Continuous Dynamic Process Research Articles

Identifying strategies to maximise recruitment and retention of practices and patients in a multicentre randomised controlled trial of an intervention to optimise secondary prevention for coronary heart disease in primary care

BackgroundRecruitment and retention of patients and healthcare providers in randomised controlled trials (RCTs) is important in order to determine the effectiveness of interventions. However, failure to achieve recruitment targets is common and reasons why a particular recruitment strategy works for one study and not another remain unclear. We sought to describe a strategy used in a multicentre RCT in primary care, to report researchers' and participants' experiences of its implementation and to inform future strategies to maximise recruitment and retention.MethodsIn total 48 general practices and 903 patients were recruited from three different areas of Ireland to a RCT of an intervention designed to optimise secondary prevention of coronary heart disease. The recruitment process involved telephoning practices, posting information, visiting practices, identifying potential participants, posting invitations and obtaining consent. Retention involved patients attending reviews and responding to questionnaires and practices facilitating data collection.ResultsWe achieved high retention rates for practices (100%) and for patients (85%) over an 18-month intervention period. Pilot work, knowledge of the setting, awareness of change in staff and organisation amongst participant sites, rapid responses to queries and acknowledgement of practitioners' contributions were identified as being important. Minor variations in protocol and research support helped to meet varied, complex and changing individual needs of practitioners and patients and encouraged retention in the trial. A collaborative relationship between researcher and practice staff which required time to develop was perceived as vital for both recruitment and retention.ConclusionRecruiting and retaining the numbers of practices and patients estimated as required to provide findings with adequate power contributes to increased confidence in the validity and generalisability of RCT results. A continuous dynamic process of monitoring progress within trials and tailoring strategies to particular circumstances, whilst not compromising trial protocols, should allow maximal recruitment and retention.Trial registrationISRCTN24081411

What the Standard APTT Didn't Tell You - Dynamic Plasma Clotting Parameters Reveal Hypercoagulation.

Patients with a history of venous thrombosis have significantly shorter APTTs as compared with healthy references. The clinical feasibility of a short APTT is hindered because only a small number of patients have APTT values actually below the reference interval of healthy individuals. The APTT merely reflects the very early start of fibrin polymerization; however, clot formation is a continuous dynamic process. It may be speculated that additional prognostic information may be obtained from parameters describing the entire profile of the APTT clotting signal. Hence, we have developed algorithms to derive additional dynamic parameters from a continuous APTT plasma clotting signal, including the maximum velocity of fibrin formation (APTT-MaxVel). The aim of the present study was to characterize dynamic APTT profiles from patients with verified venous thrombosis. We hypothesized that the APTT-MaxVel was significantly accelerated in patients with a history of verified venous thrombosis as compared with healthy controls. A total of 46 patients, 19 males and 27 females, with a verified venous thrombosis were enrolled in the study. Fifty-two percentages of patients had a positive thrombophilia risk factor. Patients with antiphospholipid syndrome were not included. In total 89 healthy individuals, 43 males and 46 females, established a reference group. A standard APTT was recorded using platelet poor plasma, Platelin® as test reagent, and a BCT coagulation analyzer. The digital continuous clotting signal was exported and processed in a software program to derive dynamic coagulation parameters. Comparative statistics and un-paired t-tests were adopted to assess differences between groups and multiple linear regression was performed to predict the value of APTT-MaxVel from levels of FVIII:C and fibrinogen. P-values < 0.05 were considered statistical significant. Patients had a significantly more accelerated mean APTT-MaxVel (193.5 x/sec, SD=57, 95%CI: 176.6–210.4) as compared with healthy controls (137.3 x/sec, SD=21, 95%CI: 126.7–143.8). Patients also had a significantly shorter mean APTT (27.2 sec, SD=3.2, 95%CI: 26.3–28.2) than healthy controls (28.5 sec, SD=2.8, 95%CI: 27.9–29.1). Whereas only 1 of 46 (2.2%) patients had a standard APTT below the lower reference interval, 17 of the 46 (37%) patients had an APTT-MaxVel above the upper reference limit. Regression analysis revealed a linear correlation between FVIII:C, level of fibrinogen, and APTT-MaxVel (R2=0.89, p<0.05). Our data suggest that the APTT-MaxVel of fibrin formation represent a more sensitive marker for hypercoagulation in patients with verified venous thrombosis than standard APTT measures. The APTT-MaxVel may reflect the functional importance of both FVIII:C and level of fibrinogen. Additional studies are required to further assess the possible clinical and laboratory relevance of using dynamic parameters to predict risk of recurrent thrombosis.

Detection and continuation of a border collision bifurcation in a forest fire model

The behavior of the simplest forest fire model is studied in this paper through bifurcation analysis. The model is a second-order continuous-time impact model where vegetational growth is described as a continuous and slow dynamic process, while fires are modeled as instantaneous and disruptive events. The transition from Mediterranean forests (characterized by wild chaotic fire regimes) to savannas and boreal forests (where fires are almost periodic) is recognized to be a catastrophic transition known as border collision bifurcation in the context of discrete-tine systems. In the present case such a bifurcation can be easily detected numerically and then continued by solving a standard boundary-value problem. The result of the analysis complements previous simulation studies and are consistent with biological intuition.

