrolled on a study. Conclusions: Liquid biopsies can be efficiently utilized in a community oncology practice. It offers an attractive option to gather genomic information of malignant cells in patients with advanced GI malignancies to be able to deliver state of the art care to all patients, including those who may not have a convenient access to a tertiary center.
Targeting <i>GNAS</i> mutant appendiceal adenocarcinoma.
Authors: Valsala Haridas, Ichiaki Ito, John Paul Y.C. Shen
Journal: Journal of Clinical Oncology (2021)

470 Background: Appendiceal cancers are rare, comprising just 0.5% of all intestinal neoplasia, preventing the systematic study of these tumors in randomized clinical trials. Given this absence of clinical data, no evidence-based guidelines exist regarding the best management of this disease and no drugs have been developed to specifically target appendiceal adenocarcinoma (AA). The G protein GNAS is the second most frequently mutated gene after KRAS in low-grade (49%) mucinous AA (52%), making it an attractive drug target in this orphan disease. Methods: Using CRISPR, GNAS was knocked out in KM12, SNU175 and SKCO1 gastric cell lines that harbor GNAS R201C mutation. The mutant and KO pairs of cells were evaluated for their proliferation rate and ability to form colonies in a clonogenic assay. RNA sequencing of the mutant and knock out cells was performed to determine pathways potentially associated with the GNAS signaling pathway. The Sanger GDSC was used to identify drugs selectively lethal to GNAS mutant tumors. Results: KM12 cells knocked out for GNAS showed a 40% decrease in proliferation compared to the parent cells with mutant GNAS (p &lt; 0.0001). GNAS knockout significantly reduced colony formation of all three mutant cell lines (KM12: 397 vs. 94, SNU175: 512 vs. 134, and SKCO1: 36 vs. 5, p = 0.0022). Analysis of four GNAS R201C cell lines relative to matched controls identified IGF-1R, MEK and PKC as potential vulnerabilities. In vivo validation experiments are currently ongoing. Conclusions: Our findings suggest preliminarily that GNAS R201C mutant cell lines are oncogene addicted to GNAS growth signal and could be targeted with inhibitor of GNAS or one of its downstream effectors.
Realist synthesis in sport and exercise medicine: ‘time to get real’
Authors: Adam Gledhill, Dale Forsdyke
Journal: British Journal of Sports Medicine (2021)

In sport and exercise medicine (SEM), context is key. By context we mean: ‘What works?’ ‘for whom?’ ‘how?’ and under ‘what circumstances?’ These are four key questions for clinicians who aim to prevent injuries, treat patients and guide return to sport with athletes.

To answer real-world challenges, clinicians will often bow to the Oxford levels of evidence and rely on findings of randomised controlled trials, (RCTs), systematic reviews (SRs) or meta-analyses. These methods are gold standards, recent debate1 notwithstanding. However, in dynamic, changeable and less-controlled sports environments (eg, soccer, rugby) where we strive to achieve optimal performance and health gains, we should challenge our own thinking and traditions to meet the demands of this unique environment.

Recognising a shift to a greater need for implementation science,2 we should consider looking beyond the accepted gold standard. Typically, SRs focus on solely measuring and reporting intervention efficacy,3 they omit implementation context.4 The purpose of this editorial is to promote the value of realist synthesis—as a method that complements clinicians’ use of the traditional levels of evidence.

