tbuckley/cabot-search huggingface dataset:
What does locality commissioning in Avon offer? Retrospective descriptive evaluation
Authors: C. E Hine, M. O Bachmann
Journal: BMJ (1997)

<h3>Abstract</h3> <b>Objective:</b> To describe the impact, direct costs of, and participants9 attitudes to the first two years and eight months of locality commissioning in Avon. <b>Design:</b> Retrospective description of programme. <b>Setting:</b> Thirteen localities in Avon Health Authority area, covering 982 000 population and 147 general practices. <b>Methods:</b> Postal questionnaire survey of 147 general practitioners (one per practice); interviews with and questionnaire survey of 13 lead general practitioners and 13 so called link staff from the health authority. <b>Main outcome measures:</b> Locality initiatives, perceived influence, general practitioners9 attitudes, management costs. <b>Results:</b> Twenty initiatives were identified that had changed services to patients, and another nine were planned. The commonest initiatives concerned primary mental health care (seven), nurse specialists for primary care of chronic diseases (three), referral and clinical practice guidelines (seven), and access to hospital outpatient departments (one, with two others planned). Localities were more likely to have influenced the authority, trust managers, and consultants than social services, community health councils, and voluntary organisations. Activity varied between localities, lead general practitioners estimating that 120/147 (82%) of practices had been involved in locality meetings (range 44-100% in different localities). The authority had spent 6 p per capita on running the scheme, and the total time used by general practitioners for locality commissioning was estimated at 1.5 whole time equivalents. <b>Conclusion:</b> Locality commissioning has selectively changed services with limited extra funding and without delegation of hospital and community health service budgets. General practitioners wanted more policy and financial support. Further development should be based on evidence of costs, benefits, and limitations of locality commissioning schemes. <h3>Key messages</h3> Locality commissioning proved feasible in one of the United Kingdom9s largest health districts Locality groups were selective in scope, emphasising primary mental health and chronic disease care, guidelines, and outpatient access Cooperation between general practices serving geographically defined populations was enhanced Costs of general practitioners9 participation were negligible, but some general practitioners contributed unpaid time Lead general practitioners were frustrated by the lack of clear management framework and political impetus
Alpha interferon treatment may prevent hepatocellular carcinoma in HCV-related liver cirrhosis
Authors: Giuseppe Mazzella, Esterita Accogli, Sandra Sottili, Davide Festi, Monica Orsini, Antonio Salzetta, Vieri Novelli, Antonio Cipolla, Carlo Fabbri, Alessandro Pezzoli, Enrico Roda
Journal: Journal of Hepatology (1996)
Phase II study of everolimus in patients with locally advanced or metastatic transitional cell carcinoma of the urothelial tract: clinical activity, molecular response, and biomarkers
Authors: E. Seront, S. Rottey, B. Sautois, J. Kerger, L.A. D'Hondt, V. Verschaeve, J.-L. Canon, C. Dopchie, J.M. Vandenbulcke, N. Whenham, J.C. Goeminne, M. Clausse, D. Verhoeven, P. Glorieux, S. Branders, P. Dupont, J. Schoonjans, O. Feron, J.-P. Machiels
Journal: Annals of Oncology (2012)
A randomised dose finding study of oral tacrolimus (FK506) therapy in refractory ulcerative colitis
Authors: H Ogata
Journal: Gut (2006)

