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Biomedical subjects

F Wisløff

Publications and source records attributed to F Wisløff.

At least 19 recordsLinked to original sources
PubMed2001

The evaluation of clotting times in the laboratory detection of lupus anticoagulants.

Although there is international consensus regarding the general principles of testing for lupus anticoagulants (LAs), no agreement exists as far as the analysis of the clotting time results is concerned. Twenty-nine laboratories participating in the Fifth International Survey of Lupus Anticoagulants (ISLA-5) reported the activated partial thromboplastin time (APTT)-based clotting times obtained on seven defined test samples and a normal plasma (NP) using the same two reagents with low and high phospholipid (PL) concentrations, respectively. These clotting times were used to analyse how various methods of calculating the results may influence the apparent sensitivity of LA tests. We found that the use of a separate screening test may lead to the exclusion of samples where the presence of LA would have been detected by a combined screening and confirmatory method. For instance, the dilute APTT (dAPTT) gave a sensitivity of 53.5% (screening test), while the calculation of a ratio between the clotting times obtained with two different PL concentrations gave a sensitivity of 68.1% (confirmatory test). The normalisation of results by dividing with the corresponding results of NP increased the apparent sensitivity. The screening test ratio between dAPTT results of test samples and NP gave a sensitivity of 84.7%. The normalised ratio between the clotting times obtained with the two reagents (lupus ratio, LR) gave a sensitivity of 95.1%. We conclude that when testing for LA, all samples should be tested with both low (screening procedure) and high (confirmatory procedure) PL concentrations. These two clotting times should be evaluated in relation to each other and to the corresponding results obtained with a reference plasma (normalisation).

Blood Coagulation Tests↗
PubMed2001

[High dose therapy with autologous stem cell support--finally a progress in myelomatosis].

BACKGROUND: Since the introduction of the simple cyclic oral treatment with melphalan and prednisone in the late 1960s, there has been no substantial improvement in the therapy of multiple myeloma. In 1994, the Nordic Myeloma Study Group initiated a population-based, prospective study to evaluate the impact on survival of high dose chemotherapy in newly diagnosed, symptomatic patients under 60 years of age, compared to a conventionally treated control group. MATERIAL AND METHODS: 274 patients were treated according to a specified high dose protocol and compared to 274 patients from previous population-based trials fulfilling the same eligibility criteria. RESULTS: Median survival was 44 months in the control group and 62 months in the intensive treatment group (risk ratio 1.65; 95% CI = 1.28-2.14, P = 0.0001). A study of health-related quality of life (HRQoL) which was integrated in the trial showed a moderately reduced HRQoL associated with the intensive treatment phase, but no statistically significant difference beyond the first year of follow-up. In a cost-utility analysis of the trial, the cost per (quality-adjusted life years) was estimated at USD 26,000. INTERPRETATION: The incremental cost of the treatment is within what is usually thought to be acceptable limits. Further improvement of the results and reduction of stay in hospital would give an even more favourable cost-utility ratio.

Adult↗
PubMed2001

Cost-utility analysis of high-dose melphalan with autologous blood stem cell support vs. melphalan plus prednisone in patients younger than 60 years with multiple myeloma.

We evaluated the costs and the cost utility of high-dose melphalan and autologous stem cell support followed by interferon maintenance relative to conventional treatment with melphalan and prednisone, in patients less than 60 yr of age with multiple myeloma. From March 1994 to July 1997, 274 patients with newly diagnosed, symptomatic multiple myeloma were enrolled in a prospective, non-randomized, population-based, multicenter study to evaluate the treatment with high-dose melphalan and autologous blood stem cell support. Health-related quality-of-life was measured prior to treatment and during follow-up, using the EORTC QLQ-C30 questionnaire. Resource consumption was also recorded prospectively. The intensive treatment yielded a significant increase in median survival time from 44 to 62 months compared to conventionally treated patients. The corresponding gain in quality-adjusted life years (QALY) was found to be 1.2. Cost per QALY gained by the treatment with high-dose melphalan and autologous blood stem cell support was estimated at NOK 249,000 (USD 27,000).

Cost-Benefit Analysis↗
PubMed2001

Health-related quality of life in multiple myeloma patients receiving high-dose chemotherapy with autologous blood stem-cell support.

