Comparison of two- and three-dimensional transthoracic echocardiography to cardiac magnetic resonance imaging for assessment of paravalvular regurgitation after transcatheter aortic valve implantation.

This study evaluated 2-dimensional (2D) transthoracic echocardiography (TTE) using Valve Academic Research Consortium-2 (VARC-2) criteria and 3-dimensional (3D) TTE for assessment of aortic regurgitation (AR) after transcatheter aortic valve implantation (TAVI) in comparison with cardiac magnetic resonance (CMR) imaging. In 71 patients, 2D TTE, 3D TTE, and CMR imaging were performed to assess AR severity after TAVI. Using 2D TTE, AR severity was graded according to VARC-2 criteria and regurgitant volume (RVol) was determined. Three-dimensional color Doppler TTE allowed direct planimetry of the vena contracta area of the paravalvular regurgitation jet and calculation of the RVol as product with the velocity-time integral. RVol by CMR imaging was measured by phase-contrast velocity mapping in the ascending aorta. After TAVI, mean RVol determined by CMR imaging was 9.2 ± 9.6 ml/beat and mean regurgitant fraction was 13.3 ± 10.3%. AR was assessed as none or mild in 58 patients (82%) by CMR imaging. Correlation of 3D TTE and CMR imaging on RVol was better than correlation of 2D TTE and CMR imaging (r = 0.895 vs 0.558, p <0.001). There was good agreement between RVol by CMR imaging and by 3D TTE (mean bias = 2.4 ml/beat). Kappa on grading of AR severity was 0.357 between VARC-2 and CMR imaging versus 0.446 between 3D TTE and CMR imaging. Intraobserver variability for analysis of RVol of AR after TAVI was 73.5 ± 52.2% by 2D TTE, 16.7 ± 21.9% by 3D TTE, and 2.2 ± 2.0% by CMR imaging. In conclusion, 2D TTE considering VARC-2 criteria has limitations in the grading of AR severity after TAVI when CMR imaging is used for comparison. Three-dimensional TTE allows quantification of AR with greater accuracy than 2D TTE. Observer variability on RVol after TAVI is considerable using 2D TTE, significantly less using 3D TTE, and very low using CMR imaging.

Development and validation of a risk-score model for subjects with impaired glucose tolerance for the assessment of the risk of type 2 diabetes mellitus-The STOP-NIDDM risk-score.

AIMS: To develop a risk-score model, based on available clinical data to assess absolute risk of type 2 diabetes among people with impaired glucose tolerance (IGT). METHODS: Data from the study to prevent non-insulin dependent diabetes mellitus (STOP-NIDDM) investigating acarbose treatment in individuals with IGT were used to develop multivariable Cox proportional hazards model for the time to onset of diabetes. The final model equation was externally validated using data from the Finnish Cardiovascular Risk Factor (FINRISK) population. RESULTS: The risk-score model included the variables acarbose treatment, gender, serum triglyceride level, waist circumference, fasting plasma glucose, height, history of cardiovascular disease (CVD) and hypertension. The final model yielded an area under the receiver-operating-characteristic curve (AUC(ROC)) of 0.64 when applied to people with IGT in the STOP-NIDDM, and 0.84 and 0.90 when applied to FINRISK population with IGT alone and IGT and normal glucose tolerance combined, respectively; AUC(ROC) is a measure of the discriminatory power of the model (1, perfect discrimination). CONCLUSIONS: The STOP-NIDDM risk-score is a simple and validated tool that can identify high-risk individuals with IGT who would benefit most from type 2 diabetes or CVD prevention strategies, such as lifestyle management or early acarbose treatment.

Assessment of the antiobstructive effect of fexofenadine on nasal allergy challenge in patients with seasonal allergic rhinitis.