Immunosuppressive therapy with intravenous ciclosporin is an alternative treatment option to total colectomy for patients with ulcerative colitis (UC), while the benefits of oral administration of tacrolimus are not well defined and are based on reports of several uncontrolled studies.Patients with refractory active UC were randomly assigned to a high trough concentration (10-15 ng/ml) group (HT group) (n = 21), low trough concentration (5-10 ng/ml) group (LT group) (n = 22), or placebo group (n = 20). Patients received an initial oral dose of 0.025 [DOSAGE ERROR CORRECTED] mg/kg tacrolimus or placebo twice daily. Efficacy was evaluated in 60 patients based on a disease activity index (DAI) score. Fifty eight patients had additional treatment with tacrolimus and were evaluated for efficacy in a 10 week open label extension.An improvement in DAI score (>or=4 points, all categories improved) was observed for 68.4% of cases in the HT group compared with 10.0% in the placebo group (p<0.001). In the HT group, 20.0% of patients had clinical remission and 78.9% had mucosal healing. In the open label extension, 55.2% of all patients had an improved DAI score at week 10. Mean dose of prednisolone was reduced from 19.7 mg/day at study entry to 7.8 mg/day at week 10. The incidence of side effects in the HT group was significantly higher than that of the placebo group (p = 0.043). The most common event was mild finger tremor.Our findings demonstrate dose dependent efficacy and safety of oral tacrolimus for remission-induction therapy of refractory UC. The optimal target range appears to be 10-15 ng/ml in terms of efficacy with two week therapy.
Incidence and prevalence of pregnancy-related heart disease
Authors: K. Sliwa, M. Bohm
Journal: Cardiovascular Research (2014)

Worldwide, the numbers of women who have a pre-existing cardiovascular disease or develop cardiac problems during pregnancy are increasing and, due to the lack of evidenced-based data, this provides challenges for the treating physician. Cardiovascular disease in pregnancy is a complex topic as women can present either pre- or post-partum, due to a pre-existing heart disease such as operated on or unoperated on congenital heart disease, valvular heart disease, chronic hypertension, or familial dilated cardiomyopathy. Women often present with symptoms and signs of acute heart failure. On the other hand, there are diseases which are directly related to pregnancy, such as hypertensive disorders of pregnancy and peripartum cardiomyopathy, or where pregnancy increases risk of a disease as, for example, the risk of myocardial infarction. These diseases can have long-term implications to the life of the affected women and their families. There is, in particular, a paucity of data from developing countries of this unique disease pattern and its presentations. This review summarizes the current knowledge of the incidence and prevalence of pregnancy-related cardiovascular disease in women presenting pre- or post-partum.
Measuring asthma control: a comparison of three classification systems
Authors: P. M. O'Byrne, H. K. Reddel, G. Eriksson, O. Ostlund, S. Peterson, M. R. Sears, C. Jenkins, M. Humbert, R. Buhl, T. W. Harrison, S. Quirce, E. D. Bateman
Journal: European Respiratory Journal (2010)

