tbuckley/cabot-search huggingface dataset:
Disparity in telehealth and emergency department use among Medicaid and commercially insured patients receiving systemic therapy for cancer in Washington State following the COVID-19 Pandemic.
Authors: Scott David Ramsey, Laura Elizabeth Panattoni, Li Li, Qin Sun, Catherine R. Fedorenko, Hayley Sanchez, Karma L. Kreizenbeck, Veena Shankaran
Journal: Journal of Clinical Oncology (2021)

6546 Background: Washington was the first US state to experience the COVID-19 pandemic. Transmission risks and patient fears of visiting oncology practices during its onset resulted in rapid adoption of telehealth services. We hypothesized that the pandemic would widen disparities in oncology practice visits between Medicaid and commercially insured patients, resulting higher rates of emergency department (ED) visits during initial treatment. Methods: Linking Washington State SEER records with Medicaid and commercial insurance enrollment and claims records, we compared adults age &lt;65 with new solid tumor malignancies who received systemic treatment at academic and community oncology practices. Persons starting therapy March – June 2020 (COVID) were compared with those starting therapy March-June 2017-2019 (Pre-COVID). Poisson regressions were used to evaluate differences in oncology practice office visits and telehealth visits. Logistic regressions were used to evaluate the likelihood of at least one ED admission among patients starting systemic therapy pre- and post-COVID. Results: Among patients who met inclusion criteria (652 Commercial, 349 Medicaid), Medicaid enrollees had more advanced disease and more comorbidity versus commercial enrollees. In unadjusted analysis of E&amp;M and telehealth service visit codes, office-based visits fell for both insurance groups (Table) while telehealth service visits (negligible pre-COVID) were higher for commercial versus Medicaid enrollees post-COVID. The proportion of persons with ≥ 1 ED visit during therapy fell for both insurance groups. In Poisson models, Medicaid enrollees had significantly fewer total visits (P=0.001) and fewer telehealth visits (p&lt;0.001) compared commercial enrollees during the COVID period. In the logit models, ED visits trended lower for both groups after COVID (OR 0.53 95% CI 0.279 to 1.008). Among Medicaid enrollees, persons ages 40-49 and breast cancer patients were more likely to visit the ED. Among the commercially insured, persons with 2 or more comorbidities were more likely to visit the ED. The pre-post COVID change in likelihood of an ED visit was not significantly different between insurance groups (p=0.355). Conclusions: In Washington State, the COVID-19 pandemic created a substantial disparity in access to office-based and telehealth care for low-income patients receiving systemic therapy for new cancers. Reduced oncology practice visits among Medicaid patients did not widen existing disparities in utilization of emergency care.[Table: see text]
ADAMANT: a placebo-controlled randomized phase 2 study of AADvac1, an active immunotherapy against pathological tau in Alzheimer’s disease
Authors: Petr Novak, Branislav Kovacech, Stanislav Katina, Reinhold Schmidt, Philip Scheltens, Eva Kontsekova, Stefan Ropele, Lubica Fialova, Milica Kramberger, Natalia Paulenka-Ivanovova, Miroslav Smisek, Jozef Hanes, Eva Stevens, Andrej Kovac, Stanislav Sutovsky, Vojtech Parrak, Peter Koson, Michal Prcina, Jaroslav Galba, Martin Cente, Tomas Hromadka, Peter Filipcik, Juraj Piestansky, Maria Samcova, Carmen Prenn-Gologranc, Roman Sivak, Lutz Froelich, Michal Fresser, Martin Rakusa, John Harrison, Jakub Hort, Markus Otto, Duygu Tosun, Matej Ondrus, Bengt Winblad, Michal Novak, Norbert Zilka
Journal: Nature Aging (2021)
Prevalence of discordant QTc values among cancer patients by the Bazett, Fridericia, and Framingham formulae: Evidence for a standardized approach.
