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Biomedical subjects

I Brandslund

Publications and source records attributed to I Brandslund.

At least 37 records · Page 2Linked to original sources

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↗

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↗

[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↗

Streptokinase, complement activation and hypotension.

The purpose of this study was to establish whether complement activation is the cause of transient hypotension during streptokinase infusion in patients with acute myocardial infarction. Thirteen patients with suspected acute myocardial infarction and treated with streptokinase were included. Complement 3d (C3d) as an indicator of complement activation was assessed in venous blood and blood pressure was measured. Ten patients had verified myocardial infarction. Three patients did not. Five patients developed an increase in C3d blood levels of more than 200% within 30 min. All patients developed a transient fall in blood pressure during infusion of streptokinase. This was related neither to presence of myocardial infarction nor to degree of complement activation. The mechanism of hypotension observed following the administration of streptokinase is not through complement activation, and thus how streptokinase induces hypotension is still obscure.

Acute Disease↗

C-reactive protein in general practice--how commonly is it used and why?

OBJECTIVE: C-reactive protein (CRP) is a well-known diagnostic tool in general practice. The scope of this study was to assess how frequently CRP is used by general practitioners and to evaluate the reasons for using it. DESIGN: A retrospective part based on data from a laboratory database system, and a prospective part with a questionnaire-based registration. SETTING: 30 general practice clinics in the catchment area of Vejle County Central Hospital. SUBJECTS: Retrospectively, all patients from general practice serviced by the laboratory for one year. Prospectively, 1190 patients from whom a blood sample was taken for CRP-measurement during a 2 month study period. MAIN OUTCOME MEASURES: The frequency of using CRP and the reason requesting it; A) diagnosing a new disease, B) monitoring a well-known disease, or C) "screening". Furthermore; 1) infections, 2) chronic inflammatory disease, 3) malignant disease, or 4) others. RESULTS: CRP-measurements were ordered in 3.7% of all consultations in general practice and for 34.1% of all patients whose blood sample was analysed at the central laboratory. The use of CRP was as follows: A-1: 28.6%, A-2: 6.7%, A-3,4: 9.3%, B-1: 8.2%, B-2: 12.4%, B-3,4: 6.5%, C-1: 5.7%, C-2: 3.2%, C-3: 3.5% and C-4: 15.2%. Diagnosing a new (infectious) disease was the most frequent single reason for CRP-measurement. There was major interpractice variation. CONCLUSIONS: CRP is frequently used in general practice, mostly (65.4%) in the field of infections and chronic inflammatory diseases. Because of major interpractice variation, the most correct way of using CRP should be evaluated and guidelines should be provided.

Adolescent↗

Quality assessment of blood glucose testing in general practitioners' offices improves quality.

Measurement of blood glucose is a frequent test in Danish physicians' offices. We describe here a new design of external quality assessment wherein fresh, unstabilized whole-blood samples were analyzed by the physicians' office methods and by a hospital laboratory comparison method (glucose dehydrogenase assay, calibrated against NIST 909a). This approach was used in the offices of 171 general practitioners in our county during a 5-year period. The first survey, in 1992, revealed unsatisfactory performance in terms of our criterion that no difference between the physician's office and the hospital laboratory's single result should exceed +/-20% of the laboratory result. After initiation of a program of consultation and assistance, the proficiency testing rounds of 1994 and 1996 showed considerable improvement. Thus, whereas in 1992 12% of the values were outside the acceptance limits, in 1994 and 1996 the respective values were 4% and 3%. We believe the effect was mainly related to improvements in choice of technology, procedures, and handling of specimens. We conclude that the use of bedside instruments should be restricted to diagnosis of only severe hypo- or hyperglycemia and to monitoring glucose >5 mmo/L in already diagnosed diabetics. Our program differs from previous approaches to quality assessment and could also be useful for large hospitals' in-house proficiency testing.

Blood Glucose↗

Evaluation of a near-patient test for C-reactive protein used in daily routine in primary healthcare by use of difference plots.

We have assessed the technical performance and robustness of NycoCard CRP Whole Blood, a near-patient test for C-reactive protein (CRP), when used in realistic daily routine situations in general practice clinics (GPC). Thirteen GPCs participated, five of them with technician staff. From 898 patients, split-sample measurements for CRP were made. Results from GPCs were compared with results from a turbidimetric laboratory method, traceable to international reference preparations (IFCC CRM 470). Results were evaluated in difference plots where the expected distribution, due to an estimated analytical variation, was compared with measured differences. Of all difference points, 91.5% (n = 819) were within a 95% prediction interval based on the imprecision of both methods. Mean bias (95% confidence interval) was -0.3 mg/L (-0.9 to 0.3). No differences in analytic quality were found between GPCs with technician staffs and GPCs without, and between test results obtained within the first and second week, compared with the rest of the study period. We find the test as good when used in GPCs as could be expected from laboratory testing, and consequently robust, which is a necessity for use in routine situations in general practice. General application of difference plots in test evaluations are discussed in detail.

Adolescent↗

Biological variation of International Normalized Ratio for prothrombin times, and consequences in monitoring oral anticoagulant therapy: computer simulation of serial measurements with goal-setting for analytical quality.

