Background Quality improvement in general practice has increasingly focused on the analysis of its clinical databases to guide its improvement strategies. However, general practitioners (GPs) need to ...be motivated to extract and review their clinical data, and they need skills to do so. This study examines the initial experience of 15 practices in undertaking clinical data extraction and management and the support they were given by their local division of general practice. Objectives To explore the uptake of data extraction tools in general practice and understand how divisions of general practice can assist with their uptake. Method This study was conducted within a single division of general practice within the south-eastern suburbs of metropolitan Melbourne, Australia. Self-selected practiceswere offered a data extraction program ('tool') free of charge, with ongoing division support. Practice representatives, either GPs, practice nurses or other practice staff members, were given instructions on how to extract data using the data extraction tool. This was followed by discussion with division staff regarding which clinical areas might be focused on. Division staff systematically recorded information about the experience of the practices and collated their clinical data. Results Fifteen practices, representing 69 GPs, participated. The practices chose from the following areas to work on as quality improvement activities: improving data entry; inactivating patient files for those who no longer attended the practice; correcting demographic information; diabetes and coronary heart disease management. The recording of data, according to the extraction tool, was found to be incomplete. For example, one-third of the patients who had HbA1cs recorded were on target, i.e. <7%, but nearly half the patients with diabetes did not have HbA1cs recorded at all. About half the patients with coronary heart disease were not reported as taking aspirin and one-third were not on a statin. Nearly half the patients who had attended their practice in the previous 30 months did not have smoking status recorded. Conclusion While data extraction programs provide GPs with useful tools for examining their clinical databases and identifying clinical practice issues which could be improved, external support, such as that provided by divisions, is helpful. Technical barriers, such as the failure of extraction tools to recognise some data and the failure to comprehensively enter data, are impediments, but in spite of these considerable interest exists in the use of clinical data to improve practice.
In Australia, no therapeutic agents were subsidised for the treatment of idiopathic pulmonary artery hypertension (iPAH), a rare progressive and severe disease with short life expectancy, until 1 ...March 2004, when bosentan (a dual endothelin receptor antagonist of high cost) was listed on the Pharmaceutical Benefits Scheme (PBS). Bosentan, in addition to conventional therapy, has been shown to slow iPAH progression and improve clinical and haemodynamic status and symptomatology, compared with placebo and conventional therapy. The objective of this paper is to describe the process of the Australian Pharmaceutical Benefits Scheme listing for bosentan (Tracleer), which included a health economic model assessing the cost effectiveness of bosentan from a healthcare payer perspective, and a risk-sharing arrangement based on the establishment of a patient registry.
The health economic model predicted the cost, hospitalisation and mortality rates of a population of iPAH patients treated with either the conventional therapy regimen used in Australia or bosentan plus the conventional therapy regimen. The model was implemented as a first-order Monte Carlo simulation with mortality modelled directly as the main clinical outcome. The impacts of proposed continuation criteria, restricting the ongoing use of the drug, were evaluated. Costs and outcomes were discounted at 5% and a sensitivity analysis examined the robustness of the key assumptions.
The model predicted that after 5, 10 and 15 years, the difference in average cumulative costs between bosentan plus conventional therapy and conventional therapy alone would be 116,929 Australian dollars (A dollars), A181,808 dollars and A216,331 dollars for each patient, respectively. There would be an associated increase in average life expectancy of 1.39, 2.93 and 3.87 years at 5, 10 and 15 years, respectively, with an incremental cost-effectiveness ratio at 15 years of A55,927 dollars for each life-year gained. Removing the continuation criteria from the model increased the incremental cost-effectiveness ratio to A62,267 dollars (1996-2002 values).
Economic modelling based on improved survival suggests bosentan to be a potentially cost-effective treatment for iPAH. However, the structure of the model and its inputs should be reviewed and updated as more data become available.
The maintenance of blood glucose homeostasis is complex and involves several key tissues. Most of these tissues are not easily accessible, making direct measurement of the physiological parameters ...involved in glucose metabolism difficult. The use of isotope tracer methodology and mathematical modeling allows indirect estimates of in vivo glucose metabolism through relatively noninvasive means. The purpose of this paper was to provide a mathematical synthesis of the models developed for describing glucose kinetics. As many of the models were developed using dogs, example data from the canine literature are presented. However, examples from the human and feline literature are also given in the absence of dog data. The glucose system is considered in both the steady and nonsteady states, and the models are examined by grouping them into schemes consisting of one, two, and three glucose compartments. Noncompartmental schemes are also considered briefly.
Effects of aging on inflammation and blood flow in the brain are unclear. Young (three to six months) and aged (19-22 months) male Brown Norway Fisher rats were used to compare (i) leukocyte function ...in nonischemic conditions and (ii) leukocyte function and hemodynamic changes after ischemia-reperfusion (I-R). In nonischemic studies, polymorphonuclear (PMN) CD11b expression and reactive oxygen species (ROS) production were measured with flow cytometry and PMN chemotaxis was measured with a Boyden chamber (+/-fMLP). In I-R studies, ischemia was induced by bilateral carotid artery occlusion and hypotension (20 minutes). During early reperfusion (30 minutes), leukocyte adhesion and rolling and blood-shear rates were measured using fluorescence microscopy. During late reperfusion (48 hours), mortality, neurological function, and leukocyte infiltration were measured. Stimulated PMN chemotaxis was increased in nonischemic aged rats (p < 0.05). In early reperfusion, there was a significant increase in leukocyte rolling and adhesion in the cerebral microcirculation and a significant decrease in shear rate in aged rats, compared to the young (p < 0.05). During late reperfusion, neurologic function was worse in aged vs. young rats (p < 0.05). These findings suggest that increased intravascular PMN adhesion and vascular dysfunction may contribute to poor neurologic outcome after cerebral I-R in the aged brain.
