tbuckley/cabot-search huggingface dataset:
Abstract 12737: Sex and Race/Ethnic Disparities in the Use of High Potency Statins for Patients With Atherosclerotic Cardiovascular Disease
Authors: Fatima Rodriguez, Shoutzu Lin, Paul A Heidenreich
Journal: Circulation (2015)

Background: The November 2013 AHA/ACC prevention guidelines recommend the use of a fixed dose high potency statin (HPS) for patients with established atherosclerotic cardiovascular disease (ASCVD), irrespective of low-density lipoprotein cholesterol levels. We sought to determine how these guidelines are being adopted at the Veterans Affairs (VA) Health System and identify treatment gaps in patient groups. Methods: We examined administrative data from the VA 6 months prior to the index dates of 4/1/2013 and 4/1/2014 to identify patients with at least one outpatient visit for a diagnosis of established ASCVD, defined as coronary heart disease, cerebrovascular disease, or peripheral arterial disease. Statin use was assessed 6 months following the index date, and HPS was defined as atorvastatin 40mg or 80mg, rosuvasatin 20mg or 40mg, and simvastatin 80mg. Patient and facility-level predictors of statin use for secondary prevention were analyzed using multivariate logistic regressions. Results: Our study sample included 507,072 and 489,754 eligible adults with established ASCVD, in 4/1/2013 and 4/1/2014, respectively. The sample consisted of approximately 190,035 (2%) women and 200,461 (19%) non-white patients. HPS use was lowest in Hispanics and Native Americans, though all groups showed an increase over time (Figure 1). After adjustment for clinical and facility characteristics, there was a 40% increase in the use of HPS during the study period [OR=1.4; 95%CI (1.39-1.42)]. However, the racial differences shown in Figure 1 persisted and women were less likely to receive HPS than men (Odds Ratios [OR]=0.85; 95% CI 0.83-0.87). Conclusion: HPS use has increased following release of the ACC/AHA prevention guideline in the VA, though racial and gender disparities persist. Our findings highlight the continued need for targeted efforts to increase HPS use for women and certain minority groups.
Patient being charged £54 000 for radiotherapy wins legal aid to challenge rules
Authors: Clare Dyer
Journal: BMJ (2018)

A homeless patient with cancer who has lived in the UK for 44 years has been granted legal aid to explore a possible High Court challenge to a decision that he must pay the NHS £54 000 (€61 000; $75 000) upfront for radiotherapy unless he can prove that he has a legal right to live in the country.

Albert Thompson, 63, came to the UK from Jamaica in 1973 as a teenager to join his mother and has lived in London ever since. But his original Jamaican passport was lost years ago and he cannot prove that he has the right to UK residence.

Thompson, who is using a pseudonym in the media to preserve his privacy, had prostate surgery on the NHS in 2017. But access to free NHS treatment for immigrants has …
SINUS OF VALSALVA RUPTURE IN A PATIENT WITH A BICUSPID AORTIC VALVE
Authors: Jennifer Treece, Sowminya Arikapudi, Zia Ur Rahman, Tarvinder Gilotra, Vatsal Ladia, Kais Albalbissi, Terry Forrest, Harold Alison
Journal: Journal of the American College of Cardiology (2018)
Feasibility and safety of treating non-unions in tibia, femur and humerus with autologous, expanded, bone marrow-derived mesenchymal stromal cells associated with biphasic calcium phosphate biomaterials in a multicentric, non-comparative trial
Authors: Enrique Gómez-Barrena, Philippe Rosset, Florian Gebhard, Philippe Hernigou, Nicola Baldini, Helène Rouard, Luc Sensebé, Rosa M. Gonzalo-Daganzo, Rosaria Giordano, Norma Padilla-Eguiluz, Eduardo García-Rey, José Cordero-Ampuero, Juan Carlos Rubio-Suárez, Julien Stanovici, Christian Ehrnthaller, Markus Huber-Lang, Charles Henri Flouzat-Lachaniette, Nathalie Chevallier, Davide Maria Donati, Gabriela Ciapetti, Sandrine Fleury, Manuel-Nicolás Fernandez, José-Rafael Cabrera, Cristina Avendaño-Solá, Tiziana Montemurro, Carmen Panaitescu, Elena Veronesi, Markus Thomas Rojewski, Ramin Lotfi, Massimo Dominici, Hubert Schrezenmeier, Pierre Layrolle
Journal: Biomaterials (2018)

