tbuckley/cabot-search huggingface dataset:
Evidence Underlying Policy Proposals for Sustainable Anticancer Drug Prices
Authors: Nora Franzen, Valesca P. Retèl, Winnie Schats, Wim H. van Harten
Journal: JAMA Oncology (2020)

The financial consequences of high-expenditure innovative drugs and the association of these consequences with access to cancer treatment are substantial. With oncology being one of the major spending blocks of care and research, innovative policies are needed to secure the sustainability and accessibility of health care systems. Despite this strong interest, structured approaches are missing to date, and proposals are often based on opinion rather than fact.To evaluate an inventory of policies to reduce drug prices at market launch and analyze the quantitative evidence on which these policies are based.For this systematic review, a literature search of the Ovid MEDLINE, Embase, Business Source Premier, ABI/Inform, World Health Organization, and Organisation for Economic Co-operation and Development databases was conducted for articles published between January 1, 2001, and December 31, 2017. Publications that described proposed policies with a direct or obvious indirect association with pharmaceutical prices at market launch and with relevance to oncology and high-income countries were included. Evidence basis was assessed per article, and quantitative articles were categorized according to time and data use. Main price mechanisms and scored system disruptiveness per proposal were identified. Data were analyzed from January 1, 2018, to January 1, 2019.Of the 4775 articles screened, 80 were selected, and an inventory of 23 policies to reduce medicine prices was created. Proposals were diverse but mainly applied the strengthening of competition as an underlying mechanism to reduce drug prices. Of the 80 studies, 23 used quantitative models, but existing evidence was insufficient to deduce price effects, especially considering system disruptiveness. The available evidence was used to identify promising proposals for which testing may be beneficial: transparency, delinkage, 2-part pricing, public research, orphan drug reform, and public clinical trials.The findings suggest that despite the urgency of the search for proposals that lead to sustainable drug prices, careful and structured testing of proposals is needed because the implications for access to drug treatment can be substantial.
Avoiding ageism and promoting independence from reference equations in lung function testing of older adults
Authors: Eralda Hegendörfer, Jean-Marie Degryse
Journal: European Respiratory Journal (2020)

<b>Spirometry quality and interpretation in very old adults needs to be further researched, especially the use of FEV<sub>1</sub> expressions that are independent of reference equations/values</b>http://bit.ly/2R9vyW6
Football cannot restart soon during the COVID-19 emergency! A critical perspective from the Italian experience and a call for action
Authors: Alessandro Corsini, Gian Nicola Bisciotti, Cristiano Eirale, Piero Volpi
Journal: British Journal of Sports Medicine (2020)

In early 2020, the world is facing a global emergency called COVID-19 (coronavirus disease 2019). On 11 March 2020, the WHO has declared the ‘Pandemic state’ calling the governments to take ‘urgent and aggressive action’ to delay and mitigate the peak of infection.

The seriousness of the situation is evidenced by the extreme uncertainty of the measures taken by the governments of the various countries to stem the pandemic spread.

From 8 March 2020, the Italian Government implemented extraordinary measures to decrease the pathogen spread, targeting social distancing between individuals. The law focused on closing the commercial business, limiting the sporting activities and decreasing the opportunity for social gatherings. The most important issue has been the sharp increase in the number of people infected which is causing a significant increase in acute respiratory failure cases (severe acute respiratory syndrome coronavirus 2 (SARS-COV-2)) and acute respiratory distress syndrome requiring hospital admission and intensive care treatment. Contrary from what was thought at the beginning, young people are also affected by the disease and can develop the severe respiratory conditions mentioned above.

