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Biomedical subjects

U Persson

Publications and source records attributed to U Persson.

At least 19 recordsLinked to original sources
PubMed2005

Costs associated with blood transfusions in Sweden--the societal cost of autologous, allogeneic and perioperative RBC transfusion.

Anaemia is characterised by an insufficient number of red blood cells (RBCs) and might occur for different reasons, e.g. surgical procedures are often with associated blood loss. Patients who suffer from anaemia have the option of treatment with blood transfusion or medical treatment. In this study, the societal cost, for the case of Sweden, of RBC transfusion using three different techniques, i.e. allogeneic, autologous and intraoperative transfusion, was estimated. The analysis was based on information from interviews with hospital staff at large Swedish hospitals and from published data. The average cost for a 2 units transfusion was found to be Swedish kronor (SEK) 6330 (702 Euro) for filtered allogeneic RBCs and SEK 5394 (598 Euro) for autologous RBCs for surgery patients. Transfusion reactions accounted for almost 35 per cent of the costs of allogeneic RBC transfusions. The administration cost was found to be much higher for autologous transfusions compared with allogeneic transfusions. The cost of intraoperative erythrocyte salvage was calculated to be SEK 2567 (285 Euro) per transfusion (>4 units).

Anemia↗
PubMed2005

Alport syndrome in southern Sweden.

AIM: The aim of the present investigation is to study the epidemiology of Alport syndrome in southern Sweden, to search for mutations in the COL4A5 gene and to estimate the mutation frequency. PATIENTS AND METHODS: Patients with suspected Alport syndrome were identified in an area with a population of 1.45 million. Clinical criteria were used to establish the diagnosis and samples for mutation analysis were collected. Mutation analyses were performed with Single-Stranded Conformation Polymorphism analysis (SSCP) of PCR-amplified genomic DNA. RESULTS: Altogether 25 families with hereditary nephritis were identified. Alport syndrome with X-linked transmission was evident in 14 families, with juvenile (< 31 years) progression to end-stage renal failure (ESRF) in ten, and adult (> or = 31 years) in four families. CONCLUSION: The frequency of males with X-linked disease was calculated to one in 17,000 male births (95% confidence interval (CI) 1/10,500-1/28,600), and the prevalence to one in 40,000. A total of seven females with ESRF were identified, with a median age at ESRF of 45 years. The male to female ratio of cases with ESRF was 4.9 to 1. The risk of developing ESRF among females was from the expected incidence roughly estimated to 12%. Patients with X-linked disease constituted 1.8% of patients with ESRF in the examined area. A mutation was identified positive in 10 of 14 families with X-linked disease, but never in families not fulfilling the clinical criteria for Alport syndrome. In families with juvenile phenotype and positive mutation analysis, the mutation frequency was calculated to between 1/78,000 and 1/198,000 (95% CI 1/42,000-1/177,000) if the effective fertility was estimated to be between 0 and 0.2.

Adolescent↗
PubMed2003

Cost-effectiveness analysis of inhaled corticosteroids in asthma: a review of the analytical standards.

PURPOSE: To determine whether published cost-effectiveness studies on inhaled corticosteroids (ICS) in asthma adhered to basic analytical standards as defined in health economic textbooks and in guidelines assessing and comparing efficacy and safety. METHODS: Original cost-effectiveness studies published between 1990 and 2000 in general medical or economic journals were reviewed to assess the adherence to five fundamental methodological principles: (1) design of the study, (2) choice of perspective and corresponding costs, (3) choice of outcome measure, (4) marginal cost analysis, and (5) sensitivity analysis and discussion about external validity. For each principle, the studies were ranked as high, medium or low quality. RESULTS: Most of the 18 studies included were ranked medium on the first two principles. The studies adhered to a higher degree to the remaining three principles. Only three studies were high ranked in all five principles. The number of principles fulfilled increased over time. Studies comparing pharmaceutical products from competing companies were typically short-term studies, designed for other purposes than health economic analyses, and, in general, did not use therapeutically equivalent dosing. CONCLUSIONS: Attention should be drawn to the study design, the weak correspondence between perspective and costs, and especially to the impact of bias in health economic results when comparing different doses of ICSs.