ORTHO-1 is a European, multicentric, first in human clinical trial to prove safety and feasibility after surgical implantation of commercially available biphasic calcium phosphate bioceramic granules associated during surgery with autologous mesenchymal stromal cells expanded from bone marrow (BM-hMSC) under good manufacturing practices, in patients with long bone pseudarthrosis.Twenty-eight patients with femur, tibia or humerus diaphyseal or metaphyso-diaphyseal non-unions were recruited and surgically treated in France, Germany, Italy and Spain with 100 or 200 million BM-hMSC/mL associated with 5-10 cc of bioceramic granules. Patients were followed up during one year. The investigational advanced therapy medicinal product (ATMP) was expanded under the same protocol in all four countries, and approved by each National Competent Authority.With safety as primary end-point, no severe adverse event was reported as related to the BM-hMSC. With feasibility as secondary end-point, the participating production centres manufactured the BM-hMSC as planned. The ATMP combined to the bioceramic was surgically delivered to the non-unions, and 26/28 treated patients were found radiologically healed at one year (3 out of 4 cortices with bone bridging).Safety and feasibility were clinically proven for surgical implantation of expanded autologous BM-hMSC with bioceramic.EU-FP7-HEALTH-2009, REBORNE Project (GA: 241876).
THE EFFECTIVENESS OF MICROBUBBLE-MEDIATED SONOTHROMBOLYSIS FOR INDUCING EARLY RECANALIZATION OF DIFFERENT CULPRIT CORONARY ARTERIES IN PATIENTS WITH ACUTE ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION
Authors: Wilson Mathias, Bruno G. Tavares, Miguel Osman Aguiar, Jeane Tsutsui, Hsu Chiang, Alexandre Soeiro, Mucio Oliveira, Jose Nicolau, Pedro Lemos, Bernardo Lopes, Carlos Rochitte, Erica Viana, João Sbano, Roberto Kalil-Filho, Thomas Porter
Journal: Journal of the American College of Cardiology (2018)
ELEVATED LEVELS OF THE NEUTROPHIL TO LYMPHOCYTE RATIO PREDICTS INCIDENCE OF MAJOR ADVERSE CARDIOVASCULAR EVENTS IN HIGH RISK PATIENTS: INSIGHTS FROM ACCELERATE
Authors: Adam J. Nelson, Stephen Nicholls, A. Lincoff, Venu Menon, Jeffrey Riesmeyer, Giacomo Ruotolo, Kathy Wolski, Ellen McErlean, Steven Nissen
Journal: Journal of the American College of Cardiology (2018)
Delivery of lethal dsRNAs in insect diets by branched amphiphilic peptide capsules
Authors: L.A. Avila, R. Chandrasekar, K.E. Wilkinson, J. Balthazor, M. Heerman, J. Bechard, S. Brown, Y. Park, S. Dhar, G.R. Reeck, J.M. Tomich
Journal: Journal of Controlled Release (2018)
Paper-based electrochemiluminescence sensor for highly sensitive detection of amyloid-β oligomerization: Toward potential diagnosis of Alzheimer's disease
Authors: Hongxing Liu, Xiaoming Zhou, Qi Shen, Da Xing
Journal: Theranostics (2018)

Development of a rapid and sensitive method for Aβ(1-42) aggregation detection is of great importance to overcome the limitations of conventional techniques.In this study, we developed a label-free paper-based electrochemiluminescence sensor for amyloid-β aggregation detection toward potential diagnosis of Alzheimer's disease (AD).The paper-based chip used in the system serves as a low-cost and disposable detection method.In this detection platform, the bonding of [Ru(phen) 2 dppz] 2+ to Aβ(1-42) aggregates results in enhanced electrochemiluminescence due to the change in the polarity of the microenvironment when [Ru(phen) 2 dppz] 2+ intercalated into the β-sheets during oligomerization.The oligomerization process of Aβ(1-42) can be monitored in real time by the novel method, and as low as 100 pM equivalent monomer concentration of Aβ(1-42) could be detected simultaneously.In addition, the cerebrospinal fluid of transgenic AD model mice was tested by this method, which is highly consistent with genetic identification.In addition, we demonstrated that this detection platform could be a potential new method for the screening of Aβ(1-42) aggregation inhibitors, highlighting the practical application capacity of this platform.The platform is label free, low cost and sensitive.Therefore, the proposed platform holds great promise for the diagnosis of AD.
Generations differ in their approach to doctor revalidation, study finds
Authors: Abi Rimmer
Journal: BMJ (2014)

Doctors’ attitudes towards revalidation and their readiness for the process vary across generations, researchers have found.