There are various ways to classify asthma control; however, no classification is universally accepted. This retrospective analysis compared asthma control as assessed by the Asthma Control Questionnaire (5-item version; ACQ-5), Global Initiative for Asthma (GINA) or Gaining Optimal Asthma Control (GOAL) study criteria. Pooled data at the final study week (n = 8,188) from three budesonide/formoterol maintenance and reliever therapy studies which measured ACQ-5 were stratified according to GINA or GOAL criteria and ACQ-5 score distribution. The percentages of patients with a controlled/partly controlled week (GINA), totally/well-controlled week (GOAL) and range of ACQ-5 cut-off points were compared. Patients with GINA controlled, partly controlled and uncontrolled asthma had mean ACQ-5 scores of 0.43, 0.75 and 1.62, respectively. Patients with GOAL totally controlled, well-controlled and uncontrolled asthma had ACQ-5 scores of 0.39, 0.78 and 1.63. The kappa measure of agreement was 0.80 for GINA and GOAL criteria, and 0.63 for GINA controlled/partly controlled and ACQ-5 &lt;1.00. ACQ-5 detected clinically important improvements in 49% of patients who, according to GINA criteria, remained uncontrolled at the end of the study. Asthma control measured by GINA or GOAL criteria provides similar results. GINA Controlled/Partly Controlled and GOAL Totally Controlled/Well-Controlled correspond to ACQ-5 &lt;1.00. The ACQ-5 is more responsive to change in a clinical trial setting than a categorical scale.
Does the Tertiary Gleason Pattern Influence the PSA Progression-Free Interval after Retropubic Radical Prostatectomy for Organ-Confined Prostate Cancer?
Authors: I.M. van Oort, B.M. Schout, L.A.L.M. Kiemeney, C.A. Hulsbergen, J.A. Witjes
Journal: European Urology (2005)
PharmGKB Update: II. CYP3A5, Cytochrome P450, Family 3, Subfamily A, Polypeptide 5
Authors: E. G. Schuetz, M. V. Relling, S. Kishi, W. Yang, S. Das, P. Chen, E. H. Cook, G. L. Rosner, C. H. Pui, J. G. Blanco, M. J. Edick, M. L. Hancock, N. J. Winick, T. Dervieux, M. D. Amylon, R. O. Bash, F. G. Behm, B. M. Camitta, S. C. Raimondi, B. C. Goh, S. C. Lee, L. Z. Wang, L. Fan, J. Y. Guo, J. Lamba, R. Lim, H. L. Lim, A. B. Ong, H. S. Lee, P. Kuehl, J. Zhang, Y. Lin, M. Assem, J. Schuetz, P. B. Watkins, A. Daly, S. A. Wrighton, S. D. Hall, P. Maurel, C. Brimer, K. Yasuda, R. Venkataramanan, S. Strom, K. Thummel, M. S. Boguski
Journal: Pharmacological Reviews (2004)

Category: Genotype PharmGKB Submission Numbers: PS113737, PS115406, PS114503, PS200420, PS201057, PS115245 <http://www.pharmgkb.org/do/serve?objId=PA131&objCls=Gene> Date of Submission: May 19, 2003 Project: Pharmacogenetics of Anticancer Agents, St. Jude Children's Research Hospital HGNC Symbol
Simultaneous laboratory-based comparison of ResMed Autoset with polysomnography in the diagnosis of sleep apnoea/hypopnoea syndrome
Authors: P Mayer, JC Meurice, F Philip-Joet, A Cornette, D Rakotonanahary, N Meslier, JL Pepin, P Levy, D Veale
Journal: European Respiratory Journal (1998)

ResMed Autoset (AS) is a simplified diagnosis system for obstructive sleep apnoea/hypopnoea syndrome (OSAS) based on the respiratory flow/time relationship by pressure variation measured through simple nasal prongs. A multicentre prospective trial was used to compare AS and polysomnography (PSG) for diagnosing 95 patients, with suspected OSAS. Physicians gave a pretest probability of the patient having OSAS. The apnoea/hypopnoea index (AHI) was compared between the two methods of diagnosis for the whole population and for subgroups according to the pretest probability. Twenty-four patients had AHI &lt; 15 events x h(-1) on PSG and 19 AHI 15-30, and 52 patients had AHI &gt; or = 30. Correlation between AHI assessed by AS and PSG was r=0.87 for total sleep time (TST), p&lt;0.0001. A Bland and Altman plot gave an agreement between the two methods of +/-40%. For a threshold of AHI &gt; or = 15 events x h(-1) to diagnose OSAS, AS has a sensitivity of 92%, specificity of 79%, positive predictive value of 93% and negative predictive value of 76%. With a pretest probability &gt; or = 80%, sensitivity and positive predictive value were 98 and 100% respectively. Of six false negative, four had a high pretest probability (&gt; 80%) or Epworth score &gt; or = 10. Using these parameters as a criterion for proceeding to PSG after a negative AS study would mean that two apnoeic patients (AHI 20 and 17 events x h(-1) by PSG) would escape detection. The Autoset is useful for the detection of obstructive sleep apnoea but with high pretest probability and a negative Autoset result polysomnography should be performed.
The Analysis of Eight Transcriptomes from All Poriferan Classes Reveals Surprising Genetic Complexity in Sponges
Authors: Ana Riesgo, Nathan Farrar, Pamela J. Windsor, Gonzalo Giribet, Sally P. Leys
Journal: Molecular Biology and Evolution (2014)