Authors: P. Christopher Parish, Benyam Muluneh, Charles Hicks, Brian Jensen, Joshua F. Zeidner, Daniel R. Richardson
Journal: Journal of Clinical Oncology (2021)

6575 Background: Many chemotherapies have the potential to prolong the QT interval, requiring monitoring of the corrected QT (QTc) to prevent life-threatening arrhythmias. Most clinical guidelines recommend adjusting/holding chemotherapy with Grade 3 or higher toxicity by CTCAE (QTc≥500). Several formulae are used for QTc monitoring including Bazett, Fridericia, and Framingham. The most commonly used formula, Bazett, is well-documented to result in inappropriately high QTc values although the potential impact of this overcorrection on cancer treatment is unknown. We aimed to describe the prevalence of QTc prolongation among cancer patients and the effects on CTCAE adverse event grading by various QTc formulae to determine the potential impact on clinical management. Methods: We performed a single-center retrospective analysis of QT values from electrocardiograms (ECGs) collected January 2010-April 2020 and evaluated associations between QTc values, medications, and patient characteristics. QTc prolonging agents were determined by FDA package insert and cross-referenced with CredibleMeds.org. Results: 20,017 ECGs were evaluated. 18.6% (3,730) met ACC/ACCF/HRS criteria for prolonged QTc by ≥1 QT correction formula (either Bazett, Fridericia, or Framingham). 7.5% (1,494) were prolonged with all three formulae, and 8.6% (1,635) were prolonged only with Bazett. The CTCAE classification using the Bazett formula differed from both Fridericia and Framingham in 37.9% (7,583) of the ECGs. In contrast, Fridericia and Framingham formulae resulted in the same CTCAE classification in 94.5% (18,912). Of 1,789 ECGs classified as Grade 3 toxicity by Bazett, 72.0% (1,288, 6.4% of all ECGs) were classified as Grade 2 or less by both Fridericia and Framingham. 12.0% (2,340) of all ECGs were taken from patients (n = 421) on 24 different QT-prolonging chemotherapies. In 38.8% (909) of the ECGs, the CTCAE classification using the Bazett formula differed from both Fridericia and Framingham while use of Fridericia and Framingham formulae resulted in the same classification in 93.0% (2,176) of the ECGs. Of 293 ECGs classified as Grade 3 toxicity by Bazett, 65.2% (191) were classified as Grade 2 or less by both Fridericia and Framingham. Conclusions: To our knowledge, this is the largest analysis of discrepancies between different QTc formulae in patients receiving chemotherapy. These findings demonstrate an unacceptably high rate of discordance between formulae. Discordant data can lead to inconsistent clinical management and adverse event grading underscoring the urgent need to standardize QTc monitoring and reporting. These findings support the discontinuation of the routine use of the Bazett correction formula among cancer patients as CTCAE Grade 3 reporting from the Bazett formula is unreliable in over 65% of cases.
Real-world data (RWD) reveals benefit for adjuvant chemotherapy with docetaxel, oxaliplatin and fluorouracil/leucovorin (FLOT) is limited to those with tumour regression grade (TRG) ≥3 in oesophago-gastric cancer (OGC).
