tbuckley/cabot-search huggingface dataset:
Applying the ASCO and ESMO Value Frameworks to nasopharyngeal cancer treatments: Is adding induction chemotherapy or adjuvant chemotherapy to concurrent chemoradiotherapy worthwhile?
Authors: Teng Hwee Tan, Yu Yang Soon, Timothy Cheo, Lea Choung Wong, Yiat Horng Leong, Jeremy Chee Seong Tey, Francis Ho
Journal: Journal of Clinical Oncology (2020)

67 Background: To determine and compare the incremental clinical benefit (ICB) and costs of induction chemotherapy (IC) when added to concurrent chemoradiotherapy (CCRT), concurrent chemotherapy (CC) added to RT and CC + adjuvant chemotherapy (AC) when added to RT for locally advanced nasopharyngeal cancer (LA-NPC). Methods: We searched phase III randomized controlled trials (RCTs) which reported overall survival (OS) benefit with the use of IC, CC and CC+AC in LA-NPC. We quantified the ICB using the ASCO and ESMO value framework. We calculated the incremental drug costs in US dollars using the lowest average wholesale price reported in the Lexicomp drug database. Results: We identified three RCTs on IC, three RCTs on CC and four RCTs on CC + AC. The ICB was judged to be Grade A based on the ESMO framework. The ASCO Net Health Benefit Score (NHBS) ranged from 17.43 to 57.39. The incremental drug costs ranged from 133.46 to 626.14. There were no statistically significant differences in the means of NHBS [39.37 (IC) vs 37.61 (CC) vs 33.98 (CC+AC), P = 0.89] and costs [383 (IC) vs 253 (CC) vs 460 (CC+AC), P = 0.27] between these three approaches. There was no statistically significant correlation between ICB and costs. Conclusions: The magnitudes of ICB and incremental drug costs of adding of IC to CCRT, CC to RT and CC + AC to RT for LA NPC are not significantly different.
C-CRES: COVID-19 and cancer research engagement study.
Authors: Louis Fox, Harriet Wylie, Fidelma Cahill, Anna Haire, Joyce Kibaru, Saran Green, Catherine Hartley, Richard Sullivan, Mieke Van Hemelrijck
Journal: Journal of Clinical Oncology (2020)

182 Background: Emerging reports suggest that continuation of clinical trials is feasible and safe even in hospitals admitting COVID-19 patients-given the appropriate safety procedures. However, to our knowledge no studies have yet addressed how to again engage patients in cancer research. C-CRES was developed to identify factors that may be affecting participation in cancer research during the COVID-19 pandemic. We aimed to examine patient-specific concerns around research participation. This information will help inform future strategies for mitigating the impact of COVID-19 on cancer research. Methods: Between 5-13 June 2020, we advertised an anonymous survey using our research group’s Twitter account and tagged a variety of cancer patient organisations/charities. Patients aged 18 with a current cancer diagnosis were eligible to participate and asked about their diagnosis/treatment, experience in cancer research, and beliefs about future cancer research participation given the COVID-19 pandemic. We specifically asked about potential concerns relating to research engagement. Results: A total of 75 patients filled out our questionnaire, of whom 89% were UK-based. 65% of respondents were male and the majority was of a white background (89%). The median age category was 60-69 years. 47% of patients had prostate cancer, 15% breast, 12% bladder, and 9% kidney cancer–a reflection of the cancer types our research team focuses on. Interestingly, 49% of participants had never participated previously in research. We therefore set out to make comparisons of patient concerns with regards to research participation during the COVID-19 outbreak between those with and without research experience. Those who had never taken part in research before were more likely to have concerns about currently being on cancer treatment (p=0.02) and about the type of cancer they had been diagnosed with (p≤0.05), with regards to taking part in cancer research during the current COVID-19 outbreak. Conclusions: Those with no prior experience of taking part in cancer research may be more likely to have concerns related to their cancer type and current treatment, in terms of participation during COVID-19. Efforts should be made to reassure potential cancer research participants about safety of participating during the COVID-19 pandemic.
Successful treatment of a persistent duodenal fistula using the Amplatzer septal occluder
Authors: Marco A. D’Assuncao, Fernando L. Mota, Fernando J. S. de Oliveira, Marília N. Ferreira, Mayra M. F. Guedes, Amanda M. B. Ziegler, Raul Cutait
Journal: Endoscopy (2020)

