tbuckley/cabot-search huggingface dataset:
Confronting State Medicaid Drug Spending Pressures
Authors: Rachel E. Sachs, Julie M. Donohue, Stacie B. Dusetzina
Journal: JAMA (2020)

Confronting State Medicaid Drug Spending PressuresAcross the country, state Medicaid budgets are under increasing strain, driven by factors including the high and increasing prices of prescription drugs.Nearly 30% of state spending supports Medicaid programs, 1 and Medicaid programs spent more than $29 billion on prescription drugs in 2017 after accounting for manufacturer discounts.Perhaps most concerning is the increasing share of spending devoted to a few high-cost drugs.In 2017, drugs costing more than $1000 per claim represented just 1.2% of claims but accounted for 43.7% of all Medicaid drug spending, which is up from 31.1% in 2014. 2 These problems will become even more challenging in the next few months because the coronavirus disease 2019 (COVID-19) pandemic has exacerbated state budget crises through lower tax revenues and higher Medicaid enrollment for newly uninsured individuals in the US.However, federal laws and regulations around drug coverage and pricing may have unintentionally contributed to strained Medicaid budgets and access challenges for patients.One potentially large driver of drug spending pressure on state Medicaid budgets arises from the interaction between US Food and Drug Administration (FDA) regulations with the US Centers for Medicare & Medicaid Services (CMS) Medicaid Drug Rebate Program, which was established under federal law in 1990.The Medicaid Drug Rebate Program required state Medicaid programs that choose to cover prescription drugs (as all do today) essentially to cover all FDA-approved drugs, but it also required pharmaceutical companies to provide Medicaid with rebates for drugs sold under the program.Today, brand-name drug manufacturers must provide a minimum rebate of 23.1% of their drug's average manufacturer price or the difference between the average manufacturer price and the lowest price given to any commercial payer, whichever is greater.This arrangement helped ensure that states could provide access to medically necessary drugs for their Medicaid beneficiaries, while also somewhat insulating the safety net program's finances.Unlike other health insurers, Medicaid programs cannot control costs through strategies like steering beneficiaries to lower-cost drugs by requiring cost sharing for more expensive products.Challenges with this arrangement that guaranteed coverage of all drugs quickly emerged.In 1990, FDA approval for a new drug required the completion of clinical trials demonstrating that the product was safe and effective for its intended use.But in 1992, largely in response to the HIV/AIDS crisis, the FDA created an accelerated approval program in which drugs intended for the treatment of "serious or life-threatening illnesses" aiming to provide "improved therapeutic benefit compared to existing treatment" could obtain early approval on the basis of a surrogate end point rather than a true clinical end point.
Impact of corticosteroid therapy on the outcomes of hepatocellular carcinoma treated with immune checkpoint inhibitor therapy
Authors: David J Pinato, Ahmed Kaseb, Yinghong Wang, Anwaar Saeed, David Szafron, Tomi Jun, Sirish Dharmapuri, Abdul Rafeh Naqash, Mahvish Muzaffar, Musharraf Navaid, Uqba Khan, ChiehJu Lee, Anushi Bulumulle, Bo Yu, Sonal Paul, Petros Fessas, Neil Nimkar, Dominik Bettinger, Hannah Hildebrand, Tiziana Pressiani, Yehia I Abugabal, Nicola Personeni, Yi-Hsiang Huang, Jingky Lozano-Kuehne, Lorenza Rimassa, Celina Ang, Thomas U Marron
Journal: Journal for ImmunoTherapy of Cancer (2020)