Sponges (Porifera) are among the earliest evolving metazoans. Their filter-feeding body plan based on choanocyte chambers organized into a complex aquiferous system is so unique among metazoans that it either reflects an early divergence from other animals prior to the evolution of features such as muscles and nerves, or that sponges lost these characters. Analyses of the Amphimedon and Oscarella genomes support this view of uniqueness—many key metazoan genes are absent in these sponges—but whether this is generally true of other sponges remains unknown. We studied the transcriptomes of eight sponge species in four classes (Hexactinellida, Demospongiae, Homoscleromorpha, and Calcarea) specifically seeking genes and pathways considered to be involved in animal complexity. For reference, we also sought these genes in transcriptomes and genomes of three unicellular opisthokonts, two sponges (A. queenslandica and O. carmela), and two bilaterian taxa. Our analyses showed that all sponge classes share an unexpectedly large complement of genes with other metazoans. Interestingly, hexactinellid, calcareous, and homoscleromorph sponges share more genes with bilaterians than with nonbilaterian metazoans. We were surprised to find representatives of most molecules involved in cell–cell communication, signaling, complex epithelia, immune recognition, and germ-lineage/sex, with only a few, but potentially key, absences. A noteworthy finding was that some important genes were absent from all demosponges (transcriptomes and the Amphimedon genome), which might reflect divergence from main-stem lineages including hexactinellids, calcareous sponges, and homoscleromorphs. Our results suggest that genetic complexity arose early in evolution as shown by the presence of these genes in most of the animal lineages, which suggests sponges either possess cryptic physiological and morphological complexity and/or have lost ancestral cell types or physiological processes.
Prognostic Value of the Molecular Detection of Circulating Tumor Cells Using a Multimarker Reverse Transcription-PCR Assay for Cytokeratin 19, Mammaglobin A, and HER2 in Early Breast Cancer
Authors: Michail Ignatiadis, Galatea Kallergi, Maria Ntoulia, Maria Perraki, Stella Apostolaki, Maria Kafousi, Grigorios Chlouverakis, Efstathios Stathopoulos, Evi Lianidou, Vassilis Georgoulias, Dimitris Mavroudis
Journal: Clinical Cancer Research (2008)

Abstract Purpose: To investigate the prognostic value of the molecular detection of circulating tumor cells (CTCs) using three markers [cytokeratin 19 (CK19), mammaglobin A (MGB1), and HER2] in early breast cancer. Experimental Design: CK19mRNA+, MGB1mRNA+, and HER2mRNA+ cells were detected using real-time (CK19) and nested (MGB1 and HER2) reverse transcription-PCR in the peripheral blood of 175 women with stage I to III breast cancer before the initiation of adjuvant chemotherapy. The detection of CTCs was correlated with clinical outcome. In 10 patients, immunofluorescence staining experiments were done to investigate the coexpression of cytokeratin, MGB1, and HER2 in CTCs. Results: CK19mRNA+, MGB1mRNA+, and HER2mRNA+ cells were detected in 41.1%, 8%, and 28.6% of the 175 patients, respectively. Patients had one of the following molecular profiles: CK19mRNA+/MGB1mRNA+/HER2mRNA+ (n = 8), CK19mRNA+/MGB1mRNA+/HER2mRNA− (n = 1), CK19mRNA+/MGB1mRNA−/HER2mRNA+ (n = 42), CK19mRNA+/MGB1mRNA−/HER2mRNA− (n = 21), CK19mRNA−/MGB1mRNA+/HER2mRNA− (n = 5), and CK19mRNA−/MGB1mRNA−/HER2mRNA− (n = 98). Double-immunofluorescence experiments confirmed the following CTC phenotypes: CK+/MGB1+, CK+/MGB1−, CK−/MGB1+, CK+/HER2+, CK+/HER2−, MGB1+/HER2−, and MGB1+/HER2+. In univariate analysis, the detection of CK19mRNA+, MGB1mRNA+, and HER2mRNA+ cells was associated with shorter disease-free survival (DFS; P &amp;lt; 0.001, P = 0.001, and P &amp;lt; 0.001, respectively), whereas the detection of CK19mRNA+ and MGB1mRNA+ cells was associated with worse overall survival (P = 0.044 and 0.034, respectively). In multivariate analysis, estrogen receptor–negative tumors and the detection of CK19mRNA+ and MGB1mRNA+ cells were independently associated with worse DFS. Conclusion: The detection of peripheral blood CK19mRNA+ and MGB1mRNA+ cells before adjuvant chemotherapy predicts poor DFS in women with early breast cancer.
Former head of NHS watchdog attacks MPs' inquiry into patient safety
Authors: A. O'Dowd
Journal: BMJ (2009)