Authors: Brindley Sonal Hapuarachi, Rebecca Lee, Adeel Khan, Laura Woodhouse, Valentinos Kounnis, Fiona Britton, Jessica Coyle, Kathleen Connors, Neethu Billy Graham Mariam, Jamie Weaver, Tom Waddell, Richard Hubner, Konstantinos Kamposioras, Wasat Mansoor
Journal: Journal of Clinical Oncology (2021)

4039 Background: Despite potentially curative surgery, long-term survival from OGC remains poor due to high relapse rate. Neoadjuvant (naFLOT) and adjuvant (aFLOT) FLOT is currently standard treatment for resectable OGC based on data from the FLOT-4 trial. We explored whether TRG was associated with FLOT-outcome using RWD. Methods: Pts with OGC treated with naFLOT +/- aFLOT at a tertiary UK centre were identified following institutional board approval. Clinical and laboratory data were extracted from the patient record. TRG was evaluated by a histopathologist. Median overall survival (OS) and median progression-free survival (PFS) were evaluated using Kaplan-Meier and Log-rank tests; time taken from start of naFLOT, and associations between factors with Fisher’s exact (FE) test. Results: 171 pts were identified, median FU 30 mths. 144 (84%) male; median age 66 (32-84); oesophagus 66 (38%), junctional (GOJ) 73 (43%), gastric 32 (19%); stage IB 3 (2%), stage IIB 26 (15%), stage III 91 (53%), stage IVA 47 (28%) and unknown 4 (2%). Pts had median of 2 comorbidities (range 0-6); performance status (PS) 0: 95 (56%), PS 1: 71 (41%), PS 2: 3 (2%) and PS unknown 2 (1%). 132/171 pts completed 4 cycles of naFLOT and this was significantly associated with undergoing surgery (p = 0.02). Those who had surgery (140/171) had significantly improved PFS (not reached (NR) vs. 6 mths; 95% CI 2-10; p &lt; 0.001) and OS (NR vs. 12 mths; 95% CI 6-18; p &lt; 0.001). TRG was reported for 126/140 patients who underwent surgery. TRG 1/2 (42/126) vs. TRG ≥3 was significantly associated with improved PFS (NR vs. 35 mths; 95% CI NR; p &lt; 0.001) and OS (median NR either group; p &lt; 0.001). Pts with TRG 1/2 who commenced aFLOT (≥1 cycle; n = 31/42) or completed 4 cycles of aFLOT (17/31) did not have improved PFS or OS vs. those who did not. Those with TRG ≥3 who commenced aFLOT (≥1 cycle; n = 62/85) had improved PFS (median NR vs. 22 mths; 95% CI 13-31 p = 0.006) and OS (median NR vs. 25 mths; 95% CI 18-32 p = 0.019). Those with TRG ≥3 who completed 4 cycles of aFLOT (n = 38/62) had significantly improved PFS (median NR vs. 25 mths; 95% CI 14-36 p = 0.016) and OS (median NR vs. 36 mths; 95% CI 16-55 p = 0.012). There was no difference in PFS or OS in pts with TRG ≥3 who had a dose reduction at any time during aFLOT. Conclusions: TRG is a predictor of outcome following naFLOT + surgery with superior outcomes in those with TRG 1/2. Our analyses suggest that only pts with TRG &gt;3 following naFLOT + surgery benefit from adjuvant FLOT. Prospective randomised studies are required to confirm whether pts with TRG 1/2 require treatment with aFLOT.
Plasticity of the human preimplantation embryo: developmental dogmas, variations on themes and self-correction
Authors: Giovanni Coticchio, Amy Barrie, Cristina Lagalla, Andrea Borini, Simon Fishel, Darren Griffin, Alison Campbell
Journal: Human Reproduction Update (2021)

Abstract BACKGROUND IVF for the treatment of infertility offers unique opportunities to observe human preimplantation development. Progress in time-lapse technology (TLT) and preimplantation genetic testing (PGT) has greatly expanded our knowledge of developmental patterns leading to a healthy pregnancy or developmental failure. These technologies have also revealed unsuspected plastic properties of the preimplantation embryo, at macromolecular, cellular and multicellular levels. OBJECTIVE AND RATIONALE This review focuses on the emerging concept of plasticity of the human embryo as revealed by recent evidence derived from TLT and PGT, calling for an updated and more precise redefinition of the boundaries between normal and abnormal development. SEARCH METHODS PubMed was used to search the MEDLINE database for peer-reviewed English-language original articles and reviews concerning human preimplantation