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Biomedical subjects

A Alban

Publications and source records attributed to A Alban.

At least 19 recordsLinked to original sources
PubMed2001

[Utilization of health care system by patients with chronic pain who apply for disability pensions. A registry study].

INTRODUCTION: Patients with chronic pain may be awarded a disability pension if their working capacity is reduced as a result of an illness. Patients with chronic pain very often consult several specialists in order to obtain proof of their illness. The aim of this study was to investigate how an application for disability pension affected the utilization of health care services by patients with chronic pain. METHOD: Patients with chronic pain who applied for a disability pension in 1989 and 1990 were entered. The study period was divided into three: the year preceding the submission of the application for a disability pension, the time from submission of the application to the making of the decision, and the year following the decision of the health authorities. The patients were divided into four subgroups according to whether the disability pension was awarded or rejected, and whether the patients accepted or appealed the decision. The total costs of care in the primary sector were calculated on the number of and charges for visits to GPs and the total costs of hospital care were calculated on the number of bed days, visits to outpatients clinics, operations, and investigations. RESULTS: Patients with chronic pain had a significantly lower health care utilisation after the case has been closed. Those who did not get a disability pension and those who were not satisfied with the level of the disability pension, continued their utilisation of health care after the decision. The mean health care used by patients who appealed the level of the disability pension was three times higher than that used by patients who accepted the level of the disability pension. CONCLUSION: The study indicates that lack of or insufficient economic compensation from the social system in patients with chronic pain may contribute to inexpedient behaviour leading to increased costs to the health care sector.

Chronic Disease↗
PubMed2001

Purification of poly-ubiquitinated proteins by S5a-affinity chromatography.

Poly-ubiquitination, the post-translational covalent conjugation of isopeptide-linked chains of ubiquitin to other target proteins, is the central signal for proteolytic degradation by the 26S proteasome complex. The S5a subunit of the 26S proteasome binds poly-ubiquitin chains containing four or more ubiquitins. We have used an immobilised glutathione-S-transferase (GST)-S5a fusion protein to purify poly-ubiquitinated proteins from mammalian tissues, with the intention of expanding the repertoire of known substrates of the ubiquitin pathway. A complex mixture of poly-ubiquitinated proteins was successfully purified from normal pig brain extract following induction of in vitro ubiquitination. Western blots of two-dimensional gels of this mixture showed at least two diagonal series of ubiquitin-positive spots. Individual spots in each series were separated by approximately 9 kDa suggesting that they represent poly-ubiquitinated proteins with increasing numbers of ubiquitins in the chains. S5a-binding proteins purified from ubiquitination-induced human placental extracts, resolved by sodium dodecyl sulfate polyacrylamide gel electrophoresis and visualised by Coomassie staining, contained a single major species with an apparent denatured molecular mass of approximately 60 kDa. Edman degradation identified this protein as hHR23B, a human homologue of the Saccharomyces cerevisiae DNA repair protein Rad23p. In this case hHR23B is not ubiquitinated but instead contains an intrinsic ubiquitin-like domain at its N-terminus, through which it interacts with S5a (Hiyama, H., et al., J Biol. Chem. 1999, 274, 28,019-28,025).

Animals↗
PubMed2001

The ubiquitin protein catabolic disorders.

The ubiquitin-proteasome system of intracellular proteolysis is essential for cell viability. We propose the concept that neurodegenerative diseases such as Alzheimer's and Parkinson's, as well as other conditions including some types of cancer, collectively represent a raft of 'ubiquitin protein catabolic disorders' in which altered function of the ubiquitin-proteasome system can cause or directly contribute to disease pathogenesis. Genetic abnormalities within the ubiquitin pathway, either in ubiquitin-ligase (E3) enzymes or in deubiquitinating enzymes, cause disease because of problems associated with substrate recognition or supply of free ubiquitin, respectively. In some cases, mutations in protein substrates of the ubiquitin-proteasome system may directly contribute to disease progression because of inefficient substrate recognition. Mutations in transcripts for the ubiquitin protein itself (as a result of 'molecular misreading') also affect ubiquitin-dependent proteolysis with catastrophic consequences. This has been shown in Alzheimer's disease and could apply to other age-associated neurodegenerative conditions. Within the nervous system, accumulation of unwanted proteins as a result of defective ubiquitin-dependent proteolysis may contribute to aggregation events, which underlie the pathogenesis of several major human neurodegenerative diseases.

