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Biomedical subjects

J F Lassen

Publications and source records attributed to J F Lassen.

At least 19 recordsLinked to original sources

[Examination and treatment of dyslipemia after myocardial infarction--are the goals achieved?].

According to guidelines, medical treatment of dyslipidaemia in post-AMI patients should await assessment of underlying lipid disorders and the outcome of dietary treatment. The risk of patients not being treated with lipid-lowering therapy because of lack of follow-up has led to more aggressive guidelines recommending statin treatment even before discharge from hospital. In a study comprising 730 patients, we have shown that, although most patients were discharged from the coronary care unit without statin treatment, a traditional rehabilitation programme succeeded in assessing more than 95% of the patients for underlying lipid disorders, and more than 75% of patients with plasma cholesterol > or = 5.5 mmol/l received lipid-lowering therapy within the first year. Most patients were treated with statins. Statins, however, were given in smaller doses than those used in the clinical trials, and only 52% of the treated patients reached the recommended goal of plasma cholesterol lower than 5 mmol/l.

Adult↗

Electromechanical mapping for detection of myocardial viability in patients with ischemic cardiomyopathy.

BACKGROUND: We evaluated the ability of electromechanical mapping of the left ventricle to distinguish between nonviable and viable myocardium in patients with ischemic cardiomyopathy. METHODS AND RESULTS: Unipolar voltage amplitudes and local endocardial shortening were measured in 31 patients (mean+/-SD age, 62+/-8 years) with ischemic cardiomyopathy (ejection fraction, 30+/-9%). Dysfunctional regions, identified by 3D echocardiography, were characterized as nonviable when PET revealed matched reduction of perfusion and metabolism and as viable when perfusion was reduced or normal and metabolism was preserved. Mean unipolar voltage amplitudes and local shortening differed among normal, nonviable, and viable dysfunctional segments. Coefficient of variation for local shortening exceeded differences between groups and did not allow distinction between normal and dysfunctional myocardium. Optimum nominal discriminatory unipolar voltage amplitude between nonviable and viable dysfunctional myocardium was 6.5 mV, but we observed a great overlap between groups. Individual cutoff levels calculated as a percentage of electrical activity in normal segments were more accurate in the detection of viable dysfunctional myocardium than a general nominal cutoff level. The optimum normalized discriminatory value was 68%. Sensitivity and specificity were 78% for the normalized discriminatory value compared with 69% for the nominal value (P:<0.02). CONCLUSIONS: Endocardial ECG amplitudes in patients with ischemic cardiomyopathy display a wide scatter, complicating the establishment of exact nominal values that allow distinction between viable and nonviable areas. Individual normalization of unipolar voltage amplitudes improves diagnostic accuracy. Electroanatomic mapping may enable identification of myocardial viability.

Body Surface Potential Mapping↗

HbAlc in an unselected population of 4438 people with type 2 diabetes in a Danish county.

OBJECTIVE: To describe the use and level of HbA1c in a large unselected Type 2 diabetic population in Denmark. In addition, to describe the characteristics of the patients and the general practitioners in relation to the monitoring of HbA1c. DESIGN: Data were collected from public data files for the period January 1993 to December 1997. SETTING: The County of Vejle with a background population of 342,597 citizens, 303,250 of whom were listed with participating general practitioners. PATIENTS: The Type 2 diabetic population alive and resident in the county on 1 January 1997. RESULTS: In a population of 4438 Type 2 diabetics, 73% had a minimum of one annual HbA1c measurement in 1997. No HbA1c measurement was associated with a long history of diabetes, diet treatment or old age. Poor glycaemic regulation was found in 65% of the Type 2 diabetics in 1997. Poor glycaemic regulation was associated with tablet or insulin treatment, age under 70 years and long history of diabetes. The interpractice variation was huge. CONCLUSION: The quality of HbA1c monitoring of Type 2 diabetics needs to be improved. Possibilities for improvement seem to be present.

Aged↗

Intravenous magnesium does not influence the activity of the coagulation cascade.