development. Cross-searches were performed by adopting ‘fertilisation‘, ‘pronucleus’, ‘cleavage’, ‘multinucleation’, ‘compaction’, ‘embryo’, ‘preimplantation genetic testing’, ‘aneuploidy’, mosaicism’, ‘micromanipulation’, ‘time-lapse microscopy’ and ‘IVF/assisted reproduction’ as main terms. The most relevant publications, i.e. those concerning major phenomena occurring during normal and abnormal development—with a focus on the human species—were assessed and discussed critically. OUTCOMES Advances in TLT and PGT have revealed an astonishing plasticity and self-correction ability of the human preimplantation embryo in vitro. At fertilisation, an abnormal number of pronuclei do not always result in the formation of an aneuploid blastocyst. Animal studies and preliminary human observations indicate that combining of parental genomes may occur at the early cleavage stage, if not at fertilisation. Multinucleation occurs with much higher prevalence than previously thought and may be corrected at later cleavage stages. Irregular cleavage (multichotomous, direct, rapid and reverse cleavages) can generate chromosome segregation abnormalities that often lead to developmental arrest, but that sporadically may be confined to cells excluded from the blastocyst, and may sometimes result in viable pregnancy. Mitotic errors can generate mosaic blastocysts, but alternatively normal embryos may form from selective death or clonal depletion of aneuploid cells. WIDER IMPLICATIONS Deviations from developmental dogmas and the increasing evidence of plasticity of the human embryo challenge current embryological notions and suggest the need to write new rules governing cell cycle, cell determination and chromosome segregation during preimplantation development.
Immunotherapy in patients with lung cancer with driver mutations: A single center experience.
Authors: Prathyush Vundemodalu, Amit Rauthan, Poonam Patil, Rajashri Aswath
Journal: Journal of Clinical Oncology (2021)

e21170 Background: Immunotherapy has revolutionized treatment in metastatic non small cell lung cancer (NSCLC)without driver mutations. Trial data shows that programme death-1/ PDL1 blockade in epidermal growth factor receptor(EGFR) and other driver mutation positive lung cancers is not beneficial. Here we evaluated the efficacy of immune check point inhibitors in a series of patients with EGFR and other driver mutation positive advanced NSCLC. Methods: We retrospectively analysed 75 patients who received PD1/ PDL1 inhibitors for advanced NSCL between January 2017 to January 2020. 10 patients were detected to have driver mutations on either tumor tissue or blood by NGS. Results: Out of 10 patients, 7 were male and 3 were female. EGFR was detected in 6 patients (3 on tumor and 3 in blood NGS). We found MET exon 14 skip mutation in 2 and RAS in 2 patients. Immunotherapy combined with chemotherapy was given in 5(50%) patients, immunotherapy + bevacizumab+chemotherapy in 2(20%) and immunotherapy alone in 3 patients(30%). Immunotherapy was as started as first line in 4 patients as tumor tissue was negative for EGFR, ALK, ROS1 by single gene testing. On NGS testing at progression, EGFR mutation was detected in 1 patient, MET exon 14 skip mutation was detected in 2 and Ras mutation in 2 patients. Immunotherapy alone was used in 3 patients in view of advanced age and multiple comorbidities.The progression free survival(PFS) ranged between 2 to 11months. Conclusions: Single agent checkpoint inhibitors seem to have a limited impact in treatment in patients with driver mutations. Molecular testing by NGS is recommended either on tumor tissue or on blood by NGS if single gene testing for EGFR/ ALK/ ROS1 alterations is negative. We do see benefit in patients who received PD1/PDL1 inhibitors in combination with chemotherapy with/ without Bevacizumab. In conclusion, patients progressing on EGFR TKIs who are planned for immunotherapy should always be given in combination with chemotherapy+/- Bevacizumab.[Table: see text]
Impact of endocrine therapy on overall survival in ER negative/PR positive locoregional breast cancer: An analysis of the National Cancer Database.