Duodenal fistula is a rare but serious complication of gastrointestinal surgery, abdominal trauma, and iatrogenic procedures in general [1]. It is most commonly seen in critically ill patients at elevated risk of death, and its treatment is associated with great challenges, including repeated episodes of recurrence [2]. Endoscopic closure methods are now becoming more reliable and are already being considered as first-line options in the management of this condition.
Let's Talk About Sex—Biological Sex Is Underreported in Biomaterial Studies
Authors: Bryan D. James, Paxton Guerin, Josephine B. Allen
Journal: Advanced Healthcare Materials (2020)

Precision medicine aims to better individualize healthcare. It requires that biomaterials be designed for the physiological characteristics of a specific patient. To make this a reality, biomaterials research and development must address differences of biological sex. More specifically, biomaterials should be designed with properties optimized and appropriate for male and female patients. In analyzing research articles from seven prominent biomaterials journals, sex as a biological variable is missing from an overwhelming majority of in vitro biomaterial studies. From the survey, the reporting of the sex of primary cell cultures happened only 10.3% of the time. Contributing to this trend is that commercial vendors bias cell lines toward one sex or another by not disclosing information of cell line sex at the time of purchase; researchers do not communicate this pertinent information in published studies; and many journal policies have little to no requirements for reporting cell line characteristics. Omitting this valuable information leads to a gap in the understanding of sex-specific cell-biomaterial interactions and it creates a bias in research findings towards one sex or another. To curb this concerning trend and make precision biomaterials a reality will require the biomaterials field to "talk about sex" by reporting cell sex more broadly.
Junior doctor struck off for dishonesty is restored to medical register
Authors: Clare Dyer
Journal: BMJ (2020)

A junior doctor who was struck off the UK medical register in 2014 for falsifying clinical assessments during his training has won reinstatement to the register.

Eric Brew was an ST4 trainee in acute medicine at Leicester Royal Infirmary in 2011 when he falsified 18 clinical assessment entries after being told that his e-portfolio was inadequate. These related to training done at his previous hospital, Kettering General.

He initially told the annual review of competency panel that the assessments were genuinely from Kettering consultants and that he had taken a week off work and travelled to Kettering …
Machine learning to classify clinically meaningful patient groups by ESAS symptom clusters in oropharyngeal cancer patients undergoing initial treatment.
Authors: Ghazal Haddad, Katrina Hueniken, Scott Victor Bratman, John R de Almeida, David Paul Goldstein, Shao Hui Huang, Aaron Richard Hansen, Andrew J. Hope, Anna Spreafico, Wei Xu, Geoffrey Liu
Journal: Journal of Clinical Oncology (2020)

171 Background: Cancer patients often experience symptoms in clusters, which could contribute to patient outcomes and quality of life; yet most analyses describe only individual symptom scores or a summation of symptom scores rather than symptom clusters. We compared machine learning to traditional statistical methods for grouping patients by symptoms in a heavy symptom burden patient population: oropharyngeal cancer patients undergoing initial treatment with radiation or chemoradiation (C/RT). Methods: K-means clustering was compared to traditional statistical methods (i.e., histogram-analysis; use of quantiles; categorization by clinico-demographic features) for classifying patients based on Edmonton Symptom Assessment System (ESAS) symptom scores in newly diagnosed oropharyngeal cancer patients before and after C/RT initiation. Results: 278 patients were classified into 3 K-means groups at each of two timepoints: pre-C/RT and post-C/RT. These groupings were formed primarily based on differences by symptom burden and were thus labeled: low, moderate, and high symptom-burden patient groups. The table shows dynamic change as patients moved from group to group during C/RT treatment. Greatest symptom-burdens in pre-C/RT patients were anxiety and tiredness; in post-C/RT, poor appetite and tiredness. Chi-squared residuals attributed being female (residuals of -3.95 for low, -2.46 for moderate, and 2.41 for high burden) and HPV-negative cancer (residuals of -1.48, -0.52, and 2.57, respectively) to being associated with higher symptom burden pre-C/RT; no clinico-demographic characteristics were associated with high symptom burden post-C/RT, suggesting this was a previously unidentified patient group. Although separation into K-means clusters in this population was primarily related to symptom burden, K-means better identified the number of patient groups and classified patients at the boundaries between groups (involving up to a quarter of patients) when compared to traditional statistical methods. Conclusions: Machine learning clustering analysis separated patients into discrete groups by symptom burden. K-means provided an objective means for clustering patients in a clinically-meaningful way when compared to traditional statistical methods for grouping patients. [Table: see text]
PI3K Driver Mutations: A Biophysical Membrane-Centric Perspective
Authors: Mingzhen Zhang, Hyunbum Jang, Ruth Nussinov
Journal: Cancer Research (2020)