The head of the former NHS watchdog, Ian Kennedy, has spoken out against MPs in the parliamentary health select committee about their recent inquiry into patient safety.

The committee published a special follow-up report on 4 November on this inquiry, which originally reported in July.

The latest report details responses from Professor Kennedy; Monitor, the independent regulator for NHS foundation trusts; and the current NHS watchdog, the Care Quality Commission.

Professor Kennedy said that he was “disappointed” at the views expressed in the original report about regulation in England and Wales by the Healthcare Commission, of which he was chairman before the Care Quality Commission …
Tuberculosis Pathogenesis and Immunity
Authors: Jennifer A. Philips, Joel D. Ernst
Journal: Annual Review of Pathology Mechanisms of Disease (2011)

Despite the development of potentially curative chemotherapy, tuberculosis (TB) continues to cause increasing worldwide morbidity and is a leading cause of human mortality in the developing world. Recent advances in bacterial molecular genetics, immunology, and human genetics have yielded insight into the molecular determinants of virulence, the immune responses that are essential for restricting progressive disease, and the determinants of immunopathology in TB. Despite these advances, a large knowledge gap still exists that limits the development and testing of new interventions, including novel drugs and efficacious vaccines. This review focuses on our current knowledge of TB pathogenesis and immunity that has been derived from in vitro and in vivo studies. In addition, it highlights topics that need to be better understood to provide improved means of controlling TB worldwide.
Multiplex Biomarker Approach for Determining Risk of Prostate-Specific Antigen-Defined Recurrence of Prostate Cancer
Authors: D. R. Rhodes, M. G. Sanda, A. P. Otte, A. M. Chinnaiyan, M. A. Rubin
Journal: JNCI Journal of the National Cancer Institute (2003)

Molecular signatures in cancer tissue may be useful for diagnosis and are associated with survival. We used results from high-density tissue microarrays (TMAs) to define combinations of candidate biomarkers associated with the rate of prostate cancer progression after radical prostatectomy that could identify patients at high risk for recurrence.Fourteen candidate biomarkers for prostate cancer for which antibodies are available included hepsin, pim-1 kinase, E-cadherin (ECAD; cell adhesion molecule), alpha-methylacyl-coenzyme A racemase, and EZH2 (enhancer of zeste homolog 2, a transcriptional repressor). TMAs containing more than 2000 tumor samples from 259 patients who underwent radical prostatectomy for localized prostate cancer were studied with these antibodies. Immunohistochemistry results were evaluated in conjunction with clinical parameters associated with prostate cancer progression, including tumor stage, Gleason score, and prostate-specific antigen (PSA) level. Recurrence was defined as a postsurgery PSA level of more than 0.2 ng/mL. All statistical tests were two-sided.Moderate or strong expression of EZH2 coupled with at most moderate expression of ECAD (i.e., a positive EZH2:ECAD status) was the biomarker combination that was most strongly associated with the recurrence of prostate cancer. EZH2:ECAD status was statistically significantly associated with prostate cancer recurrence in a training set of 103 patients (relative risk [RR] = 2.52, 95% confidence interval [CI] = 1.09 to 5.81; P =.021), in a validation set of 80 patients (RR = 3.72, 95% CI = 1.27 to 10.91; P =.009), and in the combined set of 183 patients (RR = 2.96, 95% CI = 1.56 to 5.61; P<.001). EZH2:ECAD status was statistically significantly associated with disease recurrence even after adjusting for clinical parameters, such as tumor stage, Gleason score, and PSA level (hazard ratio = 3.19, 95% CI = 1.50 to 6.77; P =.003).EZH2:ECAD status was statistically significantly associated with prostate cancer recurrence after radical prostatectomy and may be useful in defining a cohort of high-risk patients.
Theory of mind in nonhuman primates
Authors: C. M. Heyes
Journal: Behavioral and Brain Sciences (1998)