Administration, Inhalation↗
PubMed2002

Costs for screening, intervention and hospital treatment generated by the Malmö Preventive Project: a large-scale community screening programme.

OBJECTIVES: The purpose of this study was to estimate retrospectively the costs of health care resources used in the Malmö Preventive Project, Sweden and estimate the costs of in-patient care that were avoided because of early intervention. SETTING AND SUBJECTS: A large-scale community intervention programme was conducted from 1974 to 1992 in Malmö, Sweden with the aim of reducing morbidity and mortality of cardiovascular diseases (CVD), alcohol related illnesses, and breast cancer. Between 1974 and 1992, 33 336 male and female subjects were screened for hypertension, hyperlipidaemia, type-2 diabetes and alcohol abuse. Intervention programmes that included life-style modifications, follow-up visits with physicians and nurses and drug therapy were offered to about 25% of screened subjects. METHODS: Recruitment costs were generated through out the screening period. Intervention costs were estimated for 5 years after screening. Excess in-patient care costs were estimated by subtracting hospital consumption for an unscreened, matched cohort from that of the screened cohort over follow-up periods of 13-19 years. Intervention and excess in-patient care costs were estimated until 1996. RESULTS: The net expenditures for recruitment and intervention was SEK253 million and saved costs for in-patient care of SEK143 millions (1998 prices). Considering the opportunity cost of the resources used in the study, the net cost rises to about SEK200 millions. CONCLUSIONS: The results suggest that only part of the intervention costs were offset by reduction in future morbidity health care costs. This is in line with results from prospective analyses of other primary prevention programmes.

Adult↗
PubMed2002

Cost-effectiveness of treating deep diabetic foot ulcers with Promogran in four European countries.

OBJECTIVE: This study aimed to estimate the cost-effectiveness of treating non-superficial diabetic foot ulcers with Promogran plus good wound care (GWC) compared with GWC alone in four European countries (France, Germany, Switzerland and UK). METHODS: An existing Markov-based health economic model of non-superficial diabetic foot ulcers was adapted to incorporate the relative efficacy of Promogran compared with GWC alone as demonstrated in a randomised controlled trial. Treatment with Promogran was modelled for a maximum of three months. Country-specific treatment costs were used to estimate the incremental cost per ulcer-free day gained over 12 months. Some parameter assumptions were changed to assess the sensitivity of the results. RESULTS: Within the first three months of treatment, 26% of ulcers in the Promogran cohort healed compared with 20.7% in the GWC cohort. Over the 12 months, the average number of months spent in the healed state was 3.41 (GWC) and 3.75 (Promogran). Promogran treatment was found to be cost-saving in all four countries, using year 2000 Euro values. CONCLUSION: Promogran with GWC may be cost-effective, perhaps even cost-saving, under a wide variety of assumptions for the treatment of neuropathic foot ulcers. DECLARATION OF INTEREST: This study was funded by Ethicon Gmbh (Johnson and Johnson), Germany.

Bandages↗
PubMed2001

Detection of mutations in the COL4A5 gene by SSCP in X-linked Alport syndrome.

Alport syndrome is a progressive renal disease leading to chronic renal failure, which often is accompanied by sensorineural deafness and ophthalmological signs in the form of anterior lenticonus. The X-linked form of the disease is caused by mutations in the COL4A5 gene encoding the alpha5-chain of type IV-collagen. We performed mutation analysis of the COL4A5 gene by PCR-SSCP analysis of each of the 51 exons with flanking intronic sequences in 81 patients suspected of X-linked Alport syndrome including 29 clear X-linked cases, 37 cases from families with a pedigree compatible with X-linked inheritance, and 15 isolated cases. We found a mutation detection rate of 52% (42/81) (58% in males and 21% in females), and 69% (20/29) in families who clearly demonstrated X-linked inheritance. Thirty-six different mutations were found in 42 patients comprising 16 missense mutations, seven frameshifts, three in-frame deletions, four nonsense mutations, and six splice site mutations. Twenty-two of the mutations have not previously been reported. Furthermore, we found one non-pathogenic amino acid substitution, one rare variant in a non-coding region, and one polymorphism with a heterozygosity of 28%. Three de novo mutations were found, two of which were paternal and one of maternal origin.

