tbuckley/cabot-search huggingface dataset:
The New NHS: commentaries on the white paper: From command economy to demand management (Financing the NHS)
Authors: C. Ham
Journal: BMJ (1998)

The white paper sets out a bold and imaginative vision for the organisation and provision of health care. The unanswered question is whether the money will be available to turn this vision into reality.

Taking the optimistic view-the view set out in the white paper-there is no reason to believe those who argue that the NHS will be unable to cope with the demands of increasing public expectations, medical advances, and an aging population. On this reading, the proposals for improving clinical effectiveness and reducing unnecessary bureaucracy will enable the NHS to accommodate future pressures without sacrificing its commitment to universality and comprehensiveness. Moreover, by aligning clinical and financial responsibility, the government's plans will empower doctors and other health care professionals to improve services from the patient's perspective, particularly by reducing variations in performance.

Taking the pessimistic view, there …
Chronic Urticaria as a Manifestation of Necrotizing Venulitis
Authors: Nicholas Arthur Soter
Journal: New England Journal of Medicine (1977)

In a group of patients with a syndrome consisting of recurrent episodes of urticaria, arthralgia, abdominal pain, and (rarely) glomerulonephritis, examination of skin biopsy specimens showed necrotizing venulitis. An elevated erythrocyte sedimentation rate was the most common laboratory abnormality. Analyses of serum immunoglobulins revealed random abnormalities of immunoglobulin levels, and assessment of the complement system showed two groups of patients--some with hypocomplementemia and others with a normal complement system. In those with hypocomplementemia, there were low levels of C1q, C4 and, occasionally, C3, compatible with activation of the classic complement pathway. Although the cause of this syndrome is unknown, the complement profiles suggest that more than one mechanism of vascular damage may be operative.
Abstract 885: Human organic cation transporter 1 (hOCT1) as a mediator of bendamustine cytotoxic action.
Authors: Cristina Arimany-Nardi, Arnau Montraveta, Eriong Lee-Vergés, Hermann Koepsell, Dolors Colomer, Marçal Pastor-Anglada
Journal: Cancer Research (2013)

Abstract Bendamustine hydrochloride is a cytotoxic agent that encompasses structural features of alkylating and nucleoside-derived drugs. This drug is currently used in the treatment of several haemotological malignancies; among them Chronic Lymphocytic Leukemia (CLL). CLL is the most common leukemia in Western countries and is characterized by the accumulation of monoclonal CD5+ B cells in the blood, bone marrow, lymph nodes, spleen and other organs. The pathways facilitating the uptake of bendamustine hydrochloride into target cells still remain poorly understood. Here we have addressed this issue by monitoring the interaction of the drug with selected plasma membrane transporter candidates, which might be relevant to bendamustine pharmacokinetics and pharmacodynamics. We have used a panel of HEK293 cells stably expressing selected drug transporter proteins to prove that bendamustine is able to interact with human Organic Cation Transporter 1 (hOCT1) with a Ki of 140+/-10 μM, as deduced from cis-inhibition studies using tritiated 1-methyl-4-phenylpyridinium (MPP+) as hOCT model substrate. Genetic variants known to modify substrate/transporter interactions, some of them with high allelic frequency in humans, were also tested and, in particular, hOCT1M420Del showed a significant decrease in its affinity for the drug (Ki value 234+/-24 μM, p&amp;lt;0.05 vs the wild type transporter). The whole panel of hOCT1 and hOCT1 allelic variants were also tested for bendamustine-induced cytotoxicity and data consistent with bendamustine being a hOCT1 substrate were obtained. This was based upon the finding that hOCT1 expression triggered increased sensitivity to the drug and variants known to decrease drug-transporter affinity interactions were also shown to induce resistance. hOCT1 is expressed in CLL cells and genotyping of a cohort of 125 CLL patients is now allowing the analysis of the relationships between particular genetic variants and ex vivo bendamustine-induced cytotoxicity, thus opening the possibility that hOCT1 genotyping might be a useful tool in optimizing bendamustine-based therapies. Citation Format: Cristina Arimany-Nardi, Arnau Montraveta, Eriong Lee-Vergés, Hermann Koepsell, Dolors Colomer, Marçal Pastor-Anglada. Human organic cation transporter 1 (hOCT1) as a mediator of bendamustine cytotoxic action. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 885. doi:10.1158/1538-7445.AM2013-885
Intracoronary Gene Transfer of Adenylyl Cyclase 6 in Patients With Heart Failure
Authors: H. Kirk Hammond, William F. Penny, Jay H. Traverse, Timothy D. Henry, Matthew W. Watkins, Clyde W. Yancy, Ranya N. Sweis, Eric D. Adler, Amit N. Patel, David R. Murray, Robert S. Ross, Valmik Bhargava, Alan Maisel, Denise D. Barnard, N. Chin Lai, Nancy D. Dalton, Martin L. Lee, Sanjiv M. Narayan, Daniel G. Blanchard, Mei Hua Gao
Journal: JAMA Cardiology (2016)