Experimental arterial thrombus formation is reduced during intravenous magnesium infusion. It is well documented that magnesium reduces platelet reactivity, but the antithrombotic effect could also originate from anticoagulant properties or increased fibrinolysis. We therefore evaluated the effect of intravenous magnesium on prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin III complex (TAT) concentrations, and fibrin degradation products (FbDP) in a randomized, cross-over study in 14 healthy volunteers. Citrated blood samples were collected at 0, 30, and 180 min. An additional in vitro study on magnesium's effect on the activity of different coagulation factors was carried out. A transient increase was seen in F1 + 2 and TAT after 30 min but without any significant difference between the placebo and magnesium period. FbDP did not change significantly between the two treatments. Increasing concentrations of magnesium dose-dependently decreased binding of activated factor X to activated factor VII (FVIIa), but the decrease was slight and probably without any significance for coagulation at the concentrations tested. No effect was observed on the activity of FVIIa or activated factor VIII. In conclusion, no significant differences were observed on markers of coagulation or fibrinolytic activity during intravenous magnesium infusion. These results indicate that the observed antithrombotic effect of magnesium is more likely to arise from the previously observed platelet inhibition.

Adult↗

Use and validation of public data files for identification of the diabetic population in a Danish county.

INTRODUCTION: This study aims to describe the process of identifying people known to have diabetes through public data files, to validate this method, and to describe models for optimization of such identification processes. PATIENTS AND METHODS: In a study population of 303,250 citizens, the diabetics were identified by combining information from public data files with information from general practitioners. Data validity was checked by comparing the results of data searches in public data files against information from general practitioners and a random sample of diabetics. Two models were defined to optimize the use of public data files for identification of diabetics. In model A the minimum number of parameters needed to obtain a sensitivity as high as possible was identified. In model B the optimal combination of parameters needed to obtain a high positive predictive value combined with a high sensitivity was identified. RESULTS: A total of 5449 diabetics were identified. Of those 4438 (81%) were classified as Type 2 diabetics and 1011 (19%) were classified as Type 1 diabetics. The data validation revealed that one person was misclassified as a diabetic and 93 persons were misclassified as non-diabetics. In model A the identification parameters included: "prescription", "HbA1c", "chiropodist service" and "glucose service". In model B the optimal combination of parameters was identified as: minimum two HbA1c measurements, minimum one visit to a chiropodist, minimum one prescription or minimum one abnormal HbA1c during one year. CONCLUSION: Public data files are suitable for identification of both Type 1 and Type 2 diabetics. Models have been developed to identify diabetics and to promote the possibilities of long-term follow-up and quality assessment in an unselected diabetic population in a region.

Adult↗

Evaluation of a simple dosage scheme for transition from phenprocoumon to warfarin in oral anticoagulation.

Phenprocoumon, whose elimination half-time is 144 hours, has been the traditional oral anticoagulant of choice in Europe. However, today's most widely used drug is warfarin, whose elimination half-time is 40 hours. This study aims to evaluate a method for safe transition from phenprocoumon to warfarin, which is sometimes required. Hence, the large difference in their elimination rates may on occasion lead to serious overdosage upon transition from one drug to the other. According to average equipotent doses, a stepwise increase in warfarin dose was calculated based on the elimination half-times of the two drugs. The dosage scheme was subsequently tested in a pilot study including 35 patients. The conversion scheme was then adjusted based on the results from the pilot study. The new scheme was tested in 69 patients. The transition factor was 2.3, which implies that equipotency was achieved when the warfarin dose was 2.3 times larger than the phenprocoumon dose (in mg). This scheme proved optimal for 75% of the patients. However, the dose had to be adjusted individually in the remaining 25% of the patients to a level corresponding to the measured international normalised ratios. No patients experienced haemorrhages or thromboembolic complications during the period of changeover. In conclusion, the proposed scheme for changing medication from phenprocoumon to warfarin is safe and convenient.