Initially, despite the outbreak phenomenon, professional sports were not stopped, and on 11 March 2020, the …
Oncogenic Genomic Alterations, Clinical Phenotypes, and Outcomes in Metastatic Castration-Sensitive Prostate Cancer
Authors: Konrad H. Stopsack, Subhiksha Nandakumar, Andreas G. Wibmer, Samuel Haywood, Emily S. Weg, Ethan S. Barnett, Chloe J. Kim, Emily A. Carbone, Samantha E. Vasselman, Bastien Nguyen, Melanie A. Hullings, Howard I. Scher, Michael J. Morris, David B. Solit, Nikolaus Schultz, Philip W. Kantoff, Wassim Abida
Journal: Clinical Cancer Research (2020)

The genomic underpinning of clinical phenotypes and outcomes in metastatic castration-sensitive prostate cancer is unclear.
18F-PSMA 1007 in Suspected Renal Cell Carcinoma
Authors: Fahad Marafi, Arun Sasikumar, Abdullatif Al-Terki, Mahmoud Alfeeli
Journal: Clinical Nuclear Medicine (2020)

Abstract A 60-year-old man with suspected right renal cell carcinoma underwent 18 F-FDG PET/CT and 18 F prostate-specific membrane antigen (PSMA) 1007 PET/CT scan. Compared with the 18 F-FDG PET/CT scan, 18 F-PSMA 1007 PET/CT showed intense tracer concentration in the primary tumor in the right kidney and intense tracer concentration consistently in all lung nodules. Unlike noted in previous pilot studies with 68 Ga-PSMA, we observed that the primary renal tumor also showed intense tracer avidity with 18 F-PSMA 1007. 18 F-PSMA 1007 PET/CT may provide preoperative insight into possible etiology, histopathological probability of tumor type, staging information, and theranostic potentials in evaluation of suspected renal cell carcinoma.
Don’t forget chronic lung and immune conditions during covid-19, says WHO
Authors: Jacqui Thornton
Journal: BMJ (2020)

The World Health Organization has called on the global community to continue efforts to tackle longstanding health problems during outbreaks like covid-19 as it published new guidance on tuberculosis (TB) prevention.

Speaking on world TB day, WHO director general Tedros Adhanom Ghebreyesus said covid-19 highlighted just how vulnerable people with lung diseases and weakened immune systems can be.

But he said that programmes already in place to combat TB and other major infectious diseases can be leveraged to make the response to covid-19 more effective and rapid.

The new consolidated WHO guidance recommends scaling up TB preventive treatment among populations at highest risk, including household contacts of TB patients, …
Abstract ES2-2: Evolving opportunities to personalize radiation decisions - Guiding decisions to omit radiation after breast conserving surgery for invasive breast cancer
Authors: C Speers
Journal: Cancer Research (2020)

Abstract Much as the development of molecularly based signatures (OncotypeDx®, MammaPrint®, ProSigna™, etc.) has revolutionized the decision-making process surrounding the need for adjuvant chemotherapy in women with early stage breast cancer, the development of prognostic and predictive signatures to determine the need and efficacy of radiation for women with breast cancer holds similar promise. While preliminary efforts to develop these signatures has been encouraging, much work remains in order to successfully translate these signatures into the clinic. In this educational session, we will review the current status of genomic-based signatures for radiation decision making. We will also review the barriers to clinical adoption and the molecularly stratified trials testing these signatures for treatment omission. Ultimately, for any of these tests to be translated into the clinic it will require demonstration of their accuracy and reproducibility as a test and perhaps more importantly, demonstration of clinical utility and an ability to improve outcomes for women with breast cancer. While not yet realized, the ongoing development of these signatures holds much promise as the field seeks to finally realize “personalized medicine” as it relates to radiation treatment for women with breast cancer. Citation Format: C Speers. Evolving opportunities to personalize radiation decisions - Guiding decisions to omit radiation after breast conserving surgery for invasive breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr ES2-2.
Immunogenicity and safety of influenza vaccination in cancer patients receiving checkpoint inhibitors targeting PD-1 or PD-L1
Authors: A. Bayle, M. Khettab, F. Lucibello, A.N. Chamseddine, V. Goldschmidt, A. Perret, S. Ropert, F. Scotté, P. Loulergue, O. Mir
Journal: Annals of Oncology (2020)
Telling me you don’t know is ok, but not explaining functional neurological disorder is not
Authors: Jan Coebergh, Kim Hearne, Tim Nicholson
Journal: BMJ (2020)