Codon, Nonsense↗
PubMed2001

Scope and scale insensitivities in a contingent valuation study of risk reductions.

A contingent valuation study asking willingness to pay (WTP) for reducing the overall death risk as well as the risk for fatal and non-fatal injuries in road traffic accidents was performed in Sweden 1998. Different sub-samples were used to test for scale (different risk reductions) and scope (different outcomes) effects, existence of which implies that a respondent is capable of differentiating a WTP-answer accordingly. The results indicated that respondents needed some reference point for their valuation. For instance, dependent samples showed, contrary to independent ones, a significant difference between WTP of dying from any cause and in a traffic accident for the same relative but different absolute risk reduction. Regarding non-fatal traffic accidents, tests were performed comparing valuation of risk reductions for injuries with different outcomes but identical baseline risks and relative risk reductions. Similar to the case above, dependent samples differentiated their WTP and were willing to pay significantly more for a severe injury than for a slight one, which was not the case for independent samples.

Accidents, Traffic↗
PubMed2001

Cost effectiveness of Becaplermin in the treatment of diabetic foot ulcers in four European countries.

OBJECTIVE: The primary objective of this study was to estimate the cost effectiveness of treating diabetic foot ulcers with becaplermin (Regranex) plus good wound care (GWC) compared with GWC alone in a variety of European healthcare settings. A secondary objective was to analyse the effect of different treatment practices on the economics of caring for diabetic foot ulcers. DESIGN AND SETTING: Markov-based simulation study from the perspective of a national health system. METHODS: A 12-month Markov computer simulation model was used to assess the cost effectiveness in 4 European countries of treating diabetic foot ulcers with becaplermin plus GWC versus GWC alone. Transition probabilities were taken from a prospective study of 183 patients and becaplermin efficacy was based on 20-week healing rates in a recent meta-analysis of clinical trials involving 449 patients. Country-specific treatment cost data were collected in collaboration with local economic consultations and combined with the disease model to estimate the incremental cost per ulcer-free month gained. The model was then run using hypothetical low- and high-intensity resource usage profiles to investigate the economics of caring for diabetic foot ulcers. RESULTS: Over the course of 1 year, individuals who received becaplermin plus GWC were, on average, predicted to spend an additional 0.81 months (24% longer) free of ulcers and to experience a 9% lower risk of undergoing a lower extremity amputation than individuals who received GWC alone. Consequently, becaplermin plus GWC was estimated to be net cost saving in Sweden, Switzerland and the UK. In France, the addition of becaplermin was estimated to add $US19 (1999 values) for each additional ulcer-free month gained. There were substantial intercountry differences in treatment practices and the costs of treating diabetic foot ulcers. CONCLUSIONS: Becaplermin may be a cost-effective treatment for neuropathic diabetic foot ulcers in a wide range of European settings. In Sweden, Switzerland and the UK, becaplermin may even be cost saving. Substantial intercountry differences in resource patterns appear, at least partly, to be the logical outcome of differences in unit costs.

Becaplermin↗
PubMed2000

Activated protein C-protein C inhibitor complex formation: characterization of a neoepitope provides evidence for extensive insertion of the reactive center loop.