Since the mid-1980s, attempts to think history and literature together have produced much exciting work in the humanities. Indeed, some form of historicism can be said to inform most of the current ...scholarship in literary studies, including work in poetics, yet much of this scholarship remains undertheorized. Envisioning a revitalized and more expansive historicism, this volume builds on the tradition of Historical Poetics, pioneered by Alexander Veselovsky (1838-1906) and developed in various fruitful directions by the Russian Formalists, Mikhail Bakhtin, and Olga Freidenberg. The volume includes previously untranslated texts of some of the major scholars in this critical tradition, as well as original contributions which place that tradition in dialogue with other thinkers who have approached literature in a globally comparatist and evolutionary-historical spirit. The contributors seek to challenge and complement a historicism that stresses proximate sociopolitical contexts through an engagement with the longue duree of literary forms and institutions. In particular, Historical Poetics aims to uncover deep-historical stratifications and asynchronicities, in which formal solutions may display elective affinities with other, chronologically distant solutions to analogous social and political problems. By recovering the traditional nexus of philology and history, Persistent Forms seeks to reinvigorate poetics as a theoretical discipline that would respond to such critical and intellectual developments as Marxism, New Historicism, the study of world literature, practices of distant reading, and a renewed attention to ritual, oral poetics, and genre.
Diabetes and obesity lead to a significantly reduced quality of life, with an increased risk of serious complications including cardiovascular disease, hypertension, stroke, kidney failure and nerve ...damage. Human pancreatic alpha‐amylase (HPA) provides a unique opportunity for the development of potential therapeutic agents for the treatment of these conditions. This enzyme plays a vital role in the breakdown of starch in the diet, and its activity has been correlated to postprandial blood glucose levels, the control of which is essential for maintaining quality of life for diabetic patients. Nonetheless, the discovery of specific high affinity inhibitors for HPA has proven elusive and the currently available therapies that target this enzyme cause many deleterious side effects due to their activity on a wide range of glycosidases. In an attempt to identify new inhibitors of HPA, we have screened over 80,000 pure chemicals and crude biological extracts. This has resulted in the exciting discovery of montbretin A, a glycosylated acyl flavonol that acts as a competitive HPA inhibitor with a Ki of 8.1 nM. Structural characterization of the binding mode of fragments of the montbretin A molecule have been undertaken and a model of montbretin A binding proposed. This work is supported by the Canadian Institutes of Health Research.
Drugs that inhibit the cardiac rapid delayed rectifier potassium ion current (
I
Kr) channel can be proarrhythmic and their clinical use has been associated with sudden unexpected death (SUD). Since ...SUD is about 20 times more common among people with epilepsy than in the general population, and some data indicate that drug treatment may contribute, we tested the hypothesis that the classic antiepileptic drugs phenytoin (PHT), carbamazepine (CBZ), and phenobarbital (PB) have a potential to block
I
Kr. The whole cell patch-clamp recording technique was used to study the effects on
I
Kr channels expressed by the human ether-a-go-go related gene (HERG) stably expressed in Human Embryo Kidney (HEK) 293 cells. Tail currents, which are purely related to HERG, were blocked with an IC
50 (the concentration when 50% inhibition was obtained compared to control values) of 240
μM for PHT and 3
mM for PB. A 20% inhibition of tail currents was obtained at CBZ concentrations of 250 and 500
μM. Collective data show that drugs with the same margins (ratio HERG IC
50/unbound therapeutic concentration), as PHT and PB, may have arrhythmogenic potential, especially when used in predisposed patients and in the case of drug–drug interactions. SUD in epilepsy is generally a seizure-related phenomenon. However, our data suggest that PHT and PB may play a contributing role, perhaps by making some patients more vulnerable to the cardiovascular depression induced by seizures.
Land and labor, 1866-1867 Hayden, Rene; Kaye, Anthony E; Masur, Kate ...
08/2013, Letnik:
series 3
eBook
Land and Labor, 1866-1867 examines the remaking of the South's labor system in the tumultuous aftermath of emancipation. Using documents selected from the National Archives, this volume of Freedom: A ...Documentary History of Emancipation depicts the struggle of unenfranchised and impoverished ex-slaves to control their own labor, establish their families as viable economic units, and secure independent possession of land. Among the topics addressed are the dispossession of settlers in the Sherman reserve, the reordering of labor on plantation and farm, nonagricultural labor, new relations of credit and debt, long-distance labor migration, and the efforts of former slaves to rent, purchase, and homestead land. The documents--many of them in the freed people's own words--speak eloquently for themselves, while the editors' interpretive essays provide context and illuminate major themes.
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