Authors: Vidya Kollu, Kohei Osterloth, Andrew J. Borgert, Susan M. Frankki, Benjamin Marshall Parsons
Journal: Journal of Clinical Oncology (2021)

545 Background: Breast cancer expressing PR, but not ER (ER-/PR+) are uncommon, comprising 2–8% of breast cancers, with less known about their characteristics and responsiveness to therapy. The role of adjuvant endocrine therapy (ET) in ER-/PR+ locoregional breast cancer is unclear as these patients have been largely excluded from prospective clinical trials. Despite a lack of data patients are often treated with adjuvant ET due to perceived possible benefit. We used the National Cancer Data Base (NCDB) to assess role of adjuvant ET in ER-/PR + breast cancer. Methods: Using the NCDB, we included adults ≥ 18 and ≤ 70 years old in order to minimize the non-cancer related deaths. We selected only female patients with stage I, II, and III. Patients have received definitive surgery (lumpectomy with radiation or mastectomy) with negative margins. Systemic therapy (ST) was defined as receipt of chemotherapy and/or immunotherapy. We excluded those who had unknown ST status, unknown ET status, unknown HER 2 status, who did not receive definitive surgery and those whose survival time was missing. Patients were stratified into four groups based on HER2 status and receipt of ET. Both Multivariable Cox proportional hazards regression modeling was utilized to determine predictors of overall survival (OS). A propensity score matched cohort was developed based on relevant demographic and clinical factors. The primary endpoint assessed was OS. All analyses were performed using SAS 9.4. Results: We identified 5344 patients (74% were Caucasian, 20% were African American and 6% were others) with ER-/PR+(74% were HER2 - and 26% were HER2 +) locoregional breast cancer (51% were Stage I, 38 % were stage II and 11% were stage III). Grade 1 cancer was seen in 2%, grade 2 in 18%, and majority being grade 3 in 80%. Of which 3093 (58%) patients received ET and 4462 (83%) received ST. Majority of patients were in age group 50-70 comprising of 69% patients, 8 % in age 18—39, 23% in age 40-49 with Charlson-Deyo Score of 0 in 83%, 1 in13%, 2-3 in 4%. In a propensity matched cohort (N=3980), ET was not significantly associated with OS among HER2 negative (HER2-) patients (HR=1.05, 95% CI 0.86-1.28, p=0.63). In HER2+ patient ET was associated with significantly improved OS (HR=0.65, 95% CI 0.42-0.99, p=.047). Conclusions: Receiving ET was not associated with improved OS in locoregional ER-/PR+/HER2- breast cancer based on our study using a propensity matched cohort in the NCDB. However, was frequently administered. Interestingly, improved OS was seen in locoregional ER-/PR+/HER2+ breast cancer with adjuvant ET.
Public health impact of delaying second dose of BNT162b2 or mRNA-1273 covid-19 vaccine: simulation agent based modeling study (vol 373, n1087, 2021)
Authors: S. Romero-Brufau, A. Chopra, A. J. Ryu, E. Gel, R. Raskar, W. Kremers, K. S. Anderson, J. Subramanian, B. Krishnamurthy, A. Singh, K. Pasupathy, Y. Dong, J. C. O'Horo, W. R. Wilson, O. Mitchell, T. C. Kingsley
Journal: BMJ (2021)

OBJECTIVE To estimate population health outcomes with delayed second dose versus standard schedule of SARS-CoV-2 mRNA vaccination. DEsIGN Simulation agent based modeling study. SETTING Simulated population based on real world US county. PARTICIPANTs The simulation included 100 000 agents, with a representative distribution of demographics and occupations. Networks of contacts were established to simulate potentially infectious interactions though occupation, household, and random interactions. INTERVENTIONs Simulation of standard covid-19 vaccination versus delayed second dose vaccination prioritizing the first dose. The simulation runs were replicated 10 times. Sensitivity analyses included first dose vaccine efficacy of 50%, 60%, 70%, 80%, and 90% after day 12 post-vaccination;vaccination rate of 0.1%, 0.3%, and 1% of population per day;assuming the vaccine prevents only symptoms but not asymptomatic spread (that is, non-sterilizing vaccine);and an alternative vaccination strategy that implements delayed second dose for people under 65 years of age, but not until all those above this age have been vaccinated. MAIN OUTCOME MEAsUREs Cumulative covid-19 mortality, cumulative SARS-CoV-2 infections, and cumulative hospital admissions due to covid-19 over 180 days. REsULTs Over all simulation replications, the median cumulative mortality per 100 000 for standard dosing versus delayed second dose was 226 v 179, 233 v 207, and 235 v 236 for 90%, 80%, and 70% first dose efficacy, respectively. The delayed second dose strategy was optimal for vaccine efficacies at or above 80% and vaccination rates at or below 0.3% of the population per day, under both sterilizing and non sterilizing vaccine assumptions, resulting in absolute cumulative mortality reductions between 26 and 47 per 100 000. The delayed second dose strategy for people under 65 performed consistently well under all vaccination rates tested. CONCLUsIONs A delayed second dose vaccination strategy, at least for people aged under 65, could result in reduced cumulative mortality under certain conditions.
