tbuckley/cabot-search huggingface dataset:
The changing demographics of COVID-19
Authors: Priya Venkatesan
Journal: The Lancet Respiratory Medicine (2020)

As societies around the world begin to reopen after many months of lockdown, a worrying shift is emerging in the demographic of COVID-19 cases towards individuals aged younger than 40 years. According to an analysis of 6 million cases between February and July, 2020, the number of infected people aged 15–24 years increased from 4·5% to 15%, possibly resulting from a combination of increased socialising in younger age groups and reversion to previous routines, including attending workplaces, schools, and universities, plus better surveillance.
Assessment of Prescription Analgesic Use in Older Adults With and Without Chronic Kidney Disease and Outcomes
Authors: Yun Han, Rajesh Balkrishnan, Richard A. Hirth, David W. Hutton, Kevin He, Diane E. Steffick, Rajiv Saran
Journal: JAMA Network Open (2020)

Pain is a common symptom among patients with kidney disease. However, little is known about use of analgesics among patients aged 65 years or older with chronic kidney disease (CKD) who do not receive dialysis treatment.To assess national trends and geographic variations in use of opioids and prescription nonsteroidal anti-inflammatory drugs (NSAIDs) in older adults with and without CKD in the US (2006-2015) and examine associations between use of opioids and patient outcomes.This cohort study used the 5% Medicare claims data (2005-2015) to select 10 retrospective annual cohorts of Medicare Part D beneficiaries aged 65 years and older from 2006 to 2015 and a retrospective longitudinal cohort. Data were analyzed in August 2019.CKD status and other comorbidities identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes.Analgesic use was measured by overall use (proportion of ever used opioids/NSAIDs), long-term use (prescribed >90 days), and cumulative use (total annual days' supply). Patient outcomes included progression to end-stage kidney disease (ESKD) and all-cause mortality.A total of 6 260 454 beneficiaries (9.6% identified with CKD by claims) were selected in the annual cohorts and 649 339 beneficiaries (8.3% identified with CKD) were selected in the longitudinal cohort. There was significant growth in opioid use (31.2%-42.4%) and NSAID use (10.7%-16.6%) among patients aged 65 years and older with CKD from 2006 to 2015. Long-term use of opioids increased during 2006 to 2014 (25.8%-36.7%) but decreased through 2015 at 35.6%, while long-term use of NSAIDs remained stable. Opioid use was higher in patients with CKD, particularly CKD stages 4 to 5 (odds ratio [OR], 1.35; 95% CI, 1.33-1.37; P < .001) compared with non-CKD. NSAID use was lower in patients with CKD stages 4 to 5 (OR, 0.55; 95% CI, 0.54-0.56; P < .001). Substantial geographic variations in analgesic use were observed across states (opioid use in CKD: 24.7%-54.3%; NSAID use in CKD: 11.2%-20.8%, 2012-2015). Opioid use was associated with progression to ESKD (hazard ratio [HR], 1.10; 95% CI, 1.04-1.16; P = .001) and death (HR, 1.19; 95% CI, 1.18-1.20; P < .001) independent of CKD status and other covariates. There was an inverse association between NSAID use and death (HR, 0.84; 95% CI, 0.83-0.85; P < .001).Among Medicare patients with CKD, use of prescription analgesics, both opioid and NSAID, increased from 2006 to 2015. Optimizing pain management in a complex condition such as kidney disease should remain a priority for clinicians and researchers alike.
Pause in breast cancer screening is opportunity to re-evaluate programme, says critic
Authors: Shaun Griffin
Journal: BMJ (2020)

Figures showing that a million women in the UK missed mammograms after breast screening programmes were paused in March have reignited the debate about whether breast cancer screening does more harm than good.

While the charity Breast Cancer Now has said that the programme should not be paused again, others see the six month gap in screening as an opportunity to reconsider criticisms of the screening programme and evaluate whether to modify it.