Alzheimer Disease↗
PubMed2000

Inhibition of the ubiquitin-proteasome system in Alzheimer's disease.

Alzheimer's disease is the most common cause of dementia in the elderly. Although several genetic defects have been identified in patients with a family history of this disease, the majority of cases involve individuals with no known genetic predisposition. A mutant form of ubiquitin, termed Ub(+1), has been selectively observed in the brains of Alzheimer's patients, including those with nonfamilial Alzheimer's disease, but it has been unclear why Ub(+1) expression should be deleterious. Here we show that Ub(+1) is an efficient substrate for polyubiquitination in vitro and in transfected human cells. The resulting polyubiquitin chains are refractory to disassembly by deubiquitinating enzymes and potently inhibit the degradation of a polyubiquitinated substrate by purified 26S proteasomes. Thus, expression of Ub(+1) in aging brain could result in dominant inhibition of the Ub-proteasome system, leading to neuropathologic consequences.

Alzheimer Disease↗
PubMed1998

Economic evaluation of programmes aiming at eradicating infectious diseases.

The subject of this article is to discuss the global and regional economic aspects of programmes for eradicating infectious diseases. The perspective on the issue is that scarce health care resources should be employed in the best possible way. The task is then to examine what the best possible use might be. A starting point is by asking the relevant policy questions attached to eradications: Is there a suitable technique, what are the costs, and what are the benefits? Of particular importance is the opportunity cost of using resources on eradication when other health care problems may require more urgent donation of resources. The paper attempts to set up a generic model for economic evaluation of eradication programmes. But, as there are many different treatment strategies varying from one country to another, such a generic model may need modifications to suit a particular strategy. However, the paper is contextual and should only be viewed as guidance for those wishing to conduct an economic analysis of eradication programmes, or as a initiative to create discussion among health care decision makers.

Communicable Disease Control↗
PubMed1997

Overexpression of bcl-2 alters usage of mutational hot spots in germinal center B cells.

Bcl-2 is an anti-apoptotic gene important in B cell development. In order to study how apoptosis regulates somatic hypermutation and selection of B cell clones in the germinal center, we examined the antibody response to phosphorylcholine (PC) in transgenic mice overexpressing bcl-2 in the B cell compartment. The anti-PC antibody response is dominated by the S107V1 variable region heavy chain gene. We, therefore, analyzed S107V1-encoded heavy chains from germinal center cells. The proportion of germinal center sequences that were mutated, and the frequency of mutations did not differ significantly between the two groups of mice. No significant differences were found in the clustering of replacement mutations in the complementarity determining regions (CDRs) and in replacement to silent (R:S) mutation ratios. A significant difference between bcl-2 transgenic mice and controls, however, was found in the targeting of mutations to oligonucleotide motifs presumed to be mutational "hot spots." While non-transgenic mice displayed the expected clustering of mutations in hot spots, mutations from bcl-2 transgenic mice lacked this pattern. This observation suggests that the mechanism for somatic hypermutation includes two distinct functions, a non-specific mutational apparatus and a mechanism to target mutation to hot spots, and that in certain circumstances these functions may be uncoupled.

Amino Acid Sequence↗
PubMed1997

The Danish approach to standards for economic evaluation methodologies.

Standards for economic evaluation have now been proposed in several countries. The background for this article is a report commissioned in 1994 by the Danish health authorities (the National Board of Health and the Danish Ministry of Health) on the state of the art of economic evaluation: are the methods ready to be used for systematic decision-making in the Danish healthcare sector? The themes of this article are the attitude towards economic evaluation of medical technologies and healthcare services in Denmark, the areas for application and the desirability and feasibility of a standard set of methods for conducting economic evaluations. In addition, the current state of methodologies in economic evaluation is briefly outlined. On the background of a roundtable discussion of interested parties, the Danish health authorities have decided to introduce economic evaluation of new pharmaceutical products, on a voluntary basis for 2 to 3 years, when application has been made for public reimbursement.