In a population-based study, the Nordic Myeloma Study Group found a survival advantage for high-dose melphalan with autologous blood stem-cell support compared to conventional chemotherapy in myeloma patients under 60 yr of age (risk ratio: 1.62; confidence interval [CI] 1.22-2.15; p = 0.001). A study of health-related quality of life (HRQoL) was integrated in the trial, using the EORTC QLQ-C30 questionnaire. Of the 274 patients receiving intensive therapy 221 (81%) were compared to 113 (94%) of 120 patients receiving conventional melphalan-prednisone treatment. Prior to treatment, there were no statistically significant differences in any HRQoL score between the two groups. One month after the start of induction chemotherapy, the patients on intensive treatment had more sleep disturbance than the control patients. At 6 mo, corresponding to a mean of 52 d after high-dose melphalan, the patients on intensive treatment had moderately lower scores for global QoL and role and social functioning and there was also a significantly higher score for appetite loss. At 12 and 24 mo, the HRQoL was similar to that of the control patients. At 36 mo, there was a trend toward less fatigue, pain, nausea, and appetite loss in the intensive-treatment group. Thus, the 18 mo of prolonged survival seem to be associated with a good health-related quality of life. Despite the moderate HRQoL reduction associated with the early intensive chemotherapy phase, this treatment modality must be regarded as an important step forward in the care of multiple myeloma.

Adult↗
PubMed2000

Health-related quality of life and patients' perceptions in interferon-treated multiple myeloma patients. Nordic Myeloma Study Group.

The effect of interferon on the health-related quality of life in multiple myeloma was assessed in two trials carried out by the Nordic Myeloma Study (Group (NMSG). In both trials, the EORTC QLQ-C30 questionnaire, supplemented with 11 items relating to interferon toxicity, was used. The first was a randomized controlled trial (NMSG 4/90) evaluating the addition of interferon alpha-2b to melphalan and prednisone during induction, maintenance and relapse. During the first 12 months, patients on interferon reported more chills, fever, fatigue, pain, nausea/vomiting, appetite loss and dry skin than the control patients, and a slight reduction of global health and quality of life. From 12 months onward there were no significant differences in any score between the two groups. In a later trial (NMSG 5/94) evaluating the effect of high-dose chemotherapy with stem cell support in patients under 60 years of age with newly diagnosed myeloma, interferon was used as maintenance. During the maintenance phase, symptom and toxicity scores were not significantly different from those in control patients under 60 years of age in the previous trial. Thus, interferon appeared to be well tolerated after high-dose chemotherapy with stem cell support.

Adult↗
PubMed2000

The Lupus Ratio test--an interlaboratory study on the detection of Lupus anticoagulants by an APTT-based, integrated, and semi-quantitative test. Fifth International Survey of Lupus Anticoagulants--ISLA 5.

The Lupus Ratio (LR) test for lupus anticoagulants integrates screening, mixing with normal plasma and confirmation procedures into one assay. The sensitivity and reproducibility of the APTT based version of this assay was tested in an interlaboratory study that was part of the Fifth International Survey of Lupus Anticoagulants (ISLA-5). One LA negative plasma containing heparin, six LA positive plasmas and a normal pooled plasma (NP) were distributed to 31 laboratories world-wide together with two APTT reagents, one with a high and one with a low phospholipid concentration. The laboratories performed two APTTs, one with each reagent, on 1:1 mixtures of test plasma and NP. The ratio between the two clotting times was divided by the corresponding ratio for the NP. This final ratio is the LR of that plasma. The overall sensitivity was found to be 95.1%, and the normal, heparin-containing sample was reported to be negative by all the laboratories. When the results were grouped in low, medium and high positive plasmas, a "consensus" regarding the strength of each plasma was easily found. 85.0% of the results were in agreement with this consensus. This study shows that with the LR test, it is possible to obtain high interlaboratory agreement regarding the presence or absence of LA as well as the semi-quantification of this inhibitor.

Anticoagulants↗
PubMed1999

Do antiphospholipid antibodies interfere with tissue factor pathway inhibitor?