Gene transfer has rarely been tested in randomized clinical trials.
Abstract 5285: PERK regulates autophagy and survival of luminal cells during mammary acinar morphogenesis
Authors: Alvaro Avivar-Valderas
Journal: Cancer Research (2010)

Abstract During normal mammary gland development both alveoli and lactiferous ducts develop a hollow lumen. Integrin-mediated cell attachment to the extracellular matrix (ECM) is crucial for proper growth and survival of mammary epithelial cells. Improper engagement to the surrounding ECM lead to the adhesion-dependent programmed cell death, or anoikis. However, in early breast cancer these hollow ducts become filled with anoikis-resistant cells, a hallmark of ductal carcinoma in situ (DCIS). The endoplasmic reticulum (ER) kinase PERK is a critical mediator of the translational repression during ER stress and is activated in matrix-deprived cells. Novel findings showed that ECM detachment robustly induces autophagy which transiently promote survival of luminal cells. Autophagy is a tightly regulated anabolic pro-survival process but if not reversed can ultimately lead to cell death. ER stress signaling and in particular PERK can activate autophagy. Furthermore, autophagy has been proposed as a mechanism to enhance the survival of early transformed cells lacking proper ECM contact. Using constitutive inhibition of PERK, we previously found that in ECM bound cells this kinase has an anti-proliferative function. However, this strategy precluded us from testing the precise regulation of PERK during lumen formation. Using MCF10A-Fv2E-PERK cells, where PERK phosphorylation is induced by the divalent molecule AP20187 (AP), we have now found that PERK promotes survival of intraluminal cells via autophagy. During mammary acinar morphogenesis PERK phosphorylation becomes detectable by day 4, peaks at day 6 and after day 8 it is extinguished. This coincided with the timing of autophagy induction in luminal cells. AP-mediated activation of PERK in Fv2E-PERK 3D cultures beyond day 8, induced ATG7 and Beclin1 expression, suggesting that accumulation of luminal cells is linked to autophagy. PERK induction of autophagy might block apoptosis because AP treatment resulted in a downregulation of BimEL expression and an overall reduction in the percentage of apoptotic cells. Moreover, mechanistic analysis revealed that PERK induction of autophagy is dependent on mTOR-&amp;gt;p70S6K signaling inhibition. We propose that PERK mediated inhibition of mTOR protects basement membrane detached cells from apoptosis via autophagy allowing for proper morphogenesis. We conclude that PERK activation in luminal cells leads to increased survival and luminal cell accumulation. This is associated with increased autophagy gene expression/processing and reduced expression of the pro-apoptotic factor BimEL. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5285.
Doctors must help explain need for NHS changes, says NHS Confederation
Authors: Z. Kmietowicz
Journal: BMJ (2012)

Doctors should take a lead in explaining to patients why major changes are needed to the health service in England to make it truly modern and sustainable, the head of the body that represents NHS organisations has said.