Since the BBS article in which Premack and Woodruff (1978) asked “Does the chimpanzee have a theory of mind?,” it has been repeatedly claimed that there is observational and experimental evidence that apes have mental state concepts, such as “want” and “know.” Unlike research on the development of theory of mind in childhood, however, no substantial progress has been made through this work with nonhuman primates. A survey of empirical studies of imitation, self-recognition, social relationships, deception, role-taking, and perspective-taking suggests that in every case where nonhuman primate behavior has been interpreted as a sign of theory of mind, it could instead have occurred by chance or as a product of nonmentalistic processes such as associative learning or inferences based on nonmental categories. Arguments to the effect that, in spite of this, the theory of mind hypothesis should be accepted because it is more parsimonious than alternatives or because it is supported by convergent evidence are not compelling. Such arguments are based on unsupportable assumptions about the role of parsimony in science and either ignore the requirement that convergent evidence proceed from independent assumptions, or fail to show that it supports the theory of mind hypothesis over nonmentalist alternatives. Progress in research on theory of mind requires experimental procedures that can distinguish the theory of mind hypothesis from nonmentalist alternatives. A procedure that may have this potential is proposed. It uses conditional discrimination training and transfer tests to determine whether chimpanzees have the concept “see.” Commentators are invited to identify flaws in the procedure and to suggest alternatives.
Colony-stimulating factors as an adjunct to chemotherapy in small cell lung cancer
Authors: T Urban, MP Schuller, B Lebeau
Journal: European Respiratory Journal (1996)

Myelosuppression is the major dose-limiting toxicity of chemotherapy in small cell lung cancer (SCLC). The capacity of colony stimulating factors (CSFs) to stimulate granular neutrophil recovery may be of great value to prevent or cure febrile neutropenia and to increase dose-intensity. The aim of this review was to assess the current use of CSFs in SCLC on the basis of experimental and clinical data. Primary CSF administration has been shown to reduce the incidence of febrile neutropenia, hospital admission rate, and antibiotic use subsequent to cyclophosphamidedoxorubicin-high dose etoposide (CDE) chemotherapy, without improvement of survival or disease control. Primary CSF administration may be recommended when the expected incidence of febrile neutropenia is at least 40%. This benefit has not been established with less myelosuppressive regimens, such as cisplatin-etoposide (PE), which remains an alternative combination of SCLC when standard doses are used. A trial comparing high-dose CDE + CSF with PE would be of considerable interest. There is currently little clinical basis for the use of CSFs to increase chemotherapy dose-intensity, outside clinical trials. Peripheral blood progenitor cells mobilized with CSFs offer interesting prospects. Further studies, with later initiation, shorter duration or lower doses of CSFs, are warranted to improve the cost-effectiveness of CSFs. CSF therapy in addition to antibiotics is normally not justified in febrile neutropenia, except perhaps in selected patients with sepsis syndromes, hypotension or pneumonia.