Administration, Oral↗

[Anticoagulant treatment].

In 1998, the sale of vitamin K antagonists (VKA) in Denmark corresponded to the amount used for treatment of more than 20,000 patients for one year. This is more than three times more than ten years earlier. The reasons for the increasing use of VKA are new indications for permanent anticoagulant treatment, especially chronic atrial fibrillation and venous thromboembolism associated with permanent thromboembolic risk factors. The risk of bleeding is higher in the introductory phase of anticoagulant treatment than later on. It is now recommended to commence anticoagulant therapy without a loading dose. This seems to hasten a good estimate of the maintenance dose. The metabolism of VKA depends on a number of genetic and acquired factors. Knowledge of these factors is crucial for optimal regulation of the treatment, and it is important that patients at start of treatment are thoroughly informed about these factors in order to minimize the risk of complications.

Anticoagulants↗

Pathophysiology of coronary thrombosis.

Detailed knowledge of the pathophysiology as well as the dynamic nature of coronary thrombus formation provides a valuable tool for correct management and proper adjunctive therapy in patients with acute coronary syndromes. Coronary thrombosis is in the majority of cases caused by disruption or fissuring of an atherosclerotic plaque. At the lesion thrombogenic material will be exposed to the flowing blood leading to activation of platelets and the formation of a platelet clot. Simultaneously, the coagulation system is activated resulting in increased thrombin formation. Thrombin is a key mediator in arterial thrombosis, due to its effect on both platelets and fibrin generation. Thrombin contributes to the stabilization of an initially loose platelet clot by generating cross-bound fibrin within the thrombus. During the course of an acute coronary syndrome, the patient presents changing chest pain and dynamic ischaemic ECG findings. This is likely to be related to the dynamic nature of the pathophysiology. The presence of a non-occlusive coronary thrombus may deprive the myocardium its normal blood flow and oxygen supply, leading to ischaemic pain. During lysis or embolization, blood supply may be restored, but the presence of thrombus fragments in the microcirculation holds the potential to sustained interference with myocardial metabolism. The emboli contain activated platelets which release vasoconstrictors that may compromise the microcirculation. Recurrent thrombus formation at the lesion site may result in occlusion of the artery adding to the dynamic nature of the clinical presentation. In conclusion, platelets, the coagulation system, and the endothelium cause a dynamic process of intermittent occlusion, vasospasm and embolization of thrombus material.

Coronary Artery Disease↗

From science to everyday clinical practice. Need for systematic evaluation of research findings.

This paper focuses on problems attached to using scientific results in everyday clinical practice. Based on examples we raise the question: Are research results obtained under ideal scientific conditions, presented to health professionals and the public in a way that creates unrealistic expectations of the health services? We suggest that the clinical researcher, when reporting scientific results, should be obliged to consider technological aspects, i.e. the human and monetary cost, effectiveness, compliance, the expected consequence for the patient, professionals and society, and resources needed to accomplish it. Presented with these considerations, actors of the health care scene in terms of professionals, administrators, politicians and patients should be better suited to decide if implementation of a new treatment should take place. Such procedures will give the population and the politicians more realistic expectations of the contributions of medical science and the health services in general.

Adult↗

Near-patient test for C-reactive protein in general practice: assessment of clinical, organizational, and economic outcomes.