Dietary fiber intake, the gut microbiome, and chronic systemic inflammation in a cohort of adult men
Authors: Wenjie Ma, Long H. Nguyen, Mingyang Song, Dong D. Wang, Eric A. Franzosa, Yin Cao, Amit Joshi, David A. Drew, Raaj Mehta, Kerry L. Ivey, Lisa L. Strate, Edward L. Giovannucci, Jacques Izard, Wendy Garrett, Eric B. Rimm, Curtis Huttenhower, Andrew T. Chan
Journal: Genome Medicine (2021)

Abstract Background A higher intake of dietary fiber is associated with a decreased risk of chronic inflammatory diseases such as cardiovascular disease and inflammatory bowel disease. This may function in part due to abrogation of chronic systemic inflammation induced by factors such as dysbiotic gut communities. Data regarding the detailed influences of long-term and recent intake of differing dietary fiber sources on the human gut microbiome are lacking. Methods In a cohort of 307 generally healthy men, we examined gut microbiomes, profiled by shotgun metagenomic and metatranscriptomic sequencing, and long-term and recent dietary fiber intake in relation to plasma levels of C-reactive protein (CRP), an established biomarker for chronic inflammation. Data were analyzed using multivariate linear mixed models. Results We found that inflammation-associated gut microbial configurations corresponded with higher CRP levels. A greater intake of dietary fiber was associated with shifts in gut microbiome composition, particularly Clostridiales, and their potential for carbohydrate utilization via polysaccharide degradation. This was particularly true for fruit fiber sources (i.e., pectin). Most striking, fiber intake was associated with significantly greater CRP reduction in individuals without substantial Prevotella copri carriage in the gut, whereas those with P. copri carriage maintained stable CRP levels regardless of fiber intake. Conclusions Our findings offer human evidence supporting a fiber-gut microbiota interaction, as well as a potential specific mechanism by which gut-mediated systemic inflammation may be mitigated.
Decreases in COVID-19 Cases, Emergency Department Visits, Hospital Admissions, and Deaths Among Older Adults Following the Introduction of COVID-19 Vaccine — United States, September 6, 2020–May 1, 2021
Authors: Athalia Christie, S. Jane Henley, Linda Mattocks, Robyn Fernando, Amy Lansky, Farida B. Ahmad, Jennifer Adjemian, Robert N. Anderson, Alison M. Binder, Kelly Carey, Deborah L. Dee, Taylor Dias, William M. Duck, Denise M. Gaughan, Brianna Casey Lyons, A.D. McNaghten, Meeyoung M. Park, Hannah Reses, Loren Rodgers, Katharina Van Santen, David Walker, Michael J. Beach
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

By May 2021, 69%, 45%, and 26% of adults aged ≥65, 50–64, and 18–49 years were vaccinated. From November–December 2020 to April–May 2021, the rate ratios of COVID-19 incidence, emergency department visits, hospital admissions, and deaths among persons aged ≥65 to persons aged 18–49 years declined 40%, 59%, 65%, and 66%, respectively.