Ras activates its effectors at the membrane. Active PI3Kα and its associated kinases/phosphatases assemble at membrane regions enriched in signaling lipids. In contrast, the Raf kinase domain extends into the cytoplasm and its assembly is away from the crowded membrane surface. Our structural membrane-centric outlook underscores the spatiotemporal principles of membrane and signaling lipids, which helps clarify PI3Kα activation. Here we focus on mechanisms of activation driven by PI3Kα driver mutations, spotlighting the PI3Kα double (multiple) activating mutations. Single mutations can be potent, but double mutations are stronger: their combination is specific, a single strong driver cannot fully activate PI3K, and two weak drivers may or may not do so. In contrast, two strong drivers may successfully activate PI3K, where one, for example, H1047R, modulates membrane interactions facilitating substrate binding at the active site (
Racial disparities in performance status among cancer patients at a community oncology practice.
Authors: Joanne S. Buzaglo, Alexander Musallam, Edward Stepanski, Craig White, Mary Joiner, Ari M. Vanderwalde, Veronica Decker
Journal: Journal of Clinical Oncology (2020)

132 Background: Performance status is used to characterize patient ability to tolerate chemotherapy and as a selection criterion for clinical research. Poor performance status can exclude patients from clinical trial participation. Further, African American cancer patients are underrepresented in cancer clinical trials. The study purpose was to document performance status at the initial patient visit to a community oncology practice and to explore racial disparities between White and Black patients. Methods: This study used a retrospective, observational design with ePRO collected via the Patient Care Monitor™ (PCM). All study data were collected as part of routine clinical care at a community oncology practice during 1/2019–11/2019. An Eastern Cooperative Oncology Group (ECOG) score was automatically calculated after patients at an initial clinic visit completed a 1-item question that assessed performance status via e-tablet. Results: 6,613 patients completed the PCM survey (mean age 59; 33% male/67% female; 55.4% White, 38% Black). Cancer type was known for a subset of patients (22% breast, 9% hematologic, 4% lung, 5% colorectal, 3% prostate, 11% other types). The average ECOG score for the total sample was 0.97. 50% indicated they were able to complete their normal daily activities without any restriction; 26.9% were able to complete their normal daily activities and some light work. In contrast, 10.3% indicated they could take care of themselves, but could not work and are in bed/chair less than half the day. 10.3% could take care of themselves sometimes but could not work and are in bed/chair more than half the day. 4.5% indicated they could not take care of themselves and were in bed/chair almost always. When assessing racial differences between those self-identifying as White or Black/African American, average ECOG score was higher in Black patients [Mean(SD) = 1.03(1.24)] when compared to White patients [Mean(SD) = 0.93(1.14)] (p = 0.003). We observed a higher percentage of Black patients reported not being able to take care of themselves (51.9% Black v. 41.0% White). In contrast, a higher percentage of White patients reported being able to complete all daily activities without restriction (38.3% Black v. 54.5% White). Conclusions: This study shows significant racial disparities in performance status among patients seen at a community oncology practice with Black patients exhibiting significant worse performance status than White patients. These findings have implications for disparities in treatment outcomes and racially biased access to clinic trials.
038 Respiratory viral infections in Team Finland during 2019 Nordic World SKI Championships: a controlled study
Authors: Maarit Valtonen, Wilma Gronroos, Raakel Luoto, Matti Waris, Matti Uhari, Olli Heinonen, Olli Ruuskanen
Journal: British Journal of Sports Medicine (2020)