Researchers from the Plymouth University Peninsula Schools of Medicine and Dentistry sought to gain insight into doctors’ views on revalidation.1 From September 2011 to March 2013 they recorded seven appraisals and carried out 18 follow-up interviews with the appraisers and those being assessed. The researchers also interviewed four responsible officers, a regional General Medical Council employer liaison officer, and a primary care revalidation administrative lead.2

They found …
RCGP announces rise in trainees’ membership fees and cuts to entrance exam costs
Authors: Abi Rimmer
Journal: BMJ (2015)

The Royal College of General Practitioners has increased the amount that trainees pay for membership but has cut the costs of its membership examination.

The changes will mean that trainees starting in August 2015 will pay £595.43 more for associates in training (AiT) membership. The college said this increase in cost would be “largely offset” by a reduction of £409 in the combined fees for the clinical skills assessment and the applied knowledge test. It currently costs trainees £1780 …
Abstract P4-04-14: Anti-tumor activity of elacestrant (RAD1901) in combination with alpelisib (BYL-719) in patient-derived xenograft models of ER+ breast cancer
Authors: B Sankaran, F Garner, G Hattersley, D Purandare, T Bihani
Journal: Cancer Research (2018)

Abstract Estrogen-receptor positive (ER+) breast cancers make up approximately 70% of all breast cancers diagnosed. While patients with ER+ breast cancer have a better prognosis than other subtypes of breast cancer, the majority of those with advanced metastatic disease will eventually relapse. This has been attributed, in part, to mutations in the ER gene that result in constitutive activation of ER and contribute to aromatase inhibitor treatment resistance. As a strategy to deliver a more durable response in this setting, the use of selective estrogen receptor degraders (SERDs) that target and inhibit both wild-type and mutant ER has gained widespread attention. Indeed, fulvestrant, the only approved SERD on the market, is currently used as a second-line therapy in the metastatic setting, however, the intramuscular route of administration and pharmacokinetic properties of fulvestrant have fueled the development of orally bioavailable SERDs. We have previously described elacestrant (RAD1901), a novel and orally bioavailable selective estrogen receptor degrader (SERD) as an inhibitor of ER+ breast cancer growth in preclinical models, including those that harbor ER mutations and those that are insensitive to fulvestrant. In addition to ER mutations, the activation of parallel oncogenic pathways can also drive endocrine resistance, with the PI3K/Akt/mTOR pathway chief among those driving growth and treatment resistance to endocrine therapy. Consistent with these above-mentioned findings, recent clinical strategies to treat advanced ER+ disease have involved combining SERDs with PI3K inhibitors. Alpelisib (BYL-719) is a PI3K-alpha specific inhibitor that is being developed in combination with endocrine agents for the treatment of ER+ breast cancer. Here, we examined the effect of elacestrant in combination with alpelisib, in two ER+ breast cancer PDX models (one harboring wild-type ER and one harboring a Y537S mutation in the ER gene). The combination of elacestrant (10mg/kg) and alpelisib (35mg/kg) was well tolerated and resulted in significant tumor growth inhibition in both PDX models. Interestingly, in the mutant ER PDX model, the combination resulted in significantly greater growth inhibition relative to either compound alone. These data suggest the dual inhibition of the ER and PI3K signaling pathways with elacestrant and alpelisib produces significant anti-tumor activity in clinically-relevant PDX models, including those harboring ER mutations. Citation Format: Sankaran B, Garner F, Hattersley G, Purandare D, Bihani T. Anti-tumor activity of elacestrant (RAD1901) in combination with alpelisib (BYL-719) in patient-derived xenograft models of ER+ breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-04-14.
Recruitment problems led foundation trust to take on GP patients
Authors: Abi Rimmer
Journal: BMJ (2015)

An NHS foundation trust has taken on the patients of a general practice in Derbyshire after the practice struggled to recruit GPs.