Those changes included the closure of some hospital units, not necessarily to save money but to improve the quality of care by concentrating specialist services in fewer centres, said Mike Farrar, chief executive of the NHS Confederation, the membership body for organisations that provide or commission NHS services. Another major change was to boost primary, community, and social services to enable more people to be treated at or …
AB0631 Multicenter retrospective analysis of effectiveness and safety of rituximab in korean patients with refractory systemic lupus erythematosus
Authors: S.-Y. Bang, S.-C. Bae, Y.-B. Joo, C.K. Lee, Y.M. Kang, H.A. Kim, C.-H. Suh, W.T. Chung, Y.-B. Park, J.-Y. Choe, T.-J. Kim, Y.-W. Park, D.-H. Yoo, H.-S. Lee
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Although two randomized placebo-controlled trials of rituximab (RTX) in systemic lupus erythematosus (SLE) failed to meet the primary efficacy end point, clinicians continue to use RTX off-label for refractory cases to current treatments. <h3>Objectives</h3> We evaluate the effectiveness and safety of rituximab for refractory SLE patients in Korea. <h3>Methods</h3> We retrospectively analyzed data of SLE patients treated with RTX which were obtained from eight tertiary rheumatologic clinics in Korea. <h3>Results</h3> The total of 39 SLE patients treated with RTX was recruited. They were composed of lupus nephritis 43.6%, hematologic 33.3%, arthritis 7.8%, myositis 7.8%, vasculitis 5.1%, and enteritis 2.6%. All patients had poorly responded to at least one (mean number of immunosuppressive agents, 2.5±1.1) conventional immunosuppressive treatments(cyclophosphamide 43.6%, mycophenolate mofetil 48.7%, azathiopurine 33.3%, and other drugs) before RTX therapy. Clinical improvements (complete remission or partial remission) occurred in 65%, 90%, 100%, 67%, and 67% of patients with renal, hematologic, arthritis, myositis, and other manifestations at 6 month after RTX, respectively. The SLEDAI score was significantly decreased from 10.8±7.1 at baseline to 6.7±4.0 at 6 month, 6.2±4.1 at 12 month, 5.5±3.6 at 24 month, and 6.2±4.3 at 36 month after RTX (p&lt;0.05). Among 28 clinical responders, 4 patients experienced a relapse of disease at 25±4 months. After retreatment with RTX, all these relapsed patients showed the response at 6 month. Infections were noted in 3 patients (7.7%). Fiqure 1. Response to 6 month after RTX treatment in refractory patients with SLE <h3>Conclusions</h3> Our multicenter retrospective analysis suggested that RTX could be effective and relatively safe therapeutic option in patients with severe refractory SLE until new novel B cell depletion therapy is available. <h3>Disclosure of Interest</h3> None Declared
Elevated MDP Activity in the Spleen Due to Fungal Infection
Authors: Ion Codreanu, Wichana Chamroonrat, Gang Cheng, Sabah Servaes, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2011)

Bone scintigraphic imaging using Tc-99m-methylene diphosphonate (MDP) is one of the most common nuclear medicine procedures. Although MDP can accumulate not only in osseous but also in soft tissue, increased MDP activity in the spleen is relatively uncommon. A 3-year-old girl with recurrent meduloblastoma underwent bone scintigraphy to evaluate for potential osteomyelitis and bone metastases. The images demonstrated increased MDP activity in the spleen in both early blood pool and 3-hour delayed images, which was due to Candida albicans infection.
P2-12-02: Correlation between BMI and Clinical Outcome of Patients with Early Stage HER2+ Breast Cancer from the N9831 Clinical Trial.
Authors: JA Crozier, A Moreno-Aspitia, KV Ballman, S Martino, LA Kutteh, NE Davidson, PA Kaufman, EA Perez
Journal: Cancer Research (2011)