Breast Cancer Now has estimated that around 986 000 women in the UK missed mammograms since March, when services were stopped in an effort to reduce the spread of covid-19 and release emergency NHS resources.1

More than 2 million women are normally screened in the UK …
Predicting Pneumothorax Outcome By Air Leak Measurement: Pilot Using Digital Suction Device
Authors: R J Hallifax, J P Corcoran, N M Rahman
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Introduction  Spontaneous pneumothorax (SP) is common, with an estimated incidence of 5,000 per year in the UK. Primary spontaneous pneumothorax (PSP) can be managed with needle aspiration initially but those who fail to re-expand, and the majority of secondary SP (SSP), require admission to hospital, insertion of a chest drain and connexion to a bulky underwater drainage system. Patients with SSP have greater co-morbidities; have a long hospital stay (14–16 days) and a mortality of ~16%. There are no good predictors of outcome for patients with pneumothorax: those who will respond to drainage, those who have persistent air leak and those who will require surgery. Significant early air leak could be indicative of those patients who will not resolve spontaneously and will require surgery.  Aim  To determine whether air leak measurement can predict patient outcome (surgical referral rate).  Methods  Between December 2012 and June 2013, patients with pneumothorax managed on the Respiratory Ward of a tertiary referral centre had their “air leak” measured using a digital suction device (Thopaz, Medela UK).  Results  A total of nine patients (6 SSP, 2 PSP, and 1 iatrogenic) were investigated. Air leak was measured during their in-patient stay: median of 3.5 days after admission (range 1–16 days). Three (33%) were referred for surgical intervention for continued air leak and pneumothorax: their average air leak was 504ml/min (range 222–952 ml/min) compared to 77 ml/min (range 1–225 ml/min) for the six patients not referred. The 427ml/min difference was not statistically significant (p = 0.2) with this sample size.  Conclusion  At present, there are no good predictors of outcome for patients with pneumothorax. Air leak measurement post-drain insertion may be useful surrogate marker for on-going leak and hence non-resolving pneumothorax. This pilot study showed a difference in early leak measurement between those patients who were ultimately referred for surgery and those spontaneously resolving, and further larger studies are now warranted, comparing air leak to clinically important outcomes in pneumothorax.
From Tissue-Agnostic to N-of-One Therapies: (R)Evolution of the Precision Paradigm
Authors: Jacob J. Adashek, Vivek Subbiah, Razelle Kurzrock
Journal: Trends in cancer (2020)

Next-generation sequencing has led to four tissue-agnostic FDA approvals, including for gene- and immune-targeted agents for patients with cancerHigh levels of tumor heterogeneity and genomic complexity that differ from patient to patient suggest that individualized N-of-one therapy combinations are a necessary next step for treatment optimizationReal-world data and advanced digital data mining has already been used for more FDA approvals and are likely to result in more in the future Precision medicine has exploited next-generation sequencing (NGS) and gene/immune-targeted drug deployment to transform the outlook for several lethal cancers. For instance, there are now several FDA-approved medications that target the sequelae of aberrant genes in a tissue-agnostic approach: pembrolizumab [microsatellite instability and tumor mutational burden (TMB) ≥10 mutations/megabase (mut/Mb)] and larotrectinib/entrectinib (NTRK fusions). Molecular interrogation further reveals the disruptive reality that metastatic cancers are tremendously complex and individually distinct. Therefore, optimized treatment often requires drug combinations (rather than monotherapy) and N-of-one customization. Early studies of this approach suggest feasibility, safety, and efficacy. Real-world data/master registry trials may also provide massive, clinically relevant datasets that further fuel the (r)evolution in oncology. Precision medicine has exploited next-generation sequencing (NGS) and gene/immune-targeted drug deployment to transform the outlook for several lethal cancers. For instance, there are now several FDA-approved medications that target the sequelae of aberrant genes in a tissue-agnostic approach: pembrolizumab [microsatellite instability and tumor mutational burden (TMB) ≥10 mutations/megabase (mut/Mb)] and larotrectinib/entrectinib (NTRK fusions). Molecular interrogation further reveals the disruptive reality that metastatic cancers are tremendously complex and individually distinct. Therefore, optimized treatment often requires drug combinations (rather than monotherapy) and N-of-one customization. Early studies of this approach suggest feasibility, safety, and efficacy. Real-world data/master registry trials may also provide massive, clinically relevant datasets that further fuel the (r)evolution in oncology.
Short or Long Sleep Duration and CKD: A Mendelian Randomization Study
Authors: Sehoon Park, Soojin Lee, Yaerim Kim, Yeonhee Lee, Min Woo Kang, Kwangsoo Kim, Yong Chul Kim, Seung Seok Han, Hajeong Lee, Jung Pyo Lee, Kwon Wook Joo, Chun Soo Lim, Yon Su Kim, Dong Ki Kim
Journal: Journal of the American Society of Nephrology (2020)