We were very pleased to hear from a patient about their illness journey and agree that, when appropriate, uncertainty should be acknowledged by healthcare professionals and communicated to patients and their carers.1 Two of us (JC, TN) run specialist clinics for functional neurological disorders and one of us (KH) is the chief executive officer of a related charity (FND Action). We agree that a diagnosis …
A Bold Response to the COVID-19 Pandemic
Authors: Howard Bauchner, Joshua Sharfstein
Journal: JAMA (2020)

Over the next few months it is likely that the coronavirus disease 2019 (COVID-19) pandemic that has surged in New York City, Seattle, New Orleans, and Detroit will move from city to city and state to state.After the initial peak, absent highly effective medical interventions, the US will likely experience outbreaks of lingering disease for months and potentially years to come.As the US enters the next phase of COVID-19, critical questions will involve the nation's capacity to respond to outbreaks, protect high-risk populations, and limit community spread.Because of inadequate and continued lack of testing for COVID-19, a depleted and overworked public health workforce, lack of sophisticated integrated public health and clinical health information technology, and substantial cultural issues, the US has yet to implement an effective disease control strategy.Rather, the US has moved quickly from focused isolation and quarantine at a large scale to mitigation, largely focused on a single approach-social distancing.The fundamental question is whether the US can build a more targeted response capability so that the country can return to work, school, and other normal activities.A key milestone is the fall of 2020.If the initial social distancing and perhaps warmer temperatures reduce the scale of the outbreak this summer, there is a major risk of a resurgence during the traditional season of respiratory viruses.As a possible approach to respond to this challenge, the US should consider suspending the first year of medical school for 1 year and giving the incoming 20 000 medical students the opportunity to join a national service program for public health.Hopefully the vast majority of students would participate.Such a bold approach may be needed to ensure that the US has an adequate response to the next wave of disease and does not enter a prolonged depression that will further adversely affect the health of its citizens.The program should begin at the start of July.Incoming medical students should spend the month in online training on infectious disease epidemiology, infectious disease control in high-risk settings, and outbreak response.In August, they should deploy to state and local public health departments to enhance the capacity to support a test, trace, track, and quarantine strategy.The federal government should fund this project as a national service effort with a salary for the students and health coverage; it could be part of a larger initiative to engage other students, including those in nursing and public health, as well as out-of-work community members in the national response.Taking this bold step is justified on health and economic grounds.Today, localities have few resources available to
Chronic obstructive pulmonary disease and lung cancer incidence in never smokers: a cohort study
Authors: Hye Yun Park, Danbee Kang, Sun Hye Shin, Kwang-Ha Yoo, Chin Kook Rhee, Gee Young Suh, Hojoong Kim, Young Mog Shim, Eliseo Guallar, Juhee Cho, O Jung Kwon
Journal: Thorax (2020)

There has been limited evidence for the association between chronic obstructive pulmonary disease (COPD) and the incidence of lung cancer among never smokers. We aimed to estimate the risk of lung cancer incidence in never smokers with COPD, and to compare it with the risk associated with smoking. This cohort study involved 338 548 subjects, 40 to 84 years of age with no history of lung cancer at baseline, enrolled in the National Health Insurance Service National Sample Cohort. During 2 355 005 person-years of follow-up (median follow-up 7.0 years), 1834 participants developed lung cancer. Compared with never smokers without COPD, the fully-adjusted hazard ratios (95% CI) for lung cancer in never smokers with COPD, ever smokers without COPD, and ever smokers with COPD were 2.67 (2.09 to 3.40), 1.97 (1.75 to 2.21), and 6.19 (5.04 to 7.61), respectively. In this large national cohort study, COPD was also a strong independent risk factor for lung cancer incidence in never smokers, implying that COPD patients are at high risk of lung cancer, irrespective of smoking status.
A planetary health perspective on COVID-19: a call for papers
Authors: Alastair Brown, Richard Horton
Journal: The Lancet (2020)