BackgroundThe occurrence, etiology and clinical presentation of respiratory viral infections in elite athletes is unclear DesignA prospective controlled follow-up study ObjectiveDo elite athletes have an increase in risk of acute respiratory viral illnesses?SettingWe followed respiratory viral infections in Team Finland during 2019 Nordic World Ski Championships and in sex and age-matched controls in Finland Participants26 athletes, and 36 staff members  52 control subjects were adjusted for age sex and number of children InterventionNasal swabs were taken from team members on days 1, 7 and 13 during the Games which lasted 14 days  Respiratory symptoms were recorded daily  At the onset of a symptom two nasal swabs were taken  One swab was analysed within 60 minutes using a point-of-care test (POCT) for 15 viruses  The other swab was tested for 16 viruses in laboratory ResultsRespiratory viruses were detected in 35%, 36% and 25% of the athletes, the staff members and the controls, respectively  Ten out of 26 (38%) athletes and 6 out of 36 (17%) staff members and 3 out of 52 (6%) controls experienced symptoms of respiratory infection  Asymptomatic infections were identified in 4%, 19% and 21%, respectively  The etiology of respiratory infections was detected in 84% of the cases  Four virus clusters were identified caused by rhinovirus, coronavirus 229E and NL63 and respiratory syncytial virus B  The clinical presentation of the infections in athletes was mild and the median duration of symptoms was 5 5 days  One athlete lost a competition due to a viral respiratory infection ConclusionsThe athletes had a 6-fold increase in risk of illness compared to normally physically active controls  The athletes had significantly less asymptomatic infections compared to staff and controls  Despite the infection prevention protocols, viruses circulated actively within the team
ATAC-Seq Reveals an <i>Isl1</i> Enhancer That Regulates Sinoatrial Node Development and Function
Authors: Giselle Galang, Ravi Mandla, Hongmei Ruan, Catherine Jung, Tanvi Sinha, Nicole R. Stone, Roland S. Wu, Brandon J. Mannion, Prasanna K.R. Allu, Kevin Chang, Ashwin Rammohan, Marie B. Shi, Len A. Pennacchio, Brian L. Black, Vasanth Vedantham
Journal: Circulation Research (2020)

Cardiac pacemaker cells (PCs) in the sinoatrial node (SAN) have a distinct gene expression program that allows them to fire automatically and initiate the heartbeat. Although critical SAN transcription factors, including Isl1 (Islet-1), Tbx3 (T-box transcription factor 3), and Shox2 (short-stature homeobox protein 2), have been identified, the cis-regulatory architecture that governs PC-specific gene expression is not understood, and discrete enhancers required for gene regulation in the SAN have not been identified.To define the epigenetic profile of PCs using comparative ATAC-seq (assay for transposase-accessible chromatin with sequencing) and to identify novel enhancers involved in SAN gene regulation, development, and function.We used ATAC-seq on sorted neonatal mouse SAN to compare regions of accessible chromatin in PCs and right atrial cardiomyocytes. PC-enriched assay for transposase-accessible chromatin peaks, representing candidate SAN regulatory elements, were located near established SAN genes and were enriched for distinct sets of TF (transcription factor) binding sites. Among several novel SAN enhancers that were experimentally validated using transgenic mice, we identified a 2.9-kb regulatory element at the Isl1 locus that was active specifically in the cardiac inflow at embryonic day 8.5 and throughout later SAN development and maturation. Deletion of this enhancer from the genome of mice resulted in SAN hypoplasia and sinus arrhythmias. The mouse SAN enhancer also directed reporter activity to the inflow tract in developing zebrafish hearts, demonstrating deep conservation of its upstream regulatory network. Finally, single nucleotide polymorphisms in the human genome that occur near the region syntenic to the mouse enhancer exhibit significant associations with resting heart rate in human populations.(1) PCs have distinct regions of accessible chromatin that correlate with their gene expression profile and contain novel SAN enhancers, (2) cis-regulation of Isl1 specifically in the SAN depends upon a conserved SAN enhancer that regulates PC development and SAN function, and (3) a corresponding human ISL1 enhancer may regulate human SAN function.
Health care resource utilization (HCRU) and total costs of care (TCOC) among patients (pts) with diffuse large B-cell lymphoma (DLBCL) treated with chimeric antigen receptor (CAR) T-cell therapies in the United States: An analysis of four claims databases.
Authors: Scott J. Keating, Tao Gu, Monika Parisi Jun, Corey Pelletier, Ali McBride
Journal: Journal of Clinical Oncology (2020)