Significance Statement Poor sleep is known to be related to kidney function impairment. Using the UK Biobank cohort, including individuals self-reporting regular sleep patterns of short, intermediate, or long duration, the authors found that short or long sleep duration was associated with higher prevalence of CKD. In the genetic analysis, the genetic risk score for short but not long sleep duration was significantly related to a higher risk of CKD stages 3–5, suggesting causal effects of short sleep duration on CKD. Two-sample Mendelian randomization analysis, using the independent meta-analysis results of kidney function from the CKDGen Consortium genome-wide association study, also showed significant causal estimates of short sleep duration on CKD. Clinicians may thus consider encouraging patients to avoid short-duration sleeping behavior to reduce the risk of CKD. Background Studies have found sleeping behaviors, such as sleep duration, to be associated with kidney function and cardiovascular disease risk. However, whether short or long sleep duration is a causative factor for kidney function impairment has been rarely studied. Methods We studied data from participants aged 40–69 years in the UK Biobank prospective cohort, including 25,605 self-reporting short-duration sleep (&lt;6 hours per 24 hours), 404,550 reporting intermediate-duration sleep (6–8 hours), and 35,659 reporting long-duration sleep (≥9 hours) in the clinical analysis. Using logistic regression analysis, we investigated the observational association between the sleep duration group and prevalent CKD stages 3–5, analyzed by logistic regression analysis. We performed Mendelian randomization (MR) analysis involving 321,260 White British individuals using genetic instruments (genetic variants linked with short- or long-duration sleep behavior as instrumental variables). We performed genetic risk score analysis as a one-sample MR and extended the finding with a two-sample MR analysis with CKD outcome information from the independent CKDGen Consortium genome-wide association study meta-analysis. Results Short or long sleep duration clinically associated with higher prevalence of CKD compared with intermediate duration. The genetic risk score for short (but not long) sleep was significantly related to CKD (per unit reflecting a two-fold increase in the odds of the phenotype; adjusted odds ratio, 1.80; 95% confidence interval, 1.25 to 2.60). Two-sample MR analysis demonstrated causal effects of short sleep duration on CKD by the inverse variance weighted method, supported by causal estimates from MR-Egger regression. Conclusions These findings support an adverse effect of a short sleep duration on kidney function. Clinicians may encourage patients to avoid short-duration sleeping behavior to reduce CKD risk.
Plasma ACE2 and risk of death or cardiometabolic diseases: a case-cohort analysis
Authors: Sukrit Narula, Salim Yusuf, Michael Chong, Chinthanie Ramasundarahettige, Sumathy Rangarajan, Shrikant I Bangdiwala, Martin van Eikels, Kirsten Leineweber, Annie Wu, Marie Pigeyre, Guillaume Paré
Journal: The Lancet (2020)