Denmark↗
PubMed1996

High serum IgA concentrations in patients with diabetes mellitus: agewise distribution and relation to chronic complications.

In this study we investigated the agewise distributions of serum IgA concentrations in 1251 type 1 and 2224 type 2 diabetic patients, and the association between serum IgA concentration and diabetic complications (retinopathy, neuropathy, nephropathy, macroangiopathy, and hypertension). The IgA concentrations of all groups of diabetic patients were significantly higher than those of the corresponding subgroups of 943 control subjects, except for type 1 patients >60 years of age. High IgA concentrations were found in 23.1% of the whole diabetic group. The prevalence of high IgA was significantly greater in males than in females among type 1 patients (24.4% vs 18%). In conclusion, an increase in circulating IgA concentrations is a generalized phenomenon among diabetic patients; IgA concentrations above the reference range are more common among male than female diabetics; and diabetic complications are associated with a significant increase in serum IgA concentration.

Adolescent↗
PubMed1994

The role of economic appraisal in Denmark.

The numbers of economic appraisals conducted have been increasing during the last ten years in Denmark. This article involves 17 economic appraisals on specific health issues. Most of the studies use the cost-effectiveness approach. Cost appraising has only been conducted in five of the studies, three use the cost-benefit approach, and only one uses the cost-utility approach. Most of the studies have been directed at the policy level and only five have been directed at the clinical decision making level. The success of the individual economic appraisals is being assessed by looking at their ability to change behaviour among the decision makers according to the results obtained and by looking at their ability to enter the decision making process. However, as this article stresses, economic appraisals have also been used to introduce the economic appraisal approach as a way of thinking, as a road to efficiency, within the health services. This has led to the incorporation of economic appraisals into committee work at the National decision making level, the issuing of guidelines to local health authorities including efficiency, and to some acceptance of the efficiency term among health professionals.

Clinical Competence↗
PubMed1991

Hospital comparisons using a Euro Health Data Base for resource management and strategic planning.

A European approach for resource management and strategic planning has been implemented in the HOSCOM project of AIM by defining information standards needed across countries, as well as a methodology to measure resources and costs at the institutional and interinstitutional level. A Euro Health Data Base (EHDB) has been obtained in order to test data availability and comparability as well as to validate models through macrocomparisons using case-mix (DRG's, refined grouping, disease staging) and microcomparisons based on three diseases (cardiac valve replacement, diabetes mellitus and hip fracture). The EHDB's presently based on 274 164 medical record summaries sampled from 7 countries allowed us to build prototypes (using Clipper, Prolog and SQL) in order to export uniform aggregates in the different countries, with standard software tools for statistical comparisons. It showed the present feasibility of using case-mix based on the European Minimum Basic Data Set (MBDS) and the difficulty of obtaining uniform data on resources and costs other than length of stay across countries. Medical data confidentiality was assured but not yet population-based representativity. Given the present state of the EHDB, problems have been clearly identified in order to be solved by international research and development projects in the near future.

Abstracting and Indexing↗
PubMed1990

[Costs and cost analysis].

The costs of an activity is frequently the most conspicuous part in decision making when changes in health care services are considered. It is thus essential to be aware of the principles and considerations underlying the composition of costs. The concept of cost is not restricted to expenditures that have to be paid. It involves the notion of opportunity cost i.e. the cost of a service is the satisfaction or benefit foregone in not being able to use the resources involved to obtain some other service which is also desirable and therefore also provides satisfaction. Strictly, this relates to the best alternative way of using the resources. In order to estimate the costs of an activity, all costs, whether direct or indirect, tangible or intangible, ought to be taken into account. The fact that they may be difficult to measure a value is no excuse for ignoring them. In a cost analysis the result has to be assessed in the light of the types of costs employed and the aim of the analysis. Average cost is very often used, but is seldom the relevant costs. What is normally of concern is the cost of some change. Only by using marginal costs i.e. those costs that actually do change is it possible to obtain a true picture of resource consequences of that change. Regardless of the type of cost it is necessary to consider on whom the costs fall and to whom the benefits accrue. These may not be the same.