It is natural during the unfolding coronavirus disease 2019 (COVID-19) pandemic to focus on emergency response planning, including containment, treatment procedures, and vaccine development, and nobody would doubt the need for these measures. However, an emergency can also open a window of opportunity for reflection and learning. We live in increasingly global, interdependent, and environmentally constrained societies and the COVID-19 pandemic exemplifies these aspects of our world. We would therefore be wise to take a broad integrated perspective on this disease, the impacts of which are already spilling over into the realms of economics, international trade, politics, and inequality. Resilience planning needs to cope with these cascading impacts, and prevention efforts require a similarly wide lens to encompass ecosystems, wild animal disease surveillance, agricultural practices, eating habits, and cultural traditions and contexts. In other words, we need a planetary health perspective that cuts across traditional domains of knowledge, governance, and economic sectors to properly address the challenge posed by COVID-19. We welcome submissions on all aspects of the COVID-19 pandemic across the Lancet titles, but here we are calling for submissions to The Lancet and The Lancet Planetary Health. We particularly welcome interdisciplinary research that integrates across important knowledge domains to provide a fuller understanding of the causes and socioeconomic impacts of COVID-19, as well as public understanding and responses, the efficacy of management and prevention interventions, and approaches for the identification and prevention of future such events within the wider context of the Sustainable Development Goals. Submit your paper through our respective online systems and please mention in your cover letter that your submission is in response to this call for papers. We declare no competing interests.
Eculizumab: A Review in Neuromyelitis Optica Spectrum Disorder
Authors: James E. Frampton
Journal: Drugs (2020)

The terminal complement protein (C5) inhibitor eculizumab (Soliris®) is the first agent to be specifically approved in the EU, USA, Canada and Japan for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adults who are aquaporin-4 water channel autoantibody (AQP4-IgG) seropositive and (in the EU only) for those with a relapsing course of disease. In the phase III PREVENT trial, eculizumab significantly reduced the risk of adjudicated relapse relative to placebo in patients with AQP4-IgG-seropositive NMOSD, approximately a quarter of whom did not receive concomitant immunosuppressive therapies. The beneficial effect of eculizumab was seen across all patient subgroups analysed and was accompanied by improvements in neurological and functional disability assessments, as well as generic health-related quality of life measures; it was sustained through 4 years of treatment, according to combined data from the PREVENT trial and an interim analysis of its ongoing open-label extension study. The safety profile of eculizumab in AQP4-IgG-seropositive NMOSD was consistent with that seen for the drug in other approved indications. Thus, eculizumab provides an effective, generally well tolerated and approved treatment option for this rare, disabling and potentially life-threatening condition.
Hair follicle stem cell replication stress drives IFI16/STING-dependent inflammation in hidradenitis suppurativa
Authors: Cindy Orvain, Yea-Lih Lin, Francette Jean-Louis, Hakim Hocini, Barbara Hersant, Yamina Bennasser, Nicolas Ortonne, Claire Hotz, Pierre Wolkenstein, Michele Boniotto, Pascaline Tisserand, Cécile Lefebvre, Jean-Daniel Lelièvre, Monsef Benkirane, Philippe Pasero, Yves Lévy, Sophie Hüe
Journal: Journal of Clinical Investigation (2020)

Hidradenitis suppurativa (HS) is a chronic, relapsing, inflammatory skin disease. HS appears to be a primary abnormality in the pilosebaceous-apocrine unit. In this work, we characterized hair follicle stem cells (HFSCs) isolated from HS patients and more precisely the outer root sheath cells (ORSCs). We showed that hair follicle cells from HS patients had an increased number of proliferating progenitor cells and lost quiescent stem cells. Remarkably, we also showed that the progression of replication forks was altered in ORSCs from hair follicles of HS patients, leading to activation of the ATR/CHK1 pathway. These alterations were associated with an increased number of micronuclei and with the presence of cytoplasmic ssDNA, leading to the activation of the IFI16/STING pathway and the production of type I IFNs. This mechanistic analysis of the etiology of HS in the HFSC compartment establishes a formal link between genetic predisposition and skin inflammation observed in HS.
COVID-19 and the Heart
Authors: Akbarshakh Akhmerov, Eduardo Marbán
Journal: Circulation Research (2020)