Angiotensin-converting enzyme 2 (ACE2) is an endogenous counter-regulator of the renin-angiotensin hormonal cascade. We assessed whether plasma ACE2 concentrations were associated with greater risk of death or cardiovascular disease events.We used data from the Prospective Urban Rural Epidemiology (PURE) prospective study to conduct a case-cohort analysis within a subset of PURE participants (from 14 countries across five continents: Africa, Asia, Europe, North America, and South America). We measured plasma concentrations of ACE2 and assessed potential determinants of plasma ACE2 levels as well as the association of ACE2 with cardiovascular events.We included 10 753 PURE participants in our study. Increased concentration of plasma ACE2 was associated with increased risk of total deaths (hazard ratio [HR] 1·35 per 1 SD increase [95% CI 1·29-1·43]) with similar increases in cardiovascular and non-cardiovascular deaths. Plasma ACE2 concentration was also associated with higher risk of incident heart failure (HR 1·27 per 1 SD increase [1·10-1·46]), myocardial infarction (HR 1·23 per 1 SD increase [1·13-1·33]), stroke (HR 1·21 per 1 SD increase [1·10-1·32]) and diabetes (HR 1·44 per 1 SD increase [1·36-1·52]). These findings were independent of age, sex, ancestry, and traditional cardiac risk factors. With the exception of incident heart failure events, the independent relationship of ACE2 with the clinical endpoints, including death, remained robust after adjustment for BNP. The highest-ranked determinants of ACE2 concentrations were sex, geographic ancestry, and body-mass index (BMI). When compared with clinical risk factors (smoking, diabetes, blood pressure, lipids, and BMI), ACE2 was the highest ranked predictor of death, and superseded several risk factors as a predictor of heart failure, stroke, and myocardial infarction.Increased plasma ACE2 concentration was associated with increased risk of major cardiovascular events in a global study.Canadian Institute of Health Research, Heart & Stroke Foundation of Canada, and Bayer.
National Variation in Congenital Heart Surgery Outcomes
Authors: Sara K. Pasquali, Dylan Thibault, Sean M. O’Brien, Jeffrey P. Jacobs, J. William Gaynor, Jennifer C. Romano, Michael Gaies, Kevin D. Hill, Marshall L. Jacobs, David M. Shahian, Carl L. Backer, John E. Mayer
Journal: Circulation (2020)

Background: Optimal strategies to improve national congenital heart surgery outcomes and reduce variability across hospitals remain unclear. Many policy and quality improvement efforts have focused primarily on higher-risk patients and mortality alone. Improving our understanding of both morbidity and mortality and current variation across the spectrum of complexity would better inform future efforts. Methods: Hospitals participating in the Society of Thoracic Surgeons Congenital Heart Surgery Database (2014–2017) were included. Case mix–adjusted operative mortality, major complications, and postoperative length of stay were evaluated using Bayesian models. Hospital variation was quantified by the interdecile ratio (IDR, upper versus lower 10%) and 95% credible intervals (CrIs). Stratified analyses were performed by risk group (Society of Thoracic Surgeons–European Association for Cardiothoracic Surgery [STAT] category) and simulations evaluated the potential impact of reductions in variation. Results: A total of 102 hospitals (n=84 407) were included, representing ≈85% of US congenital heart programs. STAT category 1 to 3 (lower risk) operations comprised 74% of cases. All outcomes varied significantly across hospitals: adjusted mortality by 3-fold (upper versus lower decile 5.0% versus 1.6%, IDR 3.1 [95% CrI 2.5–3.7]), mean length of stay by 1.8-fold (19.2 versus 10.5 days, IDR 1.8 [95% CrI 1.8–1.9]), and major complications by &gt;3-fold (23.5% versus 7.0%, IDR 3.4 [95% CrI 3.0–3.8]). The degree of variation was similar or greater for low- versus high-risk cases across outcomes, eg, ≈3-fold mortality variation across hospitals for STAT 1 to 3 (IDR 3.0 [95% CrI 2.1–4.2]) and STAT 4 or 5 (IDR 3.1 [95% CrI 2.4–3.9]) cases. High-volume hospitals had less variability across outcomes and risk categories. Simulations suggested potential reductions in deaths (n=282), major complications (n=1539), and length of stay (101 183 days) over the 4-year study period if all hospitals were to perform at the current median or better, with 37% to 60% of the improvement related to the STAT 1 to 3 (lower risk) group across outcomes. Conclusions: We demonstrate significant hospital variation in morbidity and mortality after congenital heart surgery. Contrary to traditional thinking, a substantial portion of potential improvements that could be realized on a national scale were related to variability among lower-risk cases. These findings suggest modifications to our current approaches to optimize care and outcomes in this population are needed.
Large-Scale 3D Two-Photon Imaging of Molecularly Identified CA1 Interneuron Dynamics in Behaving Mice
Authors: Tristan Geiller, Bert Vancura, Satoshi Terada, Eirini Troullinou, Spyridon Chavlis, Grigorios Tsagkatakis, Panagiotis Tsakalides, Katalin Ócsai, Panayiota Poirazi, Balázs J. Rózsa, Attila Losonczy
Journal: Neuron (2020)
Multiple myeloma current treatment algorithms
Authors: S. Vincent Rajkumar, Shaji Kumar
Journal: Blood Cancer Journal (2020)