Towards a Discrete Event Formalization of Sachem's Perception Based Monitoring

This paper aims at introducing the basis of the formalization of the Sachem perception based monitoring and diagnosis approach. Sachem is an extensive large-scale real time knowledge based system designed to monitor and diagnose blast furnaces. In this paper, Sachem is considered as a monitoring cognitive agent that analyzes a continuous dynamic process in order to generate discrete events (alarms) that inform about unsatisfactory process states occurences. The paper shows how the knowledge about the behavior of a continuous process can be formalized in terms of relation between discrete events so that a recursive recognition process of signatures can be used in order to design monitoring cognitive agents. The paper concludes on the main property of the discrete event representation of continuous process, the compactness.

Changes in eating habits following total and frontolateral laryngectomy

Swallowing is a continuous dynamic process, characterized by complex stages, that involves structures of the oral cavity, pharynx, larynx and esophagus. It can be divided into three phases: oral, pharyngeal and esophageal. Dysphagia is characterized by difficulty with, or the inability to swallow food of normal consistencies. To investigate the presence of swallowing difficulties and modifications made to the consistency of the food consumed in cases of total and partial laryngectomy, with or without subsequent radiotherapy, among patients who had not been diagnosed as having dysphagia. Descriptive study. Voice Clinic of São Paulo Hospital, Universidade Federal de São Paulo/Escola Paulista de Medicina, São Paulo, Brazil. 36 laryngectomy patients: 25 total and 11 frontolateral cases, were studied. A survey consisting of a 23-item questionnaire was applied by a single professional. Among those interviewed, 44% reported having modified the consistency of the food consumed (56% of the total and 20% of the partial frontolateral laryngectomy cases). It was not possible to investigate the influence of radiotherapy on the groups in this study, because the partial frontolateral laryngectomy cases were not exposed to radiotherapy. There was a higher incidence of complaints of swallowing difficulties in total laryngectomy cases (p < 0.027) than in partial frontolateral cases. However, there was no relationship between the surgery and weight loss. We also noted the patients' other problems regarding the eating process, as well as the compensation that they made for such problems. Research has shown an association between laryngectomy and swallowing difficulties, although there have been no reports of associated changes in eating habits among laryngectomized patients. This study showed that difficulty in swallowing is not rare in total and frontolateral laryngectomy cases. Such patients, even those who did not complain of dysphagia, also had minor difficulties while eating, and had to make some adaptations to their meals.

Serial Intraoperative Magnetic Resonance Imaging of Brain Shift

A major shortcoming of image-guided navigational systems is the use of preoperatively acquired image data, which does not account for intraoperative changes in brain morphology. The occurrence of these surgically induced volumetric deformations ("brain shift") has been well established. Maximal measurements for surface and midline shifts have been reported. There has been no detailed analysis, however, of the changes that occur during surgery. The use of intraoperative magnetic resonance imaging provides a unique opportunity to obtain serial image data and characterize the time course of brain deformations during surgery. The vertically open intraoperative magnetic resonance imaging system (SignaSP, 0.5 T; GE Medical Systems, Milwaukee, WI) permits access to the surgical field and allows multiple intraoperative image updates without the need to move the patient. We developed volumetric display software (the 3D Slicer) that allows quantitative analysis of the degree and direction of brain shift. For 25 patients, four or more intraoperative volumetric image acquisitions were extensively evaluated. Serial acquisitions allow comprehensive sequential descriptions of the direction and magnitude of intraoperative deformations. Brain shift occurs at various surgical stages and in different regions. Surface shift occurs throughout surgery and is mainly attributable to gravity. Subsurface shift occurs during resection and involves collapse of the resection cavity and intraparenchymal changes that are difficult to model. Brain shift is a continuous dynamic process that evolves differently in distinct brain regions. Therefore, only serial imaging or continuous data acquisition can provide consistently accurate image guidance. Furthermore, only serial intraoperative magnetic resonance imaging provides an accurate basis for the computational analysis of brain deformations, which might lead to an understanding and eventual simulation of brain shift for intraoperative guidance.

Adaptive switched control of plants with unknown relative degree

Abstract A logic-based switched control system is a concrete example of hybrid systems, consisting of the mode switcher and the continuous dynamic process to be controlled. The control laws involved in such systems are typically of the form: u = fi(•) (i = 1,2, …, n), namely, if ith event occurs, then switch to control law fi. This can be equivalently written as u = θT F(•), where θ and F are appropriate parameter vector and function vector respectively. To implement the control law, we have to identify the n events in the control process, otherwise it would not be implementable. Alternatively, we may regard θ as a design parameter that can not be decided a priori due to insufficient information of the controlled plant. In this paper, we shall employ adaptive techniques to determine θ, in the context of adaptive control for the plants with unknown relative degree. Instead of identifying events, we introduce an adaptive mechanism which can adaptively determine θ using input and output information of the controlled process. We believe that the proposed idea can be generalized to a broad class of switched control systems.