The impact of corticosteroid therapy (CT) on efficacy of immune checkpoint inhibitors (ICI) is undefined in hepatocellular carcinoma (HCC). We evaluated whether CT administered at baseline (bCT) or concurrently with ICI (cCT) influences overall (OS), progression-free survival (PFS) and overall response rates (ORR) in 341 patients collected across 3 continents. Of 304 eligible patients, 78 (26%) received &gt; 10 mg prednisone equivalent daily either as bCT (n=14, 5%) or cCT (n=64, 21%). Indications for CT included procedure/prophylaxis (n=37, 47%), management of immune-related adverse event (n=27, 35%), cancer-related symptoms (n=8, 10%) or comorbidities (n=6, 8%). Neither overall CT, bCT nor cCT predicted for worse OS, PFS nor ORR in univariable and multivariable analyses (p&gt;0.05). CT for cancer-related indications predicted for shorter PFS (p&lt;0.001) and was associated with refractoriness to ICI (75% vs 33%, p=0.05) compared with cancer-unrelated indications. This is the first study to demonstrate that neither bCT nor cCT influence response and OS following ICI in HCC. Worse outcomes in CT recipients for cancer-related indications appear driven by the poor prognosis associated with symptomatic HCC.
Does load management using the acute:chronic workload ratio prevent health problems? A cluster randomised trial of 482 elite youth footballers of both sexes
Authors: Torstein Dalen-Lorentsen, John Bjørneboe, Benjamin Clarsen, Markus Vagle, Morten Wang Fagerland, Thor Einar Andersen
Journal: British Journal of Sports Medicine (2020)

Background The acute:chronic workload ratio (ACWR) is commonly used to manage training load in sports, particularly to reduce injury risk. However, despite its extensive application as a prevention intervention, the effectiveness of load management using ACWR has never been evaluated in an experimental study. Aim To evaluate the effectiveness of a load management intervention designed to reduce the prevalence of health problems among elite youth football players of both sexes. Methods We cluster-randomised 34 elite youth football teams (16 females, 18 males) to an intervention group (18 teams) and a control group (16 teams). Intervention group coaches planned all training based on published ACWR load management principles using a commercially available athlete management system for a complete 10-month season. Control group coaches continued to plan training as normal. The prevalence of health problems was measured monthly in both groups using the Oslo Sports Trauma Research Centre Questionnaire on Health Problems. Results The between-group difference in health problem prevalence (primary outcome) was 1.8%-points (−4.1 to 7.7 %-points; p=0.55) with no reduction in the likelihood of reporting a health problem in the intervention group (relative risk 1.01 (95% CI 0.91 to 1.12); p=0.84) compared with the control group. Conclusions We observed no between-group difference, suggesting that this specific load management intervention was not successful in preventing health problems in elite youth footballers. Trial registration number ISRCTN18177140 .
Quality indicators of colorectal cancer care in a public healthcare institution in Uruguay: Results from a retrospective population-based study.
Authors: Santiago Fontes, Mauricio Cuello, Ana Marín-Jiménez, Juan Carlos Sánchez, Megan Berry, Graciela Reyes, Nicolás Requena, Gabriel David Krygier
Journal: Journal of Clinical Oncology (2020)