Chesterfield Royal Hospital NHS Foundation Trust, in the form of Royal Primary Care, will be responsible for providing GP services to all patients registered with the Holywell Medical Group in Chesterfield and Staveley from 15 May. Royal Primary Care has been commissioned to provide an emergency caretaker service until 31 March 2016.1

Nadine Kale, senior partner at the Holywell Medical Group, said, “The partners have been exploring ways of integrating care with other local healthcare providers for some time. However, ongoing difficulties to recruit health professionals, particularly GPs, and the financial pressures of having to use more locum doctors have driven this urgent change.”

She added, “This is the first integration of primary and secondary care in the north Derbyshire …
Government threatens to force through GMS changes for 2013-14
Authors: Caroline White
Journal: BMJ (2012)

The Department of Health has warned that it may impose its suggested changes to the terms and conditions of next year’s general practitioners’ general medical services (GMS) contract if agreement with the BMA cannot be reached.

Its intention, announced in a letter formally setting out the government’s proposals, comes after five months of negotiations with the BMA.

The move has infuriated the association, which has called into question the evidence on which some of the government’s proposals were based and the feasibility of their implementation.

Barbara Hakin, national managing director of commissioning development at the Department of Health, said that the decision had been prompted by the failure to reach an agreement with the BMA.

“This means that the Department of Health may need to vary the contract without agreement from …
What will happen in the United Kingdom when the 10 accession states join the European Union?
Authors: Rhona MacDonald
Journal: BMJ (2004)

<i>There are many opinions about what will happen when the 10 accession states join the European Union on 1 May. Amendments to the legislation are being made on almost a daily basis, so</i> Rhona MacDonald <i>sorts out the true facts, partial facts, and total fiction</i>
GMC to commission independent review into treatment of whistleblowers
Authors: Abi Rimmer
Journal: BMJ (2014)

The General Medical Council has said that it will commission an independent review of how it deals with whistleblowers.

Speaking to MPs on the parliamentary health select committee on Tuesday, Niall Dickson, the GMC’s chief executive, said that there were things the regulator needed to learn from its interactions with whistleblowers. The committee heard that the GMC’s confidential whistleblower helpline had received over 1000 calls since it opened in 2012 and had led to 71 fitness to practise cases being opened.1

The committee member Charlotte …
MAJOR ADVERSE CARDIAC EVENTS OF REVASCULARIZATION IN CHRONIC TOTAL CORONARY OCCLUSION COMPARED TO OPTIMAL MEDICAL THERAPY: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Saranapoom Klomjit, Wasawat Vutthikraivit, Pattara Rattanawong, Pakpoom Tantrachoti, Pavida Pachariyanon, Possawat Vutthikraivit, Awapa Prombandankul, Subhanudh Thavaraputta, Mohammad Ansari
Journal: Journal of the American College of Cardiology (2018)
Responsible officers expect their revalidation work to become more difficult
Authors: Caroline White
Journal: BMJ (2013)

Responsible officers in London expect to find revalidation more difficult next year as more challenging and costly issues emerge, a snapshot survey by health think tank the King’s Fund has revealed.1

Respondents to the survey said they believed that, in the second year of implementation of revalidation, they would have to deal with doctors who were less engaged with the scheme and who had more challenging performance concerns. They also said that they were worried about the amount of resource needed for the remediation of these practitioners.

The survey was commissioned by the NHS England (London region) revalidation team. It was designed to capture the experiences of the key players six months into the scheme, …
Collateral damage: Molecular aging and p16INK4a senescence protein in testicular cancer survivors treated with chemotherapy.
Authors: Maria Teresa Bourlon, Hugo Eduardo Velazquez, Luis Arturo Orozco Bello, Juan Hinojosa, Ricardo Rios-Corzo, Guadalupe Lima, Luis Llorente, Yemil Atisha-Fregoso
Journal: Journal of Clinical Oncology (2018)