Abstract Background Obesity, as defined by body mass index (BMI), has been associated with increased recurrence rate, shorter DFS and increased death rates due to breast cancer (BC). Most of the studies to date have examined the relationship of BMI and DFS in patients with hormone receptor positive disease. To our knowledge, BMI and its relationship with outcome in early stage HER2 positive breast cancer has not previously been examined. The N9831 is a large phase III trial testing the role of trastuzumab in the adjuvant setting of high risk patients with early stage HER2+ BC. We hypothesized that the occurrence of overweight and obesity may correlate with outcome. Methods: This analysis presents BMI and its relation to tumor characteristics and DFS in patients (pts) enrolled in the N9831 clinical trial. Pts were categorized as normal weight, overweight or obese using the WHO BMI classification parameters of &amp;lt; 25%, 25–29% and ≥ 30% respectively. For patient characteristics, patients were grouped into non-obese (BMI&amp;lt; 30) and obese (≥ 30) cohorts. DFS was estimated by the Kaplan-Meier method. Comparisons between arms A (chemotherapy alone), B (chemotherapy plus sequential trastuzumab) and C (chemotherapy plus concurrent trastuzumab) were performed using the Cox proportional hazards model, stratified by BMI. Results: Analysis was completed on 3,017 eligible pts. Obese pts were more likely to be older and postmenopausal (p&amp;lt;0.0001 for both). There was no significant association between BMI and ER/PR status (p=0.07) or histologic tumor grade (p=0.33). Obese pts were found to have significantly larger tumors ≥ 2 cm (p=0.002) and more positive lymph nodes (p=0.02). There was no significant difference in DFS within each intrinsic arm (A, B and C) between the obese and non-obese pts at 3, 5 or 7 yrs of follow up. However, pts in the non-obese group had significantly improved DFS in arm B and C compared to arm A (p=0.001 and p&amp;lt;0.0001 respectively). Also obese pts in arm C had significantly improved DFS compared to obese pts in arm A (p=0.008). There was a trend of improved DFS in the obese group in arm B compared to arm A, but this was not statistically significant (p=0.09). Pts in the normal weight and overweight groups did significantly better in arm B (p=0.02 for both) and arm C (p=0.01 and p=0.002 respectively) compared to arm A. Conclusions: This analysis of data from the N9831 study confirms that obese pts with early stage HER2+ tumors have worse clinical outcome than pts with BMI &amp;lt; 30%. Adjuvant trastuzumab improved clinical outcome regardless of BMI. This study supports weight loss intervention for obese women with early stage HER2+ BC. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-12-02.
Abstract IA14: Genomic alterations dysregulate cancer genes by modulating microRNA activity
Authors: Hua-Sheng Chiu, Xuerui Yang, Andrea Califano, Pavel Sumazin
Journal: Cancer Research (2015)

Abstract microRNAs play key roles in cancer etiology, and recent evidence suggests that targets of the same microRNA programs are stoichiometrically coupled via a competitive endogenous RNA (ceRNA) mechanism. Consequently, aberrant expression of multiple targets of the same microRNA program dysregulate coupled ceRNA- oncogenes and tumor suppressors. We computationally inferred and experimentally validated that coordinated copy number and methylation alterations contribute to physiologically significant in-trans dysregulation of hundreds of coupled oncogenes and tumor suppressors in multiple tumor contexts. Both high-throughput perturbation assays and low-throughput mutational assays confirmed significant ceRNA-mediated regulation of cancer genes in eight tumor contexts, including ESR1 and APC in breast and colon cancer, respectively. Our analysis infers roles for previously uncharacterized genomic alterations and it suggests that ceRNA-mediated interactions account for a substantial fraction of cancer's missing genomic variability. Citation Format: Hua-Sheng Chiu, Xuerui Yang, Andrea Califano, Pavel Sumazin. Genomic alterations dysregulate cancer genes by modulating microRNA activity. [abstract]. In: Proceedings of the AACR Special Conference on Computational and Systems Biology of Cancer; Feb 8-11 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 2):Abstract nr IA14.
ECOENDOSCOPIA EN PANCREATITIS AGUDA BILIAR COMO PASO PREVIO A INDICACIÓN DE CPRE
Authors: S Maestro Antolin, R Castillo Trujillo, K De Jesús Geneux, A Germade Martínez, A Pérez-Millán, J Barcenilla Laguna, F Igea Arisqueta
Journal: Endoscopy (2012)