Protein C inhibitor, a serine proteinase inhibitor (serpin), is the physiologically most important inhibitor of activated protein C. We have made a monoclonal antibody (M36) that binds with equally high affinity to an epitope present in activated protein C-protein C inhibitor complexes and cleaved loop-inserted protein C inhibitor. Insertion of a synthetic N-acetylated tetradecapeptide (corresponding to residues P1-P14 of the reactive center loop) into beta-sheet A of the uncleaved inhibitor also exposed the epitope. The antibody had no apparent affinity for native uncleaved inhibitor or for the free peptide. Synthetic P1-P14 analogues, with Arg P13 or Ala P9 substituted to the residues found in mouse protein C inhibitor (Thr and Ile, respectively), were also inserted in beta-sheet A. The Arg P13/Thr substitution led to a greatly impaired reactivity with the antibody, whereas the Ala P9/Ile mutation resulted in a modest loss of reactivity with the antibody. These results indicate that complex formation leads to insertion of the reactive center loop in beta-sheet A from Arg P14 and presumably beyond Ala P9. Moreover, to the best of our knowledge, this is the first instance where the neoepitope of a complexation-specific monoclonal antibody has been localized to the loop-inserted part of beta-sheet A, the part of the serpin where the complexation-induced conformational change is most conspicuous.

Animals↗
PubMed2000

Identification and purification of vitamin K-dependent proteins and peptides with monoclonal antibodies specific for gamma -carboxyglutamyl (Gla) residues.

Novel monoclonal antibodies that specifically recognize gamma-carboxyglutamyl (Gla) residues in proteins and peptides have been produced. As demonstrated by Western blot and time-resolved immunofluorescence assays the antibodies are pan-specific for most or all of the Gla-containing proteins tested (factors VII, IX, and X, prothrombin, protein C, protein S, growth arrest-specific protein 6, bone Gla protein, conantokin G from a cone snail, and factor Xa-like proteins from snake venom). Only the Gla-containing light chain of the two-chain proteins was bound. Decarboxylation destroyed the epitope(s) on prothrombin fragment 1, and Ca(2+) strongly inhibited binding to prothrombin. In Western blot, immunofluorescence, and surface plasmon resonance assays the antibodies bound peptides conjugated to bovine serum albumin that contained either a single Gla or a tandem pair of Gla residues. Binding was maintained when the sequence surrounding the Gla residue(s) was altered. Replacement of Gla with glutamic acid resulted in a complete loss of the epitope. The utility of the antibodies was demonstrated in immunochemical methods for detecting Gla-containing proteins and in the immunopurification of a factor Xa-like protein from tiger snake venom. The amino acid sequences of the Gla domain and portions of the heavy chain of the snake protein were determined.

1-Carboxyglutamic Acid↗
PubMed1999

C3 and C4 allotypes in anti-neutrophil cytoplasmic autoantibody (ANCA)-positive vasculitis.

In ANCA-associated small vessel vasculitis few genetic factors have proven to be of importance for disease susceptibility, an exception being deficiency of alpha1-anti-trypsin, the main inhibitor of proteinase 3 (PR3). Alerted by our finding that myeloperoxidase has affinity for C3, and the finding of an increased frequency of the C3F allele in systemic vasculitis in a British cohort, we examined polymorphism of C3 and C4 in patients with ANCA+ small vessel vasculitis. After identification of all patients at our department with a positive ANCA test during the period 1991-95 and a diagnosis of small vessel vasculitis, blood samples were collected after informed consent. The 67 included patients were grouped according to ANCA serology and disease phenotype using the Chapel Hill nomenclature. The gene frequency of C3F was found to be increased (0. 32) compared with controls (0.20; P < 0.05) in the PR3-ANCA+ subgroup. The frequency of C4A3 was increased in the group as a whole, but no increase of C4 null alleles was seen. The findings imply a role for the complement system in the pathogenesis of ANCA-associated small vessel vasculitis.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1999

Cost-effectiveness analysis of pegylated-liposomal doxorubicin and liposomal daunorubicin treatments in patients with Kaposi's sarcoma.