This study was conducted to investigate whether antiphospholipid antibodies (APA) can interfere with the phospholipid-dependent inhibition of coagulation exerted by tissue factor pathway inhibitor (TFPI). Eleven patients with APA and eleven healthy controls matched for age and gender were enrolled. Blood samples were drawn before and 5 minutes after an intravenous injection of unfractionated heparin 5000 IE, which is known to cause TFPI release in healthy individuals. The preheparin samples showed significantly higher TFPI free antigen levels in the APA positive patients than in the controls (21.7 vs. 14.2 ng/ml, p = 0.03). TFPI activity as measured in a chromogenic substrate assay also was higher in patients, but this difference was not statistically significant (1.13 vs. 1.01 U/ml, p = 0.2). The TFPI levels showed a considerable rise in both patients and controls after heparin injection. In both assays, the postheparin levels were significantly higher in patients than in controls (TFPI antigen: 179 vs. 153 ng/ml, p = 0.05; TFPI activity: 3.26 vs. 2.51 U/ml, p = 0.03). A modified diluted prothrombin time assay (dPT) was used to measure TFPI anticoagulant activity. In this assay, samples from the patients with the strongest effect of lupus anticoagulants (LAs) on preheparin coagulation times showed little or no increase after heparin injection. This result may reflect an inhibition of TFPI anticoagulant activity by strong LAs. In conclusion, we have found that patients with APA have higher TFPI amidolytic activity/antigen level both before and after heparin stimulation of TFPI release. These observations do not explain the higher thrombotic risk in these patients but may reflect an upregulated tissue factor activity, which has been demonstrated in these patients. TFPI anticoagulant activity, however, as measured in a dPT assay, may be inhibited by strong LAs.

Adult↗
PubMed1999

Assessing the consistency of psychometric properties of the HRQoL scales within the EORTC QLQ-C30 across populations by means of the Mokken Scaling Model.

This paper demonstrates how the Mokken Scaling Model and other statistical tools may be useful in assessing the consistency of psychometric properties of health-related quality of life (HRQoL) scales across various populations. The main focus is the psychometric performance of the scales proposed for the EORTC QLQ-C30 in seven patient groups totalling more than 2,000 cancer patients. All scales performed satisfactorily in the total sample with the exception of the role functioning and cognitive functioning scales, which failed in terms of reliability and item discriminant validity. The descriptive statistics for the scales show that several of them, particularly those that build upon only two items, have discrimination problems at the extremes, visible in the high percentages at the maximum or the minimum observed values. The scalability analysis in the subsamples showed that the essential assumption in the Mokken Scaling Model of equal item step order does not hold for the cognitive functioning, emotional functioning and physical functioning scales. We conclude that the Mokken Scaling Model is well suited to the purpose of examining the generalizability of HRQoL scales across subpopulations although a global statistical test of the fit of the measurement model is not available.

Activities of Daily Living↗
PubMed1999

Development of an EORTC questionnaire module to be used in health-related quality-of-life assessment for patients with multiple myeloma. European Organization for Research and Treatment of Cancer Study Group on Quality of Life.

A multiple myeloma-specific quality-of-life questionnaire module has been designed in collaboration with the EORTC Quality-of-Life Study Group to be used in clinical trials with the EORTC QLQ-C30, a general cancer questionnaire. Strict methodology was employed to ensure thorough and appropriate development of the module. An extensive literature review was performed to identify health-related quality-of-life issues relevant to patients with multiple myeloma. Semi-structured interviews were then carried out in several European countries with health-care providers experienced in the treatment of patients with multiple myeloma, and with a group of patients with multiple myeloma, to identify the issues which were most important to patients. A questionnaire was devised from the list of issues, using a 1-week time-frame and response categories consistent with the EORTC QLQ-C30. The provisional questionnaire and the EORTC QLQ-C30 were administered to patients with multiple myeloma in each participating country with further semi-structured interviews to refine the content and design of the questionnaire. A review of the results obtained in each stage of development resulted in a 24-item myeloma-specific module, the EORTC QLQ-MY24, which assesses disease-specific symptoms and their impact on everyday life, treatment side-effects, social support, and future perspective. The module is currently undergoing further international field-testing to assess its psychometric properties.

Adult↗
PubMed1999

Therapeutic options in the treatment of multiple myeloma: pharmacoeconomic and quality-of-life considerations.

A review of current treatment options in multiple myeloma is presented, including data on health-related quality of life and pharmacoeconomics. For induction chemotherapy, no combination of cytostatic drugs has been shown to be consistently superior to the simple cyclic oral treatment with melphalan and prednisone that has been available for 30 years. The total resource consumption and direct costs per patient treated with melphalan and prednisone is approximately $US10,000 (1995 values). As median survival is prolonged from less than a year in untreated patients to 30 to 36 months, this treatment must be considered cost effective. Interferon-alpha has a modest effect on progression-free and overall survival when added to chemotherapy regimens. However, the high cost and toxicity of this drug results in an unfavourable cost-utility ratio, estimated to be between $US50,000 to $US100,000 per quality-adjusted life-year gained. Clinical trials suggest that high dose chemotherapy followed by autologous stem cell support administered to patients who have achieved disease stabilisation or objective response to conventional induction chemotherapy, prolongs median survival by about 1.5 years. Preliminary cost-utility analyses suggest a cost per life-year gained of $US30,000 to $US40,000. Further potential improvements of this therapeutic modality are under way. Several bisphosphonates have been tested for the ability to prevent the skeletal complications of multiple myeloma. Monthly infusions of pamidronate have been shown in 1 randomised trial to significantly reduce the rate of skeletal complications. Unfortunately, the rapid and widespread acceptance of this therapy seems to preclude further prospective, placebo-controlled trials with cost-utility evaluation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Hemostatic variables as independent predictors for fetal growth retardation in preeclampsia.