Low density lipoprotein binding induces asymmetric redistribution of the low density lipoprotein receptors in endothelial cells

The uptake and transport of cholesterol-carrying low density lipoprotein (LDL) by the arterial wall is a continuous dynamic process, contributing to the cholesterol homeostasis in the plasma and in the cellular components of the vessel wall. Upon exposure to endothelial cells (EC), LDL interacts in part, with specific surface receptors (LDL-R). In this study we questioned: (i) the distribution of LDL receptors on the apical and basal cell membranes in endothelial cells; (ii) the role of LDL receptors in the control of cholesterol homeostasis and (iii) the translocation of LDL receptor across the EC. To this purpose bovine aortic EC were cultured on filters in a double-chamber system, in Dulbecco's medium supplemented either with 10% fetal calf serum (FCS) or with 10% lipoprotein-deficient serum (LPDS). The cells were exposed for 3h to 13H]acetate (40 microCi) added to both compartments of the cell culture inserts. The newly synthesized [3H]cholesterol was detected by thin layer chromatography and quantified by liquid scintillation counting. The LDL-R were detected in EC protein homogenates by immunoblotting using a monoclonal antibody against LDL-R (IgG-C7); the intracellular pathway of LDL-R was examined by electron microscopy using a complex made of protein A 5 nm or 20 nm colloidal gold particles and an anti-LDL receptor antibody (Au-PA-C7). To evaluate the distribution and the transport of LDL-R from one cell surface to the other, EC grown in LPDS were radioiodinated either on the apical or on the basolateral surface, incubated on the same surface with LDL, and subsequently biotinylated on the opposite non-radiolabeled surface. The EC were further solubilized and the protein extract immunoprecipitated with anti-LDL-R antibody or with mouse IgG (as control). The eluted antigen-antibody complexes were precipitated with streptavidin-agarose beads, solubilized, and subjected to SDS-PAGE. The results showed that: (a) the LDL-R were present on both endothelial cell fronts; (b) using the complex Au-PA-C7, the LDL-R were localized in endothelial plasmalemmal vesicles as well as coated pits and coated vesicles in multivesicular bodies and lysosomes, irrespective of the cell surface exposed to the complex; (c) biochemical assays indicated that upon ligand binding, the LDL-R were translocated preferentially from the apical to the basal plasma membrane.

Tax reform from the gradient projection viewpoint

This paper examines the problems of gradual tax reform. Desirable small moves of the tax system are determined using the principles of the well-known gradient projection algorithm. Three classical models of public finance are considered. For each of them a continuous time dynamic process is exhibited along which the social welfare function increases until convergence to local second best extrema. Although the selection of trajectories according to the gradient projection method has some arbitrariness, it leads to intuitively and economically appealing rules such as a tax reform analog of the classical optimal taxation result on production efficiency.

Workshop IV—Fiber, lipids, and cardiovascular disease Summary and recommendations

Evidence related to the influence of dietary fiber on cardiovascular disease in man is epidemiological in nature. Indeed, in the absence of an ante mortem test for the impending event, all dietary and environmental factors correlated with the incidence of heart disease are regarded as risk factors and represent statistical rather than medical diagnoses, albeit some correlations are highly significant. Experimental atherosclerosis provides a more direct test of hypotheses, but the disease does not always resemble human disease. The field of experimental atherosclerosis has not defined the ideal animal model. Work is now being carried out in primates, swine, rabbits, and birds, with each model having advantages and drawbacks. Animal studies with fiber must be examined in the light of suitability of a particular species for atherosclerosis research. Data derived from human or animal studies represent work done with a mixed diet whose total fiber content can be determined or with specific materials such as bran, alfalfa, cellulose, and pectin. We could regard the components of a mixed diet as the natural form of ingested fiber, whereas specific purifled materials (such as pectin) or materials that may vary from sample to sample (such as alfalfa or bran) could be thought of as therapeutic dietary additives. The principal problem involves identification ofthe specific component of fiber responsible for the observed results. We will also need to learn if fiber extracted from a foodstuff functions as it does in the natural state, in situ as it were. We need better data on the composition of fiber present in the general diet; this calls for a standardized analytic methodology. We will then be in a position to assess the mode(s) of action of cellulose, hemicellulose, pectin, hgnm, and gums and to determine the synergistic or antagonistic relationships among them. The effects of dietary fiber are part of the digestive process and, as such, represent a continuous dynamic process. Current work involves application of parameters of equihibrium systems to this process. Perhaps our perceptions of how fiber works should be altered. It may be that a biological as well as a chemical definition of fiber may be required.

Differential Analysis of Opacification in Angiocardiography

Each individual exposure in an angiocardiogram gives a picture of the arrested motion of the heart in successive stages of opacification. By combining these isolated views in a graph, a continuous dynamic process can be visualized. The chambers of the heart can be analyzed separately, and by correlating the opacification in the various chambers, the function of the heart as a whole can be studied.