Abstract The treatment of multiple myeloma (MM) continues to evolve rapidly with arrival of multiple new drugs, and emerging data from randomized trials to guide therapy. Along the disease course, the choice of specific therapy is affected by many variables including age, performance status, comorbidities, and eligibility for stem cell transplantation. In addition, another key variable that affects treatment strategy is risk stratification of patients into standard and high-risk MM. High-risk MM is defined by the presence of t(4;14), t(14;16), t(14;20), gain 1q, del(17p), or p53 mutation. In this paper, we provide algorithms for the treatment of newly diagnosed and relapsed MM based on the best available evidence. We have relied on data from randomized controlled trials whenever possible, and when appropriate trials to guide therapy are not available, our recommendations reflect best practices based on non-randomized data, and expert opinion. Each algorithm has been designed to facilitate easy decision-making for practicing clinicians. In all patients, clinical trials should be considered first, prior to resorting to the standard of care algorithms we outline.
Affinity-Restricted Memory B Cells Dominate Recall Responses to Heterologous Flaviviruses
Authors: Rachel Wong, Julia A. Belk, Jennifer Govero, Jennifer L. Uhrlaub, Dakota Reinartz, Haiyan Zhao, John M. Errico, Lucas D’Souza, Tyler J. Ripperger, Janko Nikolich-Zugich, Mark J. Shlomchik, Ansuman T. Satpathy, Daved H. Fremont, Michael S. Diamond, Deepta Bhattacharya
Journal: Immunity (2020)
Validation of serum fibrosis marker panels in patients with primary sclerosing cholangitis (PSC) in a randomized trial of simtuzumab
Authors: C L Bowlus, K Patel, I N Guha, R W Chapman, O Chazouilleres, N P Chalasani, J M Vierling, R P Myers, D Ding, Schall Rea., M Subramanian, J G McHutchison, A J Muir, Z D Goodman, C Levy
Journal: Hepatology (2015)
Phase I Study of Alvocidib Followed by 7+3 (Cytarabine + Daunorubicin) in Newly Diagnosed Acute Myeloid Leukemia
Authors: Joshua F. Zeidner, Daniel J. Lee, Mark Frattini, Gil D. Fine, Judy Costas, Kathryn Kolibaba, Stephen P. Anthony, David Bearss, B. Douglas Smith
Journal: Clinical Cancer Research (2020)