Oral anticoagulant therapy (OAT) has a well-established efficacy in prophylaxis and treatment of thromboembolic disorders. Because complications are related to intensity of OAT, optimal control of treatment is mandatory. In studies of OAT, as many as 30% of International Normalized Ratio (INR) measurements for prothrombin times fall outside the therapeutic interval. Preanalytical, analytical, and biological variation all contribute to this. Computer simulations of serial INR measurements were performed for various assumed in-treatment setpoints within the therapeutic interval INR 2.0-3.0 and for an "in-treatment within-subject variation" (CV) of 10.1%. Results are presented in difference plots with therapeutic intervals and critical differences. If the in-treatment setpoint is mid-interval (INR = 2.5), only 5% of simulated INR values fall outside the therapeutic interval. Setpoints deviating from the mid-interval and increases in the in-treatment within-subject variation considerably increase the number of observations outside the therapeutic interval and the critical differences. In conclusion, random variation, biological or analytical, and setpoints (targets) deviating from mid-interval explain a substantial number of the INR values outside therapeutic intervals observed in clinical studies. Analytical imprecision should be kept < 5% and analytical bias < +/- 0.2 INR.

Administration, Oral↗

[Resistance to activated protein C. The most common cause of familial thrombophilia].

Resistance to activated protein C (APC) is caused by the most prevalent single gene defect associated with thromboembolic disease so far described. The majority of cases are caused by a single point mutation in the Factor V gene, which predicts replacement of Arg506 in the APC-cleavage site with a Gln. APC resistance is found in 20-60% of patients with venous thrombosis and in 3-10% of the normal population among Caucasians. In its heterozygous state, the mutation is associated with a 5-10-fold increased risk of thrombosis. Homozygosity is associated with more severe APC resistance, and a higher risk of developing thrombosis. By the age of 33 years, 8% of normals, 20% of heterozygotes, and 40% of homozygotes have had manifestations of venous thrombosis. APC resistance has been described in 60% of women with thromboembolic complications during pregnancy and in approximately 30% of women with thromboembolic complications using oral contraceptives. Development of clinical episodes of thrombosis in patients with APC resistance is likely to occur on a multifactorial basis. Hypercoagulable states may result from multigene interactions, and prothrombotic insults in patients with an inherited predisposition may precipitate thrombotic complications. In this review we present and discuss results from the recent medical literature.

Anticoagulants↗

Interpretation of serial measurements of international normalized ratio for prothrombin times in monitoring oral anticoagulant therapy.

Despite careful monitoring of oral anticoagulant treatment (OAT), some international normalized ratio (INR) for prothrombin time values will fall outside the therapeutic range. Considerable changes in serial INR results from OAT patients may be caused by random fluctuation alone, and, for statistical reasons, a fraction of the INR values will fall outside therapeutic range and interfere with dose adjustments. On the basis of therapeutic intervals and statistical evaluation of reference changes, we suggest and discuss an alternative method for interpretation of serial INR measurements. Retrospective evaluation of serial measurements of INR from OAT patients revealed an "overshooting" phenomenon. When a dose was adjusted on the basis of insignificant change in INR value, the subsequent INR value generally fell in the opposite direction. If a further change of dose was initiated because of the new INR value, a similar course in the opposite direction was observed. This "ping-pong" effect renders patients in a fluctuating state of anticoagulation and may introduce increased risk of complications. The suggested method provides an objective criterion for dose adjustments in OAT, which should reduce patients' risk.

Anticoagulants↗

International normalized ratio for prothrombin times in patients taking oral anticoagulants: critical difference and probability of significant change in consecutive measurements.

To determine when a change in serial measurements of prothrombin time in patients receiving oral anticoagulant therapy (ACT) is a statistically significant biological change necessitating dose adjustment, one must know the size of the "critical difference" in statistical terms (i.e., probabilities). In a cohort of 32 ACT patients at pharmacological steady-state, we studied the within-subject total variation of prothrombin time, expressed as International Normalized Ratio (INR), over 6 months. The total within-subject variation (CV) of INR was 10.1%. The corresponding critical differences required for significance of change in serial INR results was 0.7 at a therapeutic target of 2.5 INR and 1.0 at a therapeutic target of 3.5 INR. The data presented allow generation of objective criteria for monitoring ACT patients and deciding dose adjustments. We recommend that estimations of critical differences for significant change of INR in ACT patients should be based on results obtained in the specific clinic investigated to mirror the routine total variation of INR measurements they obtain.

Aged↗

Low normal alpha-1-antitrypsin serum concentrations and MZ-phenotype are associated with byssinosis and familial allergy in cotton mill workers.

Recent studies have shown a close association between byssinosis and airborne endotoxin concentrations. Endotoxin might induce byssinosis through the release of biochemical mediators as the broncheoalveolar surface. Alpha-1-antitrypsin (alpha-1-A) which neutralizes enzymes released by granulocytes is known to be important. This study evaluates the possible importance of alpha-1-A concentration and the heterozygosity (Pi-S and Pi-Z alleles), in the prevalence of byssinosis and familial allergy. 253 cotton workers were interviewed and clinically studied to identify persons with the cotton lung disease, byssinosis, and atopic disease. Serum was available for alpha-1-A concentration determination in 226 individuals, and for Pi phenotyping in 206. The overall prevalence of byssinosis was 30/226 (13%). In the group with alpha-1-A < or = 35 mumol l-1 the prevalence was 5/18 (28%), versus the prevalence 25/208 (12%) in the group with alpha-1-A > 35 mumol l-1 (p < 0.1, Fishers exact test). MZ phenotype was associated with an increased prevalence of byssinosis compared with the MM-group: 3/8 (38%) and 25/187 (13%), p < 0.1, Fishers exact test. An association between MZ-phenotype and familial allergy was found: 4/8 (50%) contra 23/187 (12%), p < 0.05, Fishers exact test. In a logistic regression model controlling for confounding by endotoxin, tobacco exposure, sex, and age, the odds ratio for byssinosis in the MZ-phenotype group was significantly elevated 5.8 (1.1-30.3). Odds ratio for familial allergy was also significantly elevated in the MZ-group 2.8 (1.3-5.9).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