548 Background: Cytotoxic chemotherapy can cure patients with advanced germ cell tumors. Nevertheless, cancer treatment may induce cellular senescence and accelerate molecular aging. The aging process implies an increase of cells expressing p16INK4a and changes in lymphocyte subpopulations. Our aim was to study the potential induction of premature immunosenescence in testicular cancer patients exposed to chemotherapy. Methods: Case-control study of testicular cancer survivors (TCS) treated with chemotherapy (≥3 BEP cycles, disease-free ≥ 3 months) matched by age with healthy controls. Peripheral blood mononuclear cells were isolated, and lymphocyte subpopulations were analyzed by flow cytometry. p16INK4a expression was measured using real-time polymerase chain reaction, and the 2 - ΔΔCt method was used for the p16INK4a expression analysis. Groups were compared with Mann-Whitney U test. Results are expressed as median (IQR) unless otherwise indicated. Results: We included 15 cases and 15 controls. Mean age 32.5 yo (24-54), mean time since last chemo 49.5 months (3-192). TCS had a lower percentage of CD3+ (62 (57-68) vs 72 (65-82) p = 0.026) and CD4+ (35 (27-41) vs 42 (38-53) p = 0.013) cells in total lymphocytes. TCS also had a lower % of naïve CD4+ (32 (15-44) vs 39 (32-55) p = 0.041), CD4+CD28+ (90 (85-97) vs 98 (95-99) p = 0.029) and CD8+ naïve (15 (8-26) vs 27 (22-42) p = 0.023) cells. TCS had an increased % of memory CD4+ (18 (13-26) vs 9 (6-11) p = 0.001) and memory CD19+ B cells (76 (62-88) vs 70 (64-79) p = 0.004). The relative expression of p16INK4a in CD3+ cells was higher in TCS compared to controls (1.29±0.36 vs 0.85±0.54; p = 0.035). Conclusions: TCS showed an increase in the expression of the aging biomarker p16INK4a and a lymphocyte phenotype associated with immunosenescence; characterized by a decrease in naïve cells, and concomitant increment of memory and CD28- cells. This phenomenon is believed to contribute to the development of an immune risk profile in the elderly, associated with an increased rate of infections and a diminished effect of vaccines. This is the first time this finding is reported in TCS. Further studies are warranted to define the clinical implications of this alteration.
Abstract P6-05-04: mRNA expression of PTK6V1 and PTKV2 in human breast cancer
Authors: H El Hage Chehade, A Harvey, U Wazir, WG Jiang, K Mokbel
Journal: Cancer Research (2018)

Abstract BACKGROUND: Protein tyrosine kinase 6 (PTK6) is an intracellular protein that is upregulated in several human cancers and its localization to the plasma-membrane facilitates its various oncogenic roles in breast cancer cell proliferation, survival, and migration. The full length protein (PTK6V1) and alternative splice variant (PTK6V2) seem to play different roles with the latter being negative regulator of the former. In this study, the level of mRNA expression of PTK6V1 and PTK6V2 were assessed in normal and malignant breast tissue using real time Q-PCR in a cohort of women with breast cancer and correlated to conventional clinico-pathological parameters and clinical outcome. MATERIALS AND METHODS: Breast cancer tissues (n = 127) and normal background tissues (n = 33) were collected immediately after excision during surgery. Following RNA extraction, reverse transcription was carried out and transcript levels were determined using real-time quantitative PCR and normalized against beta-actin expression. Transcript levels within the breast cancer specimens were compared to the normal background tissues and analysed against TNM stage, nodal involvement, tumour grade and clinical outcome over a 10 year follow-up period. RESULTS: The median copy number of transcripts of PTK6V1 were higher in malignant compared with normal breast tissue (23 vs.7) and overall increased with advancing tumour stage (374 vs. 13 for TNM3 vs. TNM1 respectively p=0.019 and 374 vs.23 for TNM3 vs. TNM2 p=0.0244). however these associations did reach statistical significance. PTK6V1 levels were associated with oestrogen receptor (ER) positivity (p = 0.061). The transcript levels were significantly higher in patients who developed recurrence (p=0.03) or died of breast cancer (p=0.003). PTK6V2 transcript levels were generally higher in normal breast tissue than in malignant tissues and decreased with increasing tumour stage and grade however these associations did not reach stastical significance. After a median follow up of 10 years, there was a trend for higher PTK6V2 expression to be associated with longer overall survival (OS) and disease free survival (DFS). PTK6V2/PTK6V1 ratio was a significant predictor of OS. Conclusions Our observations suggest that the two variants of PTK6 play opposing roles in mammary oncogenesis. These findings could have prognostic and therapeutic implications. Citation Format: El Hage Chehade H, Harvey A, Wazir U, Jiang WG, Mokbel K. mRNA expression of PTK6V1 and PTKV2 in human breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-05-04.