234 Background: There is an urgent need to assess quality of cancer care in Latin America, especially amongst the most prevalent tumors, such as colorectal cancer. The main aim of this study was to assess adherence to previously validated quality indicators (QIs) for colorectal cancer in the context of a public healthcare provider in Uruguay. Methods: Data regarding all colorectal cancers registered between January 1, 2008 and December 31, 2019 at the National Cancer Institute of Montevideo was collected through retrospective analysis of medical records. We used 12 QIs (4 diagnostic, 7 treatment,1 surveillance) validated in previous publications. Each QI was analyzed as a proportion (%) and compared to target values with 95% confidence interval. Results: A total of 808 colorectal cancers were identified; only 10.1% were diagnosed by screening, 87% were diagnosed after reporting symptoms and 29.5% underwent emergency surgery. A complete preoperative colonoscopy was performed in 47% of patients, 64% had a CT-TAP scan and 63% of locally advanced rectal cancers had staging MRI prior to definitive treatment. Surgical resection with tumor free margins was obtained in 97% of cases, and for 68% at least 12 lymph nodes were examined. Neoadjuvant radiotherapy plus chemotherapy as first therapeutic strategy was implemented in 79% of rectal cancers. High risk stage II and III colon cancer received adjuvant chemotherapy within 16 weeks of surgery in 72,9% of cases. Postoperative follow up with CEA was registered in 97% of our series. Most patients ≤ 75 years of age with metastatic unresectable colorectal cancer at diagnosis underwent first-line chemotherapy or bio-chemotherapy. A low level of adherence was identified in micro-satellite and RAS status testing, 16 and 22 patients respectively. Conclusions: This study is a pioneer study in Latin America. The standardization of QI definition to achieve interregional comparative goals remains an unmet need.Our data indicates there is much to improve in early diagnosis, preoperative staging, neoadjuvant therapy and molecular testing. QI indicators in surgery and adjuvant chemotherapy prescription are similar to those reported in international studies.
Maintenance of Remission With Tofacitinib Therapy in Patients With Ulcerative Colitis
Authors: Jean-Frederic Colombel, Mark T. Osterman, Andrew J. Thorpe, Leonardo Salese, Chudy I. Nduaka, Haiying Zhang, Nervin Lawendy, Gary S. Friedman, Daniel Quirk, Chinyu Su, Walter Reinisch
Journal: Clinical Gastroenterology and Hepatology (2020)
Preclinical Comparison of the Blood–brain barrier Permeability of Osimertinib with Other EGFR TKIs
Authors: Nicola Colclough, Kan Chen, Peter Johnström, Nicole Strittmatter, Yumei Yan, Gail L. Wrigley, Magnus Schou, Richard Goodwin, Katarina Varnäs, Sally J. Adua, Minghui Zhao, Don X. Nguyen, Gareth Maglennon, Peter Barton, James Atkinson, Lin Zhang, Annika Janefeldt, Joanne Wilson, Aaron Smith, Akihiro Takano, Ryosuke Arakawa, Mikhail Kondrashov, Jonas Malmquist, Evgeny Revunov, Ana Vazquez-Romero, Mohammad Mahdi Moein, Albert D. Windhorst, Natasha A. Karp, M. Raymond V. Finlay, Richard A. Ward, James W.T. Yates, Paul D. Smith, Lars Farde, Zack Cheng, Darren A.E. Cross
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Osimertinib is a potent and selective EGFR tyrosine kinase inhibitor (EGFR-TKI) of both sensitizing and T790M resistance mutations. To treat metastatic brain disease, blood–brain barrier (BBB) permeability is considered desirable for increasing clinical efficacy. Experimental Design: We examined the level of brain penetration for 16 irreversible and reversible EGFR-TKIs using multiple in vitro and in vivo BBB preclinical models. Results: In vitro osimertinib was the weakest substrate for human BBB efflux transporters (efflux ratio 3.2). In vivo rat free brain to free plasma ratios (Kpuu) show osimertinib has the most BBB penetrance (0.21), compared with the other TKIs (Kpuu ≤ 0.12). PET imaging in Cynomolgus macaques demonstrated osimertinib was the only TKI among those tested to achieve significant brain penetrance (Cmax %ID 1.5, brain/blood Kp 2.6). Desorption electrospray ionization mass spectroscopy images of brains from mouse PC9 macrometastases models showed osimertinib readily distributes across both healthy brain and tumor tissue. Comparison of osimertinib with the poorly BBB penetrant afatinib in a mouse PC9 model of subclinical brain metastases showed only osimertinib has a significant effect on rate of brain tumor growth. Conclusions: These preclinical studies indicate that osimertinib can achieve significant exposure in the brain compared with the other EGFR-TKIs tested and supports the ongoing clinical evaluation of osimertinib for the treatment of EGFR-mutant brain metastasis. This work also demonstrates the link between low in vitro transporter efflux ratios and increased brain penetrance in vivo supporting the use of in vitro transporter assays as an early screen in drug discovery.
Genomic Adaptations to Salinity Resist Gene Flow in the Evolution of Floridian Watersnakes
Authors: Rhett M Rautsaw, Tristan D Schramer, Rachel Acuña, Lindsay N Arick, Mark DiMeo, Kathryn P Mercier, Michael Schrum, Andrew J Mason, Mark J Margres, Jason L Strickland, Christopher L Parkinson
Journal: Molecular Biology and Evolution (2020)