BACKGROUND: The benefits of near-patient, point-of-care tests have not been fully examined. We have assessed the clinical, organizational, and economic outcomes of implementing a near-patient test for C-reactive protein (CRP) in general practice. METHODS: In a randomized crossover trial during intervention periods, general practitioners (GPs) were allowed to measure CRP within 3 min, using NycoCard(R) CRP. During control periods, they had to mail blood samples for CRP measurements to the hospital laboratory and received test results 24-48 h later. Twenty-nine general practice clinics participated (64 GPs), and 1853 patients were included in the study. Results were evaluated at both the level of participating GPs and the level of included patients. RESULTS: For participating GPs, the overall use of erythrocyte sedimentation rates (ESRs) decreased by 8% (95% confidence interval, 1-14%) during intervention periods, and the number of blood samples mailed to the hospital laboratory decreased by 6% (1-10%). No reduction in the prescription of antibiotics was seen. The proportion of study patients having a follow-up telephone consultation was reduced from 63% to 53% (P = 0. 0001), and patients with CRP concentrations >50 mg/L had their antibiotic treatments started earlier when CRP was measured in general practices (P = 0.0161). CONCLUSION: The implementation of the near-patient CRP test was cost-effective mainly on the basis of a reduction in the use of services from the hospital laboratory by GPs. If the implementation is followed by education and clinical guidelines, opportunities exist for additional reduction in the use of ESR and for a more appropriate use of antibiotics.

Anti-Bacterial Agents↗

[Is the randomized controlled trial overvalued as a basis for clinical decision-making? A review with comments].

The randomized controlled trial (RCT) may have considerable limitations in clinical research. Lacking the possibility of blinding impairs the internal validity of the trials. The external validity is often impaired, as results of RCTs obtained in an ideal situation, may be difficult to generalize to a clinical routine situation. Pragmatic randomized trials move from ideal situations towards routine situations, and by modifying the design it is possible to reduce selection bias due to patient and physician preferences. Quasi-experimental studies have varying degrees of problems with internal validity but are necessary contributions to our knowledge of the effect of treatment in clinical routine situations. Limitations of the usefulness of RCTs as well as pragmatic and quasi-experimental studies in clinical research make it necessary to recognise that different methods complement one another. Research in development of RCTs and new methods in clinical research should be encouraged.

Decision Making↗

Effect of anticoagulant therapy on the hypercoagulable state in patients carrying the factor V Arg506Gln mutation.

Resistance to activated protein C, caused by a single point mutation in the factor V gene (Arg506Gln or FV Leiden), is the most prevalent single risk factor associated with venous thromboembolic disease. The aim of this study was to investigate the effectiveness of standard oral anticoagulant therapy (OAT) in patients with the Arg506Gln mutation compared with a matched control group. The study compared selected variables in 27 patients carrying the Arg506Gln mutation with 27 sex- and age-matched controls in steady state oral anticoagulant treatment (OAT). The study showed that similar doses of vitamin K antagonists in carriers and noncarriers suppress and generate a uniform distribution of coagulation markers in steady state OAT. Thus, it seems that OAT with standard treatment doses is just as effective in patients with the Arg506Gln mutation as in comparable controls without the mutation.

Activated Protein C Resistance↗

[Cross-sectional therapeutic programs--an example of a cooperative health care system. A review with comments].

There is no tradition for sharing the responsibility for episodes of care between the primary and secondary sectors in the Danish health care system. Concurrently with increased international experience with shared care programmes, there is also a growing interest in Denmark in cooperation between the sectors. Based on literature research, shared care programmes are presented as a method of ensuring continuity and quality in treatment of chronic diseases. Experiences in the areas of diabetes, asthma, rheumatoid arthritis, and cancer are described. It is concluded that the Danish health care system is well prepared for the implementation of shared care programmes; there are only few sources of payment in the system, and an extensive continuing medical education system ensures that general practitioners can participate in relevant education. The implementation of shared care programmes in Denmark should be followed by scientific evaluation and documentation of the quality of the treatment programmes.

Delivery of Health Care↗

[Diagnostic value of C-reactive protein in bacterial infections. Review of the literature].

Conflicting data for predictive values for C-reactive protein (CRP) in its ability to distinguish between viral and bacterial diseases are reviewed. Study designs regarding setting, patient-mix, severity of disease and prevalence seem to determine the magnitude of predictive values. We have calculated predictive values for patients suspected of septicaemia, meningitis, appendicitis, cholecystitis, upper- and lower respiratory disease, acute sinusitis and acute otitis media, and revealed the highest predictive values among patients suspected for severe and generalized infections. More localized diseases have lower predictive values. We emphasize the importance of a study design where the circumstances resemble the real situations in which the test is supposed to be used. This will ensure the clinical applicability of predictive values for a diagnostic test.