The oral administration of fexofenadine 120 mg daily is a common treatment of seasonal allergic rhinitis (SAR). It reduces the H1 receptor-mediated symptoms, such as sneezing, pruritus, and nasal secretion as well as non-nasal symptoms such as conjunctivitis. The objective was to assess the effect of fexofenadine on nasal symptoms (such as nasal obstruction) in seasonal allergic rhinitis. A placebo-controlled, double-blind, randomized, cross-over study was performed which yielded evidence that two-week therapy with fexofenadine 120 mg daily in patients with SAR also relieves nasal obstruction and congestion. The parameters of nasal obstruction were evaluated by means of rhinoscopy, a subjective symptom score, and active anterior rhinomanometry. The subjective evaluation of nasal obstruction/congestion as recorded by the patient every 15 minutes for 4.5 hours after nasal allergen provocation showed a significant difference of the AUC (p = 0.025) between fexofenadine and placebo with a 12.8% lower obstruction after fexofenadine. The swelling of the nasal mucosa, which was assessed by rhinoscopy for 4.5 hours after nasal allergen provocation, was 21% lower after treatment with fexofenadine (p = 0.041). In this double-blind, placebo-controlled trial, subjective patient ratings as well as objective investigator assessments demonstrate the anti-obstructive effect of fexofenadine in nasal allergen challenge.

[Comparative evaluation of sponsored and unsponsored continuing medical education]. / Evaluation der Fortbildung: Einfluss des Sponsorings im Urteil der Teilnehmer.

BACKGROUND AND PURPOSE: Continuing medical education (CME), by law, has to be free of commercial influences. Sponsoring of CME in Germany has never been evaluated regarding potential influences on presentation of data and perception of participants. The present paper evaluates the impact of sponsoring on accredited CME events. MATERIAL AND METHODS: All CME events accredited by the Chamber of Physicians North Rhine have to be evaluated by a standard evaluation form. The data of 23,240 physicians participating in 1,019 consecutive CME events (representing 13.5% of all accredited events in the sampling period from February 2002 to May 2003) have been analyzed. RESULTS: Nearly two thirds of all participants were specialists. 64.6% of all evaluation forms had been sent back from sponsored CME events. Participants in sponsored events were older and, regarding the topic of the presentation, they were more often familiar with and had a diagnostic and therapeutic strategy for the clinical problem presented. Both types of CME events were rated good to excellent regarding a set of evaluation categories, about 28% of all participants felt their personal strategy had been changed by the event. On 7.7% of all evaluation forms (10% in sponsored and 3.4% in sponsored events; p<0.001), the participants noted a commercial bias. The participants who noted a commercial bias were more experienced in the topic discussed, found the presentation of data more often incomplete, and felt a negative impact on their learning behavior. CONCLUSION: Sponsored and unsponsored CME events are rated as equally satisfactory by the great majority of participants. Only in about 8% of the evaluation forms a commercial bias was noted, which had a negative impact on the educational value of the CME event. Thus, it seems most likely that the regulatory framework for accreditation is able to prevent large-scale commercial influence on CME events.

Economic evaluation of enoxaparin for anticoagulation in early cardioversion of persisting nonvalvular atrial fibrillation: a statutory health insurance perspective from Germany.