Realist syntheses …
Frontiers in the treatment of glioblastoma: Past, present and emerging
Authors: Taskeen Iqbal Janjua, Prarthana Rewatkar, Aria Ahmed-Cox, Iqira Saeed, Friederike M. Mansfeld, Ritu Kulshreshtha, Tushar Kumeria, David S. Ziegler, Maria Kavallaris, Roberta Mazzieri, Amirali Popat
Journal: Advanced Drug Delivery Reviews (2021)
SAT0171 Evalution of pulmonary function in patients with osteoporosis
Authors: J Natour, IJ Lombardi, LM Oliveira, AF Mayer, JR Jardim
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> By and large vertebral osteoporotic fractures result, in increased kyphosis angle. This alteration could led to disturbance in the pulmonary function. Spinal deformity is associated with alterations in pulmonary function. <h3>Objectives</h3> Our objective was to evaluate the pulmonary function in osteoporotic patients. <h3>Methods</h3> Fifteen women with osteoporosis and vertebral fracture (G1), 20 women with osteoporosis without vertebral fracture (G2) and 20 mormal women (G3) were selected. All performed spirometry in the Viatrace-130 SL spirometer. <h3>Results</h3> Our results showed that women with osteoporosis and vertebral fracture had increased kyphosis angle (median = 60 degrees), decreased forced vital capacity (G1 vs. G2, p = 0.020; G1 vs. G3, p = 0.039) and forced wxpiratory volume in the first second (FEV1)(G1 vs. G2, p = 0.008; G1 vs. G3, p = 0.014). When compared with women with no vertebral fracture and no osteoporosis there wasn`t difference. There was a negative correlation between thoracic kyphosis and the predicted value of expiratory forced volume in one second (p = 0.003). Since 55 degrees of thoracic kyphosis the pulmonary function had showed compromised (p = 0.021). <h3>Conclusion</h3> We conclude that women with vertebral fracture have an increase of their kyphosis angle and a decrease of pulmonary function.
Sleep disturbances during pregnancy and adverse maternal and fetal outcomes: A systematic review and meta-analysis
Authors: Qingdong Lu, Xiaoyan Zhang, Yunhe Wang, Jinqiao Li, Yingying Xu, Xiaohong Song, Sizhen Su, Ximei Zhu, Michael V. Vitiello, Jie Shi, Yanping Bao, Lin Lu
Journal: Sleep Medicine Reviews (2021)
Comprehensive genomic profiling (CGP) utilizing cell-free DNA (cfDNA) in patients (pts) with pancreatic ductal adenocarcinoma (PDAC).
Authors: Ben George, James Haberberger, Naomi L Ferguson, Ole Gjoerup, Kimberly McGregor, Andrew Eugene Hendifar, Daniel A. Laheru, Colin D. Weekes, Jeffrey S. Ross, Amanda Hemmerich
Journal: Journal of Clinical Oncology (2021)

421 Background: PDAC has a propensity for early systemic dissemination and most pts with primary tumors radiographically confined to the pancreas harbor micro-metastases. cfDNA based CGP offers a non-invasive mechanism to identify actionable genomic targets in PDAC and account for serial clonal evolution in response to therapeutic selection pressure. We interrogated the Foundation Medicine database to characterize cfDNA based CGP in pts with PDAC. Methods: We performed a retrospective analysis of pts with PDAC who underwent cfDNA based CGP between May 2016 and February 2020. cfDNA based CGP was done utilizing either the FoundationOne Liquid (F1-Liquid) or the Foundation-ACT (F-ACT) testing platform. Samples were interrogated for exonic and select intronic regions of cancer-related genes for both F1-Liquid (Exons: 70 genes; Select Introns: 7 genes) and F-ACT (Exons: 59 genes; Select Introns: 6 genes). Variant zygosity and somatic/germline status (SGZ) for short variant mutations was computationally predicted without matched normal tissue using an investigational method. A Gaussian Mixture Model (GMM) was used to identify latent molecular classes in samples harboring somatic, pathogenic variants (n=613); the Bayesian Information Criteria (BIC) was used for model selection. Results: We identified 1,009 pts with cfDNA based CGP - median age was 65, 55% were male, and median cfDNA concentration was 24 ng/µL. cfDNA yield had an influence on the detection of somatic alterations (p &lt;0.001). 613/1009 (60.8%) of pts had at least one somatic alteration detected on cfDNA based CGP. TP53 (53.7%), KRAS (40.3%) and CDKN2A (6.5%) were the most frequently altered genes (Table1). Homologous Recombination DNA Damage Repair (HR-DDR) gene alterations [somatic and/or germline BRCA2, ATM, and CHEK2 alterations], were detected in 12.3% (124/1009) pts – 11.4% (46/403) in KRAS mutated pts and 12.9% (78/606) in KRAS wildtype (WT) pts. Fusions were detected only in KRAS WT pts (1.5%, 6/403). Pts with cfDNA based CGP could be classified into 4 latent classes – class 1 ( KRAS - 100%, TP53 - 100% and CDKN2A – 33.3%), class 2 ( KRAS - 65.7%), class 3 ( KRAS – 68.2%, CDKN2A/B – 7.7% ) and class 4 ( KRAS – 38.5%, TP53 - 26.7%). Conclusions: The putative role of cfDNA based CGP in monitoring therapeutic response and clonal evolution in pts with PDAC may be predicated on cfDNA yield. In clinical scenarios where pre-treatment tissue availability is limited, cfDNA based CGP may be have utility in leveraging the predictive value of somatic and/or germline HR-DDR gene alterations. The prognostic and/or predictive relevance of the four latent classes needs validation in clinically annotated data sets. [Table: see text]