BACKGROUND: Preeclampsia is a major contributor to perinatal disease and fetal growth retardation (FGR). It has been suggested that increased intravascular coagulation, fibrin deposition in spiral arteries and hypoperfusion of the placenta are involved in these pregnancy complications. METHODS: Multiple variables of the hemostatic system and lipid metabolism, as well as clinical features, were entered into univariate and multivariate models in order to examine the association with preeclampsia and FGR. RESULTS: Two hundred women with preeclampsia and 97 normotensive pregnant women were examined. Plasma levels of the thrombin-antithrombin complex (TAT), tissue factor pathway inhibitor free antigen (TFPI-Fag), protein S free antigen, plasminogen activator inhibitor type-1 (PAI-1) activity and serum levels of triglycerides were significantly increased, whereas plasma levels of antithrombin (AT), fibrinogen, C4b-binding protein (C4b-BP), PAI-2 antigen and serum HDL-cholesterol levels were decreased in the presence of preeclampsia. In the multivariate regression analysis, high TFPI-Fag plasma levels were associated with the presence of preeclampsia. The presence of FGR was in the univariate analysis associated with decreased PAI-1 activity and lower concentrations of fibrin, fibrinogen, factor VII antigen and PAI-2 antigen, as well as with evidence of macroscopic placental infarction. In a multivariate regression model, low maternal weight, placental infarction and low PAI-2 levels were predictors for low birth weight. In a logistic regression model, with the presence or absence of FGR as the dependent variable, male sex of the infant, placental infarction, low PAI-1 activity and factor VII antigen or PAI-2 antigen levels were independent predictors. CONCLUSIONS: Our results are consistent with activated coagulation in the placental vessels in preeclampsia. A low concentration of PAI-2 antigen in plasma emerged as the most consistent risk factor for preeclampsia and FGR.

Adolescent↗
PubMed1997

[Measurement of health-related quality of life in malignant diseases. Does it have any consequences?].

The traditional end points of clinical trials in malignant disease are response, disease-free survival, and overall survival. Because a substantial part of cancer treatment is palliative, health-related quality of life should be a major objective in clinical trials. Cancer specific questionnaires, which measure the various quality of life domains and which are tested for reliability, validity and sensitivity to changes in clinical status, are now available. Measurement of health-related quality of life may lead to important conclusions. For instance, results from a Nordic myeloma trial suggest that obtaining an objective response is not a prerequisite for achieving an improved quality of life. They also indicate that the 5 to 6 month plateau phase prolongation obtained by giving interferon alpha-2b in addition to melphalan/prednisone is not associated with any quality of life benefit. Data from the same trial are used to illustrate how quality of life data can be utilized in cost-utility analysis: the cost per quality adjusted life year (QALY) gained by adding interferon was estimated at USD 110,000.

Antineoplastic Agents↗
PubMed1997

A simple procedure that increases the specificity of the activated protein C resistance test in samples containing antiphospholipid antibodies.

UNLABELLED: It is well known that plasmas with lupus anticoagulants (LA) may give false low activated protein C (APC) ratios, and these false positive tests are not necessarily corrected by mixing with factor V deficient plasma (FVdef). In the present study, we show that repeating the test after mixing 1 + 1 with pooled normal plasma (NP) instead of mixing with FVdef confirm the presence of the Leiden mutation (FV-Leiden) in patients with antiphospholipid antibodies (APA). Samples from sixteen patients with a low APC-ratio were examined. Eight samples contained APAs, including five samples with LA. RESULTS: The APC-ratios of eleven samples, including four with APAs, became normal when retested after mixing the plasma 1 + 1 with NP. All of them were heterozygous for FV-Leiden. One additional patient, who had partial correction of the APC-ratio, proved to be homozygous for the Leiden mutation. The remaining four samples, all of which had high positive tests for APAs, remained unchanged. One of these four was heterozygous for FV-Leiden, while the other three had normal FV. CONCLUSION: Normalisation of a low APC-ratio after dilution 1 + 1 with NP confirms the diagnosis of FV-Leiden. PCR analysis could be reserved for cases not affected by this procedure.

Antibodies, Antiphospholipid↗