OBJECTIVE: To estimate, from the perspective of Statutory Health Insurance (SHI, third-party payer) in Germany, the economic consequences of using the subcutaneous low-molecular-weight heparin (LMWH) enoxaparin instead of intravenous unfractionated heparin followed by oral phenprocoumon (UFH/PPC) for anticoagulation in patients undergoing transesophageal echocardiography (TEE)-guided early electrical cardioversion (ECV) of persisting nonvalvular atrial fibrillation (AF) without intracardiac clot. DESIGN AND SETTING: The incremental cost for the enoxaparin-based regimen versus the UFH/PPC-based regimen was chosen as the target variable. A decision-analytic model considering the in- and outpatient sectors was used to quantify the target variable. Resource use during in- and outpatient treatment was taken from the Anticoagulation in Cardioversion using Enoxaparin (ACE) trial and from expert interviews with cardiologists in Germany in order to reflect the day-to-day conditions of clinical practice. Costs were given by SHI expenses for inpatient treatment and for medical services, drugs, disposables, and laboratory tests during outpatient treatment. These costs were determined by multiplying utilized resource items by the price or tariff of each item based on German healthcare regulations for the reference period of 2003/2004. According to the ACE trial, the evaluation encompassed 28 (26-30) treatment days with two consecutive phases. Phase I with 5 (3-12) days comprised diagnostics, start of anticoagulation, and ECV. Phase II with the remaining days consisted of continued anticoagulation and patient monitoring. The dosage of enoxaparin was 1 mg/kg bodyweight twice daily in treatment phase I followed by 40 mg twice daily with a bodyweight <65 kg or 60 mg twice daily with a BW > or =65 kg in treatment phase II. The daily dosages of UFH by continuous infusion and overlapping PPC were adjusted to an International Normalized Ratio of 2.0-3.0 in treatment phase I followed by 2.25mg PPC once daily in treatment phase II. Patients with any comorbidity and complication level (CCL) and those with low comorbidity and complications expected to occur in rare cases only (low-risk patients) were analyzed separately. In each base-case analysis, exclusively point estimates of all respective model parameters were applied. MAIN OUTCOME MEASURES AND RESULTS: There were savings of 339 euro and 579 euro per patient receiving the enoxaparin-based regimen versus the UFH/PPC-based regimen in the case of patients with any CCL and of low-risk patients, respectively (1 euro approximate, equals $US1.25; first quarter 2004 values). In comprehensive sensitivity analyzes, the robustness of the model and its results was shown. First, the impact of the model parameters on the target variable for each patient group was quantified in a deterministic model. Secondly, the dependency of the target variable on random variables was described for each patient group using Monte Carlo simulation. Irrespective of the patient group, the cost weight and the base rate of hospitals for inpatient ECV in phase I turned out to have the greatest impact on the savings obtained by the enoxaparin-based regimen. In the case of patients with any CCL, this impact was about 1.4-fold of that of the probability of enoxaparin patients undergoing outpatient ECV in phase I. In the case of low-risk patients, the impact of the cost weight and the base rate of hospitals for inpatient ECV in phase I was about 4.1-fold of that of the price of enoxaparin 60 mg prefilled syringes in the outpatient sector. In 79% and 93% of 10,000 simulated comparisons each versus the UFH/PPC-based regimen, there were savings obtained by the enoxaparin-based regimen in patients with any CCL and in low-risk patients, respectively. CONCLUSIONS: Results of this evaluation showed that an enoxaparin-based regimen for TEE-guided ECV of AF in patients without intracardiac clot offers SHI in Germany a considerable saving potential when used instead of an UFH/PPC-based regimen.

Comparison of the biological activity of the most common sublingual allergen solutions made by two European manufacturers.

BACKGROUND: The clinical efficacy of sublingual immunotherapy has been documented in numerous studies and meta-analyses and is argued to be a favored alternative to the subcutaneous route if allergic symptoms are treated with a high-dose therapy. What is still lacking is a 'conversion rate' between the biological activities of different allergen solutions to determine the one with the higher concentration. METHODS: A randomized, double-blind, parallel-group study was done with three groups sensitized to the allergens birch, grass or house dust mite via skin prick test. Staloral in the concentrations 10, 100 and 300 IR and SLITone in the concentration of 1,000 STU per milliliter were used for a computer-based comparison of the geometric mean wheal sizes of the different solutions. For each patient, individual regression curves led to the calculation of a mean corresponding IR value for the SLITone solution. RESULTS: A total of 47 patients took part in this clinical trial, most of whom were sensitized to more than one allergen. Values for birch (30 patients) showed that 1,000 STU corresponded to 77 IR, for grass (29 patients) 1,000 STU matched 78 IR and for house dust mite (30 patients) 1,000 STU matched 27 IR based on dose-response relationships. The Wilcoxon test showed that for all allergens the allergenic activity of the SLITone solution was significantly higher than the 10 IR solution and significantly lower than the 100- and 300-IR solutions. CONCLUSION: We established a conversion rate between the two leading sublingual allergen solutions on the European market to compare different units of measurement.