Infection with the severe acute respiratory syndrome novel coronavirus produces a clinical syndrome known as 2019 novel coronavirus disease (COVID-19). When severe, COVID-19 is a systemic illness characterized by hyperinflammation, cytokine storm, and elevations of cardiac injury biomarkers. Here, we review what is known about the pathophysiology of COVID-19, its cardiovascular manifestations, and emerging therapeutic prospects. In this rapidly moving field, this review was comprehensive as of April 3, 2020.
Human airway epithelial cells express a functional IL‐5 receptor
Authors: Karina T. Barretto, Rebecca A. Brockman‐Schneider, Ine Kuipers, Sarmila Basnet, Yury A. Bochkov, Matthew C. Altman, Nizar N. Jarjour, James E. Gern, Stephane Esnault
Journal: Allergy (2020)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Genetically, Developmentally, and Clinically Distinct Cognitive Subtypes in Schizophrenia: A Tale of Three Trajectories
Authors: Kathryn E. Lewandowski
Journal: American Journal of Psychiatry (2020)

Cognitive impairment is a core symptom dimension in schizophrenia: it is common, often severe, and associated with functional impairment (1).Historically, cognitive impairment in schizophrenia has been thought to be a function of neurodevelopment starting well before illness onset.Studies across illness phases suggest that, at the group level, some degree of cognitive disruption is present prior to diagnosis, becoming more pronounced around the prodrome and first episode, and settling into a new, lower baseline by the time of established illness (2).However, substantial heterogeneity in cognitive presentation is well described (3, 4), creating challenges in characterizing cognition and linking cognitive symptoms to neurobiology and clinical outcomes.Given the marked variability in cognition after illness onset, it is likely that cognitive developmental trajectories are also highly heterogeneous.Recent cross-sectional studies of patients in different illness stages using estimates of premorbid and current cognitive functioning have identified empirically derived subgroups of patients with distinct cognitive trajectories (e.g., 5-7), suggesting that cognitive course in schizophrenia may not follow a unitary path.Different patterns of brain structure and connectivity have been associated with distinct cognitive subtypes and trajectories (5, 7-9), and evidence from two genetic association studies of cognitive subgroups found that genetic markers were differentially associated with cognitive profiles (10, 11).These findings suggest that variability in cognitive functioning may be leveraged to identify more homogeneous subgroups and trajectories reflecting distinct biological markers.The identification of genome-wide polygenic risk scores (PRSs) for a variety of constructs ranging from diagnostic classifications (e.g., schizophrenia, attention deficit hyperactivity disorder [ADHD]) to more dimensional features (e.g., cognition, education) based on very large samples has created a set of valuable tools for examination of genetic risk along specific constructs of interest and may provide key information about unique genetic contributions not only to illnesses themselves but to different pathophysiological processes that lead to them.To this end, the article by Dickinson and colleagues in this issue of the Journal (12) combines two novel approaches-empirical stratification of cognitive trajectories and examination of multiple polygenic risk indicators (schizophrenia, cognition, ADHD, and education)-to examine distinct cognitive pathways in schizophrenia that may be associated with unique combinations of genetic risk factors.
The Neural Basis of Escape Behavior in Vertebrates
Authors: Tiago Branco, Peter Redgrave
Journal: Annual Review of Neuroscience (2020)

Escape is one of the most studied animal behaviors, and there is a rich normative theory that links threat properties to evasive actions and their timing. The behavioral principles of escape are evolutionarily conserved and rely on elementary computational steps such as classifying sensory stimuli and executing appropriate movements. These are common building blocks of general adaptive behaviors. Here we consider the computational challenges required for escape behaviors to be implemented, discuss possible algorithmic solutions, and review some of the underlying neural circuits and mechanisms. We outline shared neural principles that can be implemented by evolutionarily ancient neural systems to generate escape behavior, to which cortical encephalization has been added to allow for increased sophistication and flexibility in responding to threat.