The migration-selection balance often governs the evolution of lineages, and speciation with gene flow is now considered common across the tree of life. Ecological speciation is a process that can facilitate divergence despite gene flow due to strong selective pressures caused by ecological differences; however, the exact traits under selection are often unknown. The transition from freshwater to saltwater habitats provides strong selection targeting traits with osmoregulatory function. Several lineages of North American watersnakes (Nerodia spp.) are known to occur in saltwater habitat and represent a useful system for studying speciation by providing an opportunity to investigate gene flow and evaluate how species boundaries are maintained or degraded. We use double digest restriction-site associated DNA sequencing to characterize the migration-selection balance and test for evidence of ecological divergence within the Nerodia fasciata-clarkii complex in Florida. We find evidence of high intraspecific gene flow with a pattern of isolation-by-distance underlying subspecific lineages. However, we identify genetic structure indicative of reduced gene flow between inland and coastal lineages suggesting divergence due to isolation-by-environment. This pattern is consistent with observed environmental differences where the amount of admixture decreases with increased salinity. Furthermore, we identify significantly enriched terms related to osmoregulatory function among a set of candidate loci, including several genes that have been previously implicated in adaptation to salinity stress. Collectively, our results demonstrate that ecological differences, likely driven by salinity, cause strong divergent selection which promotes divergence in the N. fasciata-clarkii complex despite significant gene flow.
Neuropsychiatric complications of covid-19
Authors: Matthew Butler, Thomas A Pollak, Alasdair G Rooney, Benedict D Michael, Timothy R Nicholson
Journal: BMJ (2020)

Viral infections of the respiratory tract can have multisystemic effects, including on the central nervous system (CNS), and thus may precipitate a spectrum of psychiatric and neurological disorders. 1Some patients with covid-19 are now known to develop various CNS abnormalities with potentially serious and long term consequences, including stroke and isolated psychiatric syndromes. 2As covid-19 cases rise again worldwide, it is timely to review what we know and don't know about the acute and chronic neuropsychiatric sequelae and their potential mechanisms.In laboratory studies, SARS-CoV-2 is neurotropic (replicating in neurons) and has the potential to enter the CNS via angiotensin converting enzyme 2 receptors in the olfactory bulb. 3 Whether this happens in clinical populations is unclear.Postmortem studies show evidence of cerebral inflammation, and neuroimaging studies detect leucoencephalopathy and microbleeds in critically ill patients. 4 While viral RNA is typically absent from the cerebrospinal fluid 5 and postmortem brain samples, 6 antibodies to SARS-CoV-2 have been identified in cerebrospinal fluid. 7 Other mechanisms causing CNS dysfunction include cytokine driven inflammatory responses 8 and wider systemic effects such as endotheliopathy, breakdown of the blood-brain barrier, 7 and clotting abnormalities. 6 Additional biological mechanisms, including autoimmunity, may be relevant to psychiatric disorders, as well as the psychological trauma of life threatening illness and pandemic related socioeconomic stressors.The relative contributions of these mechanisms to neuropsychiatric complications remain largely unknown.
Prolonged residence of an albumin–IL-4 fusion protein in secondary lymphoid organs ameliorates experimental autoimmune encephalomyelitis
Authors: Ako Ishihara, Jun Ishihara, Elyse A. Watkins, Andrew C. Tremain, Mindy Nguyen, Ani Solanki, Kiyomitsu Katsumata, Aslan Mansurov, Erica Budina, Aaron T. Alpar, Peyman Hosseinchi, Lea Maillat, Joseph W. Reda, Takahiro Kageyama, Melody A. Swartz, Eiji Yuba, Jeffrey A. Hubbell
Journal: Nature Biomedical Engineering (2020)
Active Living After Cancer: Converting a group physical activity intervention for cancer survivors to a virtual format in response to the coronavirus pandemic.
Authors: Karen Basen-Engquist, Yue Liao
Journal: Journal of Clinical Oncology (2020)

