Reporting problems with medical foods.
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Food, Formulated↗
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[Systematic principles for quantitative pathomorphological studies].
The single steps are depicted of an analysis of biological systems by quantitative pathomorphological investigations. After mathematical description and modelling, principles and biological laws can be formulated. The complex view of the problems should provide a theoretical base for the prospective development of quantitative pathomorphology.
Animals↗
[Pyloric occlusion caused by calculi in patients with cholecysto-gastric fistula].
Personal experience with a case of pyloric occlusion due to calculi in a woman with spontaneous cholecysto-gastric fistula is reported. A general picture of this rare condition is described and the clinical case and the therapy adopted are illustrated. The problems that may be encountered in formulating a precise preoperative diagnosis when the age of the patient and serious general condition do not permit routine investigations are presented.
Aged↗
Delisting of drugs in Ontario. How attitudes and prescribing strategies of family physicians in the Kingston area changed.
OBJECTIVE: To assess how attitudes and prescribing strategies of family physicians changed when drugs were delisted from the Ontario Drug Benefit formulary. DESIGN: Mailed, self-administered survey. SETTING: Family physicians' offices in Ontario. PARTICIPANTS: All family physicians practising in the Kingston, Frontenac, Lennox, and Addington Health District. MAIN OUTCOME MEASURES: Physicians were presented with six vignettes involving patients receiving a delisted drug. The choices were to recommend the patient pay for the medication, to substitute a drug still listed on the formulary, to make a special request that the medication be covered for this patient, or to offer another option. As well, the physicians were asked to indicate, on a 5-point Likert scale, their opinions regarding the effect of delisting on themselves and their patients. RESULTS: Physicians were most likely to change to a medication that was still on the formulary. Patient sex and ability to pay were factors in physicians' decisions. Physicians believe that the delistings are not likely to have adversely affected patients' health, that noncompliance is a problem because many once-daily formulations have been removed, that suitable alternatives are not always available, and that physicians should have been consulted more before the changes were made. CONCLUSIONS: Physicians usually substitute listed medications for medications that have been delisted. This is especially true for female patients and patients who are unable to pay.
Adult↗
[Radiation and immunity. Contemporary view of old problems].
Some key problems of radiation immunology which were formulated during last decades have been considered. The possibility or their decision appeared at recent time proceeding from the new view on the ionizing irradiation as a source of biologically significant signals. From that point of view some experimental data concerning radiation effects on the maturation and selection of lymphocytes, contact interaction of immune system cells and cytokine network were reviewed. It was concluded that the disturbances of the spatial and temporary organization and integrative functions of immune system were the results of the non-adequate radiation-induced signalling.
Animals↗
[Community nursing from the viewpoint of public health].
Findings of health science as to the incidence and dynamics of health problems and the knowledge to optimize health promotion, prevention and patient treatment as well as international comparisons indicate that the potentials of nursing--understood as a system of nurses, nursing institutions and nursing science differentiated in itself--are not exhausted to their full extent within the German system of social health assurance. Following the introductory reflections on the relation between public health and nursing, being relatively young multi-disciplines of health science in Germany, this paper tries to identify and to describe the related deficiencies and approaches for their rectification by means of the four phases of the Public Health Action Cycle--assessment: of problems and fixing of priorities; policy formulation: selection, negotiation and fixing of strategies; assurance: organisation, implementation and control as well as evaluation: evaluation of the strategy and its results. This paper is the revised version of the basic lecture that the author gave on the occasion of the Fourth International Symposium of Nursing Science in Osnabrück in November 1996.
Community Health Nursing↗
Design of H(infinity) robust fault detection filter for linear uncertain time-delay systems.
In this paper, the robust fault detection filter design problem for linear time-delay systems with both unknown inputs and parameter uncertainties is studied. Using a multiobjective optimization technique, a new performance index is introduced, which takes into account the robustness of the fault detection filter against disturbances and sensitivity to faults simultaneously. The reference residual model is then designed based on this performance index to formulate the robust fault detection filter design problem as an H(infinity) model-matching problem. By applying robust H(infinity) optimization control technique, the existence condition of the robust fault detection filter for linear time-delay systems with both unknown inputs and parameter uncertainties is presented in terms of linear matrix inequality formulation, independently of time delay. In order to detect the fault, an adaptive threshold which depends on the inputs is finally determined. An illustrative design example is used to demonstrate the validity of the proposed approach.
Journal Article↗
Quality-of-life assessment in health care research and practice.
This article reviews the different ways in which quality-of-life assessment has been applied to and has affected health care research and practice. A schema that describes the steps involved in the ongoing challenge of improving health outcomes is used to structure the review. The role of quality-of-life assessment is addressed with regard to: the identification of health problems, the evaluation of new treatments, the formulation of treatment guidelines and health policies, the delivery of optimal care in practice, and the assessment of outcomes in the wider community. The benefit of quality-of-life assessment has been demonstrated in a number of these areas (e.g., in identifying problems and evaluating treatments). Its role in other applications (e.g., in clinical practice to assess patients' needs) shows great promise and requires additional evaluation.