Alvocidib is a cyclin-dependent kinase 9 inhibitor leading to downregulation of the antiapoptotic BCL-2 family member, MCL-1. Alvocidib has shown clinical activity in a timed sequential regimen with cytarabine and mitoxantrone in relapsed/refractory and newly diagnosed acute myeloid leukemia (AML) but has not been studied in combination with traditional 7+3 induction therapy.A multiinstitutional phase I dose-escalation study of alvocidib on days 1-3 followed by 7+3 (cytarabine 100 mg/m2/day i.v. infusion days 5-12 and daunorubicin 60 mg/m2 i.v. days 5-7) was performed in newly diagnosed AML ≤65 years. Core-binding factor AML was excluded.There was no MTD on this study; the recommended phase II dose of alvocidib was 30 mg/m2 i.v. over 30 minutes followed by 60 mg/m2 i.v. infusion over 4 hours. There was one dose-limiting toxicity of cytokine release syndrome. The most common grade ≥3 nonhematologic toxicities were diarrhea (44%) and tumor lysis syndrome (34%). Overall, 69% (22/32) of patients achieved complete remission (CR). In an exploratory cohort, eight of nine (89%) patients in complete remission had no measurable residual disease, as determined by a centralized flow cytometric assay. Clinical activity was seen in patients with secondary AML, AML with myelodysplastic syndrome-related changes, and a genomic signature of secondary AML (50%, 50%, and 92% CR rates, respectively).Alvocidib can be safely administered prior to 7+3 induction with encouraging clinical activity. These findings warrant further investigation of alvocidib combinations in newly diagnosed AML. This study was registered at clinicaltrials.gov identifier NCT03298984.
病原性大腸菌における重複グルタミン酸デカルボキシラーゼ遺伝子(gadAおよびgadB)間の最近の遺伝子変換 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: M Bergholz Teresa, L Tarr Cheryl, M Christensen Lisa, J Betting David, S Whittam Thomas
Journal: Molecular Biology and Evolution (2007)
Standardized definitions for evaluation of heart failure therapies: scientific expert panel from the Heart Failure Collaboratory and Academic Research Consortium
Authors: William T. Abraham, Mitchell A. Psotka, Mona Fiuzat, Gerasimos Filippatos, JoAnn Lindenfeld, Roxana Mehran, Amrut V. Ambardekar, Peter E. Carson, Richard Jacob, James L. Januzzi, Marvin A. Konstam, Mitchell W. Krucoff, Eldrin F. Lewis, Jonathan P. Piccini, Scott D. Solomon, Norman Stockbridge, John R. Teerlink, Ellis F. Unger, Emily P. Zeitler, Stefan D. Anker, Christopher M. O'Connor
Journal: European Journal of Heart Failure (2020)
Transcriptome-directed analysis for Mendelian disease diagnosis overcomes limitations of conventional genomic testing
Authors: David R. Murdock, Hongzheng Dai, Lindsay C. Burrage, Jill A. Rosenfeld, Shamika Ketkar, Michaela F. Müller, Vicente A. Yépez, Julien Gagneur, Pengfei Liu, Shan Chen, Mahim Jain, Gladys Zapata, Carlos A. Bacino, Hsiao-Tuan Chao, Paolo Moretti, William J. Craigen, Neil A. Hanchard, Brendan Lee
Journal: Journal of Clinical Investigation (2020)

BACKGROUND. Transcriptome sequencing (RNA-seq) improves diagnostic rates in individuals with suspected Mendelian conditions to varying degrees, primarily by directing the prioritization of candidate DNA variants identified on exome or genome sequencing (ES/GS). Here we implemented an RNA-seq–guided method to diagnose individuals across a wide range of ages and clinical phenotypes.
Assessment of Year-to-Year Patient-Specific Comorbid Conditions Reported in the Medicare Chronic Conditions Data Warehouse
Authors: William B. Weeks, Grace Huynh, Stacey Y. Cao, Jeremy Smith, James N. Weinstein
Journal: JAMA Network Open (2020)

year for anemia) and conditions with high cure rates (eg, hip and pelvic fracture). MethodsThe Solutions IRB institutional review board and the Centers for Medicare & Medicaid Services approved this cross-sectional study.They determined that informed