261 Background: Active Living After Cancer (ALAC) is an evidence-based group program to help cancer survivors improve their physical functioning and quality of life through increasing physical activity. It has enrolled over 800 cancer survivors in the Houston and El Paso areas. The program prioritizes serving minority and medically underserved survivors and is offered in both English and Spanish. As a result of the coronavirus pandemic we converted the program to a virtual format. Here we report preliminary data on the outcomes of the virtual program. Methods: ALAC teaches cognitive and behavioral skills for increasing physical activity to cancer survivors through 12 group sessions. We converted the group sessions to a virtual format using the Zoom platform. Group attendance was monitored by health educators teaching the program, and participants completed questionnaires and did a 30-sec sit-to-stand test before and after the program to assess outcomes (physical activity, quality of life, physical functioning, program satisfaction). We compared outcomes for the virtual groups to those of previous in-person groups. Results: Five classes with 32 participants were started as in-person groups and converted to virtual. The dropout rate was higher (37.5%) in the virtual groups, compared to in-person groups (23.1%). However, both in-person and virtual group participants showed similar increases in physical activity, physical functioning, physical quality of life, and had high satisfaction (see table). Conclusions: Preliminary data indicate that the virtual format is feasible and produces similar outcomes when compared to the in-person format, although drop-out is higher in the virtual format. Virtual group participants may experience fewer mental health benefits (although this could be due to the stress of the pandemic). Additional analyses will include current participants who are completing all sessions virtually. [Table: see text]
Correspondence to: ‘Combination of human umbilical cord mesenchymal (stromal) stem cell transplantation with IFN-γ treatment synergistically improves the clinical outcomes of patients with rheumatoid arthritis’
Authors: Kevin Sheng-Kai Ma, Li-Tzu Wang, Shin-Yi Tsai
Journal: Annals of the Rheumatic Diseases (2020)

We read with great interest the article by He et al , which the authors reported that mesenchymal stem cell (MSC) transplantation (MSCT) plus interferon-γ (IFN-γ) combination therapy may realise clinical efficacy featuring good or moderate EULAR responses in patients with rheumatoid arthritis (RA) who responded poorly to conventional therapeutics including disease-modifying antirheumatic drugs.1 MSC-based therapies have become novel therapeutic approaches for RA through immunomodulation, including the induction of T regulatory cells (Treg).2 We agree with the authors that IFN-γ-primed MSCs may bring about improved immunomodulation in vitro (as suggested in Figure 2 by He et al 1), and propose that the results based on studies in patients could be juxtaposed with further evidence on the protocol of IFN-γ treatment, serum levels of IFN-γ in patients and …
Identifying resources available to physicians for management of financial toxicity: A Fellow-driven QI initiative.
Authors: Katrina Fischer, Sidharth Anand, Anne M. Walling, Sarah Marie Larson, John Glaspy
Journal: Journal of Clinical Oncology (2020)

294 Background: Insufficient patient-physician cost communication stems in part from limited physician awareness of actionable interventions when cost issues arise. Oncologists report low awareness of resources to help patients with financial toxicity and often feel underprepared to discuss and navigate this issue. Methods: All oncology fellows (n = 19) at the University of California, Los Angeles were invited to participate in QI project during the fall of 2019. As part of the curriculum, fellows were individually paired with an experienced attending and asked to review a hypothetical case of financial toxicity. The case described an elderly widow on Medicare, living hours from the cancer center who was non-adherent to her oral cancer therapy due to high copays. Participants were asked to identify at least four financial toxicity risk factors in the case, and to identify resources and strategies that a physician could use help navigate her financial concerns. A cost-health literacy survey was administered at baseline and at the conclusion of the curriculum to evaluate the impact of the program. Results: Of 19 participants, 16 completed the case based scenario. Nine categories of risk factors were identified (63% of participants identified an insurance issue, 44% lack of social support, 44% drug cost, 50% fixed income, 50% distance from treatment center, 31% logistical transportation concern). Physician directed solutions were primarily focused on three categories: drug cost, insurance issue, and transportation concerns. Together, an institutional specific financial toxicity tip sheet was generated for further dispersal at the cancer center. After participation in the intervention, more fellows agreed/strongly agreed that they could help a patient experiencing financial toxicity (62% v 6%, p = 0.005). Conclusions: A focused intervention can increase awareness of resources and strategies available to physicians in the management of patient financial concerns, which may impact physician engagement with issues of financial toxicity. Standardized education programs to further educate physicians on financial toxicity management strategies is warranted.