Delivery of Health Care↗
Pharmacokinetics and pharmacodynamics of qinghaosu derivatives: how do they impact on the choice of drug and the dosage regimens?
The critical decisions of which artemisinin derivative(s) to use and by which route(s) of administration for falciparum malaria are complex scientifically and politically. Despite the need for additional pharmacokinetic, pharmacodynamic and toxicokinetic data, these drugs are too important to delay concise, rational recommendations any longer. These types of decisions must be made now, implemented on a multinational level with WHO leadership, and revised as new findings emerge. For acute, uncomplicated disease, per os dosing of artesunate or artemether for three days is recommended, but only in combination with other antimalarial drugs like mefloquine. For severe falciparum malaria, intravenous administration is the preferred route, yet current formulations for intravenous dosing are not optimal and should be an area for future development emphasis. Clearly intramuscular administration of artemether has proven effective for severe disease, yet dosing regimens shouldn't be designed with ultimate parasitological cure as the aim and the problem of bioavailability of the sesame oil formulations must be examined further. Once the life-saving reduction in parasitemia and pathophysiological sequelae have been achieved, the patient can be given oral medication to affect radical cure. Much more data will be required to define the role of per rectum dosing for the treatment of severe malaria, yet this approach holds great promise as a life-saving intervention in rural areas where this disease has it most dramatic impact.
Administration, Oral↗
PH-dependent drug release from certain commercial tablets.
A dissolution-dialysis profile for each of several brands of nitrofurantoin, hydrochlorothiazide and sulfisoxazole tablets was developed at three pH levels. The study used a two-compartment diffusion cell with a semipermeable cellophane membrane. Nitrofuratoin tablets were tested at pH values of 7.2, 4.7 and 1.2; sulfisoxazole tablets at 7.2, 5.5 and less than 1. Studies with hydrochlorothiazide tablets were terminated because the pH of the dissolution medium had no effect of practical significance on dissolution or dialysis rates. The dissolution rates of the nitrofurantoin and sulfisoxazole tablets were highly brand-individualized and complex. The effects of pH upon a particular formulation were unpredictable. The results suggest that dissolution testing at one fixed pH, as commonly practiced, may be insufficient for some products. This pH-dependent release characteristic may not correspond to a change in bioavailability in all cases, but it represents a potential problem which should be considered by the formulator.
Biological Availability↗
Use of genetic algorithms to solve biomedical problems.
Many problems in the biomedical sciences can be formulated as searches in some appropriate space. The genetic algorithm offers a domain-independent approach to searching that is often able to provide good answers to questions with difficult search spaces. This paper discusses when to use this genetically inspired approach, how to model problems as searches, how to define appropriate spaces, representations, and fitness functions, and how to implement a program using a genetic algorithm.
Algorithms↗
A comparison of finite element codes for the solution of biphasic poroelastic problems.
The extent to which three finite element codes can solve problems in biphasic poroelasticity is examined. Both linear and non-linear (that is where the permeability of the material is a function of deformation) formulations are studied using the standard confined compression problem as an example. The results are compared, where possible, to the results of Spilker, Suh and Mow who first presented a solution to this problem for cartilage. The agreement is excellent for the linear case. For the non-linear case, the solutions do differ slightly; however, the difference would not appear to be significant.
Biomechanical Phenomena↗
Calculation of photon dose distributions in an inhomogeneous medium using convolutions.
A formulation of the single energy photon transport problem is cast in the form of a series of convolutions over the primary fluence distribution with invariant kernels. A method is developed for compensating for the variant intervoxel attenuation in the scattered dose distribution by means of an invariant correction kernel. Results of applying the formulation to 60Co distributions in the presence of slab and block inhomogeneities are presented.
Cobalt Radioisotopes↗
A stochastic deconvolution method to reconstruct insulin secretion rate after a glucose stimulus.
Insulin secretion rate (ISR) is not directly measurable in man but it can be reconstructed from C-peptide (CP) concentration measurements by solving an input estimation problem by deconvolution. The major difficulties posed by the estimation of ISR after a glucose stimulus, e.g., during an intravenous glucose tolerance test (IVGTT), are the ill-conditioning of the problem, the nonstationary pattern of the secretion rate, and the nonuniform/infrequent sampling schedule. In this work, a nonparametric method based on the classic Phillips-Tikhonov regularization approach is presented. The problem of nonuniform/infrequent sampling is addressed by a novel formulation of the regularization method which allows the estimation of quasi time-continuous input profiles. The input estimation problem is stated into a Bayesian context, where the a priori known nonstationary characteristics of ISR after the glucose stimulus are described by a stochastic model. Deconvolution is tackled by linear minimum variance estimation, thus allowing the derivation of new statistically based regularization criteria. Finally, a Monte-Carlo strategy is implemented to assess the uncertainty of the estimated ISR arising from CP measurement error and impulse response parameters uncertainty.