Introducción: La litiasis biliar supone un importante porcentaje en la etiología de las pancreatitis agudas. Se produce, fundamentalmente, por la migración de un cálculo a la vía biliar principal con la consiguiente obstrucción de la vía biliar y el conducto pancreático. Se sabe que, en la mayoría de los casos, el cálculo termina siendo expulsado de forma espontánea por lo que muchos pacientes no precisan la realización de técnicas invasivas para la extracción del cálculo. Sin embargo, se precisa de un método sensible que permita detectar claramente que pacientes tienen o no coledocolitiasis. Objetivos: Determinar el impacto de la ecoendoscopia previa a la indicación de C.P.R.E. en pancreatitis aguda de probable origen biliar. Material y métodos: Durante el año 2011 se seleccionaron pacientes con pancreatitis aguda leve-moderada de probable origen biliar para la realización de una ecoendoscopia independiente de las cifras de bilirrubina y la presencia o no de dilatación de la vía biliar (se descartaron aquellos con diagnóstico de coledocolitiasis en ecografía abdominal al ingreso). La ecoendoscopia se realizó con ecoendoscopio sectorial o radial (Pentax®). Resultados: Se recogieron finalmente 22 pacientes con pancreatitis aguda de probable origen biliar, con una edad media de 63,86 siendo hombres el 64% (edad media 63,5) y mujeres el 36% (edad media 64,30). La estancia media fue de 5,5días y se realizó la ecoendoscopia en una media de 4,68días. 4 pacientes (18%) presentaron cifras de bilirrubina por encima de 4mg/dl. Se encontró coledocolitiasis en 7 pacientes (31.8%), remitiéndose todos ellos para C.P.R.E. donde finalmente solo 5 de esos 7 presentaron coledocolitiasis (71%). Todos los pacientes sin hallazgos en la vía biliar principal en la ecoendoscopia, así como a los que se realizó CPRE fueron remitidos para la realización de colecistectomía que se realizó en un tiempo cuya mediana fue de 83,5días (97días para los hombres y 69días para las mujeres) No se demostró en el seguimiento coledocolitiasis en ningún paciente con ecoendoscopia negativa. En el tiempo entre el episodio de pancreatitis aguda y la colecistectomía re-ingresaron 4 pacientes (18%): 2 (9%) por colecistitis aguda y 2 (9%) por nuevo episodio de pancreatitis aguda. Conclusiones: 1. La ecoendoscopia es una técnica altamente sensible para la detección de coledocolitiasis en pancreatitis aguda de probable origen biliar lo cual permite evitar la realización de C.P.R.E. en aquellos pacientes con resultado negativo. 2. Si la colecistectomía se realiza en un tiempo no muy prolongado el porcentaje de reingresos por nueva pancreatitis es muy bajo. 3. Son necesarios estudios con más potencia para comprobar estos aspectos
The Physiology of Mind. An Interpretation Based on Biological, Morphological, Physical and Chemical Considerations.
Journal: JAMA (1925)

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SAT0099 Preferences of Patients with Spondyloarthritis for the Items of the ASAS Health Index: A Best Worst Scaling: Table 1.
Authors: U. Kiltz, M. Hiligsmann, D. van der Heijde, J. Braun, W. Taylor, A. Cieza, W. Maksymowych, A. Boonen
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The ASAS Health Index (ASAS HI) is a disease-specific questionnaire aiming at measurement of health in patients with spondyloarthritis (SpA) which has been developed by Assessment of SpondyloArthritis international Society (ASAS). The 17 items of the ASAS HI address aspects of pain, emotional functions, sleep, sexual functions, mobility, self-care and community life based on the International Classification of Functioning, Disability and Health (ICF). These items can serve as the starting point to develop a disease-specific utility instrument that will enable to calculate disease specific quality adjusted life-years. To construct such utility instrument, the development steps require that the number of items should be reduced to a more manageable number of items. This selection should be based on items, which are most essential to patient9s health and on items which are most preferred by patients. It is not know which aspects of health matter most to patients with SpA and also the knowledge about patient9s preferences is limited. <h3>Objectives</h3> To understand the relative importance of the different items of the ASAS HI for functioning and health of patients with SpA. <h3>Methods</h3> A best-worse experiment was conducted using a questionnaire in patients with SpA from 20 countries worldwide. Patients answered 17 choice tasks that were constructed using the Sawtooth software. In each task, patients were asked to choose the most important item and the least important from a set of four items about their functioning and health. The estimated hierarchical Bayes method was used to generate the mean relative importance score for each item. <h3>Results</h3> 206 patients (59.7% male, mean (SD) age 42.4 (13.9) years, mean (SD) BASDAI 3.8 (2.3)) with SpA completed the experiment. The five most important items are pain, sleep, standing, exhausting, and motivation to do anything that requires physical effort (table 1). Eight items address concepts which are less important for the patients: toileting, sexual relations, driving, contact with people, walking outdoors, concentration, washing hair, and be able to overcome difficulties. Four items addresses concepts, which showed intermediate results addressing concepts of running, frustration, traveling, and financial changes. Subgroup analysis regarding subgroups of SpA and European versus Non-European countries showed robust results among subgroups. <h3>Conclusions</h3> This study provides information on the relative importance for patients with SpA of the items of the ASAS HI that will be used for the development of a utility value for patienst with SpA. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2883