Costs and Cost Analysis↗
PubMed1990

[The value of life and limb].

Assessment of the value of life and limbs is a controversial subject, not only emotionally but also theoretically. The economic starting point is based on assessment of the value of reduction or increase of the probability for an event which leads to disability or death. No concern is expressed for the single individual but for the phenomenon of probability where the person or persons who are affected by an event cannot be identified. Assessment of the value is in monetary units. The obvious discrepancy between the expression "value of life and limbs" and the theoretical content of the analysis has involved many misunderstandings. Attempts are made to elucidate and explain these. There is e.g. another method of assessing the value of life and limbs, the human capital method. In this, the disability and the premature death (compared with the current time) by means of loss of occupational income are assessed. The method is criticized and is discarded on the basis of theoretical arguments and consequences, the calculations of which are employed. Unfortunately, it has proved tempting to employ the method because it is relatively easy to make the calculations. Finally, the parts played by some recent questionnaire methods for assessment of alterations of risks are discussed. Assessment of the value of alterations in risks is an important requirement in order to carry out relevant cost-benefit analyses in the health sector. In cases where this is not possible, these analyses are meaningless.

Cost-Benefit Analysis↗
PubMed1990

[A review of the types of economic analyses of the health economy].

Great confusion is involved concerning health economics analyses. For example: What is the difference between cost-benefit and cost-effectiveness analyses? Is there a difference between the so-called cost-of-illness analyses? What is a financial analysis? These questions are discussed on the basis of the underlying economic theory and the use of the analyses. In order to avoid terminological confusion, the English terminology is retained. Cost-benefit and cost-effectiveness analyses are social economical analyses because they are all-embracing as regards what is understood by costs and profits based on the so-called welfare economy where cost-benefit analyses are concerned. The theoretical basis for cost-effectiveness analysis is slightly more obscure. Where both forms of analysis are concerned, no concern is shown for who obtains the profits or who pays the costs, i.e. a cross-sectional perspective. The financial analysis contrasts with this because attention is focussed directly on expenditures and revenues and the accounts responsible for the expenses and which obtain the revenues. The cost-of-illness analysis is a confusing but frequently employed and quoted form of analysis where an attempt is made to calculate the costs of a certain disease or injurious agent (alcohol, tobacco, accidents) for the various parties involved. These are subdivided into direct costs, roughly corresponding to the costs of treatment and indirect costs which include e.g. loss of income resulting from the illness, disability or death. This form of analysis is strongly warned against as the results of analysis may easily be misused frequently with absurd implications.

Cost-Benefit Analysis↗
PubMed1990

[What is cost effectiveness analysis?].

Cost-effectiveness analysis (CEA) is an established economical form of analysis which, in public services, replaces the marketing mechanism. The questions which CEA attempts to answer are: Which form of medical technology is most economically effective where a given disease is concerned. Where and how must the medical technology be commenced. Which group of patients can benefit from a given form of medical technology? It is a prerequisite for employment of CEA that there is unanimity in advance about the object of an activity, eg. a given treatment or procedure in the diagnostic investigation. Several strategies may be employed to ensure that the aim is sufficiently wide: the limits may be explicit; goals may be established which compare years of life with quality of life, or several goals may be present in the goal. The predominant economical expression in CEA is alternative costs which must be sacrificed in order to carry out a certain activity. In order to estimate what is obtained by carrying out an activity, an expression of effect is essential. These are most frequently both of quantitative and also of qualitative character and may be subdivided into three categories: Alterations in the employment of resources. Alterations in production by society. Alterations in the conditions of health of the individual. Doctors are important decisions-makers and distributors of resources in the health services. The questions which a CEA can provide graduated answers to, are the questions that the doctor works with in clinical practice.(ABSTRACT TRUNCATED AT 250 WORDS)

Cost-Benefit Analysis↗