C-Peptide↗
Algorithms for computing and integrating physical maps using unique probes.
Current physical mapping projects based on STS-probes involve additional clues such as the fact that some probes are anchored to a known map and that others come from the ends of clones. Because of the disparate combinatorial contributions of these varied data items, it is difficult to design a "tailored" algorithm that incorporates them all. Moreover, it is inevitable that new experiments will provide new kinds of data, making obsolete any such algorithm. We show how to convert the physical mapping problem into a 0/1 linear programming (LP) problem. We further show how one can incorporate additional clues as additional constraints in the LP formulation. We give a simple relaxation of the 0/1 LP problem, which solves problems of the same scale as previously reported tailored algorithms, to equal or greater optimization levels. We also present a theorem proving that when the data is 100% accurate, then the relaxed and integer solutions coincide. The LP algorithm suffices to solve problems on the order of 80-100 probes--the typical size of the 2- or 3-connected contigs of Arratia et al. (1991). We give a heuristic algorithm which attempts to order and link the set of LP-solved contigs. Unlike previous work, this algorithm only links and orders contigs when the join is 90% or more likely to be correct. It is our view that there is no value in computing an optimal solution with respect to some criteria over very noisy data as this optimal solution rarely corresponds to the true solution. The paper involves extensive empirical trials over real and simulated data.
Algorithms↗
On peptide de novo sequencing: a new approach.
A procedure is presented for the automatic determination of the amino acid sequence of peptides by processing data obtained from mass spectrometry analysis. This is a basic and relevant problem in the field of proteomics. Furthermore, it has an even higher conceptual and applicative interest in peptide research, as well as in other connected fields. The analysis does not rely on known protein databases, but on the computation of all amino acid sequences compatible with the given spectral data. By formulating a mathematical model for such combinatorial problems, the structural limitations of known methods are overcome, and efficient solution algorithms can be developed. The results are very encouraging both from the accuracy and computational points of view.
Algorithms↗
Boundary element method analysis for the bioheat transfer equation.
In this paper, the boundary element method (BEM) approach is applied to solve the Pennes (1948) bioheat equation. The objective is to develop the BEM formulation and demonstrate its feasibility. The basic BEM formulations for the transient and steady-state cases are first presented. To demonstrate the usefulness of the BEM approach, numerical solutions for 2-D steady-state problems are obtained and compared to analytical solutions. Further, the BEM formulation is applied to model a conjugate problem for an artery imbedded in a perfused heated tissue. Analytical solution is possible when the conduction in the x-direction is negligible. The BEM and analytical results have very good agreement.
Algorithms↗
ABI 007.
ABI 007 is an albumin-stabilised nanoparticle formulation of paclitaxel designed to overcome insolubility problems encountered with paclitaxel. This then eliminates the need for toxic solvents like cremophor, which limits the dose of paclitaxel that can be administered and hence effect overall drug efficacy. ABI 007 is being developed for the treatment of a variety of tumour types by American Pharmaceutical Partners. In addition to the standard infusion formulation of ABI 007, oral and pulmonary delivery formulations are also being investigated. American Pharmaceutical Partners, a subsidiary of American BioScience, secured exclusive North American marketing and manufacturing rights to ABI 007 from American BioScience in November 2001. American BioScience completed a phase III study in the US in metastatic breast cancer patients in early 2003. An indication for which ABI 007 was granted fast track status in January 2003. The phase III study directly compared the efficacy of ABI 007 260 mg/m(2) with paclitaxel 175 mg/m(2). Both agents were administered every 3 weeks. ABI 007 was administered as a 30-minute infusion without steroid pretreatment. Paclitaxel-treated patients received steroid pretreatment and the drug was administered over 3 hours. In October 2002, a Data Monitoring Committee concluded that a sample size adjustment of the phase III trial would not be required and that the study can be continued to completion. Enrolment was completed in December 2002 with 460 first- and second-line metastatic breast cancer patients enrolled. The results were expected to be unblinded in mid-2003. A phase II trial of ABI 007 is also underway in metastatic breast cancer patients who have failed taxane therapy. The trial is evaluating a weekly rather than 3-weekly regimen of ABI 007. Earlier, in May 2003, American Pharmaceutical Partners reported that ABI 007 is also being evaluated for the treatment of non-small cell lung cancer, ovarian cancer, melanoma and cervical cancers. However, the phase of development for these indications remains unclear.
Albumin-Bound Paclitaxel↗