76 Background: Non-Hodgkin lymphoma comprises a heterogenous group of hematologic malignancies, including aggressive lymphomas such as DLBCL. Novel treatment modalities include CAR T cell therapies. Limited real-world data exist on HCRU and costs among pts treated with FDA-approved CAR T cell therapies. Methods: Pts with DLBCL treated with CAR T cell therapies were identified in 4 databases (IBM MarketScan, n = 60; Optum Clinformatics, n = 56; PharMetrics Plus, n = 75; and Humana, n = 14) from September 2017–H2 2019. Mean total, inpatient, outpatient, and pharmacy costs were calculated and adjusted to 2019 US dollars. HCRU and costs were stratified by adverse events (AEs) of interest—cytokine release syndrome (CRS) and neurological events (NEs)—identified through unvalidated “loose” and “strict” criteria. Results: A total of 205 pts were identified. Across databases, mean age ranged from 55.2–68.9 years, 63%−86% were male, and 88%−100% received CAR T cell therapy in the inpatient setting. In the 3 months after CAR+ T cell infusion, mean TCOC for all pts ranged from $353,642−$525,772 across databases (Table); mean TCOC were highest among pts who had CRS ($344,486−$730,224; strict CRS criteria). Mean inpatient length of stay (LOS) ranged from 17−21 days and was longer among pts who had CRS (18−23 days; n = 62) or NEs (20−24 days; n = 89) (strict CRS/NE criteria). Conclusions: HCRU and TCOC among pts with DLBCL treated with CAR T cell therapies were generally higher among pts who experienced CRS or NEs. Payors and health care systems may benefit from considering the total cost of CAR T cell therapy, including HCRU associated with treatment-emergent AEs. [Table: see text]
The duration of infectiousness of individuals infected with SARS-CoV-2
Authors: Kieran A. Walsh, Susan Spillane, Laura Comber, Karen Cardwell, Patricia Harrington, Jeff Connell, Conor Teljeur, Natasha Broderick, Cillian F. de Gascun, Susan M. Smith, Máirín Ryan, Michelle O'Neill
Journal: Journal of Infection (2020)
Factors determining oncology on-call service utilization and implications for quality improvement.
Authors: Marta Wioleta Wronska, Marc Justin Braunstein, Shahidul Islam
Journal: Journal of Clinical Oncology (2020)

213 Background: Most ambulatory oncology practices utilize an on-call service that is essential for continuity of cancer care after office hours, yet there is limited literature about the dynamics of this care delivery model and how to improve it from a quality standpoint. We hypothesize that patients with more advanced cancers are more likely to require the on-call service due to acute symptoms arising during their treatment, and that this information can be used to create a risk model to predict subsequent hospitalization. Methods: We performed a single-center, retrospective review of sequential overnight and weekend calls received by an oncology practice with 16 physicians over a 20-week period from January-May 2020. Calls were classified as being either urgent, requiring immediate attention, or non-urgent, which could be addressed during office hours. Data were summarized using descriptive statistics, continuous and categorical variables were compared using Wilcoxon rank-sum test and Fisher’s exact test, respectively. Multivariate analyses were estimated by logistic regression using the penalized maximum likelihood estimation method. Results: The data set included 236 consecutive calls among 176 patients, with 65% females and median age of 68 (range: 25-87). Of these, 185 calls (78.4%) were deemed urgent, among which 139 (75%) were symptom-related. Among the 202 calls (85%) from patients with cancer, 164 (81%) of them were urgent, mostly due to symptoms (82%). Of these urgent calls, 44 (27%) resulted in admission within 24 hours (P &lt; 0.0001), primarily related to treatment toxicity or disease progression (81%). Patients with stage 4 cancers (42%) or hematologic malignancies (28%) were more likely to use the on-call service. There was no significant difference between call urgency and treatment regimen (P = 0.06). In a multivariable model, advanced age [OR = 1.03(1.0-1.07)] and urgent calls [OR = 33.1(2.7-401.0)] were independently associated with risk of hospitalization. Of note, there were no differences in admissions before or after the peak of the COVID-19 pandemic in New York City (P = 0.49). Conclusions: We identified an association between after-hours calls and more advanced malignancy, which was independent of treatment regimen. The majority of on-call issues were urgent and symptom-related, with advanced age and urgent calls being most likely to result in hospital admission. These results suggest that strategies can be developed to prevent hospitalizations in patients at higher-risk for adverse events based on a multivariable risk model.