Adult↗

[Differences in the use of C-reactive protein analysis and erythrocyte sedimentation in general practice and hospitals. Development from 1986 to 1995].

Analysis for C-reactive protein (CRP) was introduced in the Vejle Hospital catchment area in 1987. During the next ten year period the use of CRP has increased to reach a stable level both on hospital wards, out-patient clinics and in general practice. While the use of erythrocyte sedimentation rate on wards has decreased correspondingly, this is not seen in out-patient clinics or in general practice. There are medical as well as practical reasons for this discrepancy. It is believed that the possibility of performing a CRP as a point-of-care test in the GPs office in the future will lead to a reduction in the number of analyses of erythrocyte sedimentation rate performed in general practice as well.

Blood Sedimentation↗

The Arg506Gln mutation (FV Leiden) among a cohort of 4188 unselected Danish newborns.

Resistance to activated protein C (APC) is the most prevalent single phenomenon associated with thromboembolic disease. It is caused by a single point mutation in the factor V gene (Arg506Gln or FV Leiden), replacing an Arg506 with a Gln at the APC-cleavage site in factor V. In this study we present a prevalence study of the Arg506Gln mutation in a large Danish cohort. By screening 4188 newborns (8376 alleles) we identified 3.4% alleles (95% CI: 3.0-3.8) of the Arg506Gln mutation, corresponding to a heterozygous prevalence of 6.6% (95% CI: 5.9-7.4) in Denmark. This is significantly lower than what has been reported from southern Sweden. The birth cohort has been selected from the entire country, providing representative and accurate estimates of the gene frequencies. Equal gender distribution was found, and the Arg506Gln mutation is probably not a considerable risk factor in fetal life in the general population.

Cohort Studies↗

Markers of coagulation and fibrinolysis as measures of disease activity in inflammatory bowel disease.

BACKGROUND: Activation of coagulation and fibrinolysis occurs in patients with inflammatory bowel disease. Our aim was to study the course of a marker for activation of the coagulation cascade, prothrombin fragment 1 + 2 (F1+2), and fibrinolysis, fibrin degradation products (FbDP), in patients with ulcerative colitis and Crohn's disease before and during therapy with glucocorticoids. METHODS: Twenty-seven patients with active ulcerative colitis and 42 with active Crohn's disease treated with glucocorticoids were studied. Plasma samples were drawn before, during, and at end of therapy or at time of treatment failure. F1+2 and FbDP were measured with commercially available enzyme immunoassays. RESULTS: Mean base-line concentrations of F1+2 were significantly increased in patients with ulcerative colitis (4.77 +/- 0.50 nmol/l; P < 0.0001) and in Crohn's disease (4.66 +/- 0.59 nmol/l; P < 0.0001) compared with healthy controls (1.57 +/- 0.09 nmol/l). Mean base-line concentrations of FbDP were significantly increased in patients with ulcerative colitis (1264 +/- 161 microg FE/l; P < 0.0001) and in Crohn's disease (491 +/- 51 microg FE/l; P < 0.0001) compared with healthy controls (194 +/- 21 microg FE/l). During treatment with glucocorticoids the plasma concentrations of FbDP decreased in patients with Crohn's disease achieving remission and in patients with ulcerative colitis avoiding surgery but remained unchanged in patients not responding to therapy. In contrast, F1+2 remained increased in patients with Crohn's disease and ulcerative colitis irrespective of outcome. CONCLUSION: The present data support the concept that coagulation cascade and fibrinolysis is activated in patients with active inflammatory bowel disease. F1+2 and FbDP correlate poorly with the clinical disease activity and acute-phase reactants. The clinical response to treatment with glucocorticoids is accompanied by a decrease in plasma concentrations of FbDP but not in F1+2. FbDP may emerge as a new marker in the assessment of disease activity in patients with inflammatory bowel disease.

Adult↗