Economic evaluations of new AIDS treatment drugs are important. For physicians treating patients with Kaposi's sarcoma, these issues are especially meaningful since cancer treatment costs for this group of patients are high. Kaposi's sarcoma is the most frequently occurring neoplasm in AIDS patients, affecting about 15% of this population. In our study, a retrospective economic evaluation has been made based on data from two randomized phase III clinical studies of severely immune-compromised HIV-infected individuals and which compares liposomal doxorubicin with liposomal daunorubicin. We have estimated the cost and cost effectiveness of the two drugs. The costs per complete or partial response are USS 18340 for daunorubicin and USS 8871 for doxorubicin. The incremental cost per additional responder by using liposomal doxorubicin instead of liposomal daunorubicin is USS 1910. Sensitivity analysis shows that these results hold over a wide range of assumptions.

Antibiotics, Antineoplastic↗
PubMed1999

The economics of preventing revisions in total hip replacement.

We showed that the selection of a cost-effective type of cement and method of prophylaxis against deep infections for patients undergoing total hip replacement depended on the number of arthroplasties performed each year at individual hospitals. When 100 arthroplasties were performed each year, the use of Palacos cement and systemic antibiotics reduced the total costs to the department, i.e., the cost of cement, infection prophylaxis and revisions. The use of gentamicin-impregnated cement in combination with systemic antibiotics will further reduce the risk of revision and is another cost-effective strategy. The most effective infection prophylaxis would be achieved with a combination of gentamicin-impregnated cement, systemic antibiotics and surgical enclosure. However, the additional cost of the surgical enclosure would not be offset by cost savings due to reduced risk of revisions.

Anti-Bacterial Agents↗
PubMed1999

Expression of TGF-beta related Smad proteins in human epithelial skin tumors.

Members of the transforming growth factor (TGF)-beta family regulate cell growth and differentiation activating intracellular Smad proteins. Their role in skin and skin tumorigenesis is not well understood. Therefore we investigated the expression of TGF-beta type I receptor (TbetaR-I) and Smad-proteins involved in the TGF-beta-pathway, e.g. Smad2, Smad3, Smad4, Smad6 and Smad7. We examined the effects of TGF-beta1, -beta2, BMP2, BMP7 on five epithelial cell lines in vitro. TGF-beta1-mediated growth inhibition of HaCaT and HSC4 were observed with half maximal effects at approximately 7 pg ml-1 and 20 pg ml-1, respectively. However, malignant HSC2 and A431 cells were unresponsive to TGF-beta1. A differentiation was seen after 5 days in HaCaT and HSC4 cells only. We compared the reactivity with specific antisera against TbetaR-I and Smad proteins among the different skin tumors: seborrheic keratoses (SK), actinic keratoses (AK), basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). There were statistically significant differences of the ratio between the expression in tumor and that in non-tumorous epithelial cells in each tissue specimen. There was a tendency for the lower level of TbetaR-I expression of SCC compared with SK (p=0.08). This was accompanied by the decreased expression of the TbetaR-I. We found a markedly decreased expression of all antigens in BCC. conversion of normal keratinocytes to tumorigenic cells may in part be due to an acquisition of resistance to TGF-beta and loss of expression of intracellular signalling Smad proteins.

Activin Receptors, Type I↗
PubMed1998

The L45 loop in type I receptors for TGF-beta family members is a critical determinant in specifying Smad isoform activation.

Transforming growth factor-beta (TGF-beta) and bone morphogenetic proteins (BMPs) signal via distinct type I and type II receptors and Smad proteins. A nine amino acid sequence between kinase subdomains IV and V in type I receptors, termed the L45 loop, has been shown to be important in conferring signalling specificity. We examined the responses of a mutant TGF-beta type I receptor (TbetaR-I) and a mutant BMPR-IB, in which the L45 regions of these two receptors were exchanged. Swapping the four amino acid residues that are different in BMPR-IB for those in TbetaR-I, and vice versa, switched their type I receptor-restricted Smad activation and specificity in transcriptional responses. These studies identify the L45 loop regions in type I receptors as critical determinants in specifying Smad isoform activation.

Amino Acid Sequence↗