Incidence and clinical presentation of acute otitis media in children aged <6 years in European medical practices.

We conducted an epidemiological, observational cohort study to determine the incidence and complications of acute otitis media (AOM) in children aged <6 years. Data on physician-diagnosed AOM were collected from retrospective review of medical charts for the year preceding enrolment and then prospectively in the year following enrolment. The study included 5776 children in Germany, Italy, Spain, Sweden, and the UK. AOM incidence was 256/1000 person-years [95% confidence interval (CI) 243-270] in the prospective study period. Incidence was lowest in Italy (195, 95% CI 171-222) and highest in Spain (328, 95% CI 296-363). Complications were documented in <1% of episodes. Spontaneous tympanic membrane perforation was documented in 7% of episodes. Both retrospective and prospective study results were similar and show the high incidence during childhood in these five European countries. Differences by country may reflect true differences and differences in social structure and diagnostic procedures.

[Mechanics and effects of European reference pricing for vaccines in Germany according to §130a Abs. 2 SGB V: an analysis using the example of influenza vaccines]. / Funktionsweise und Auswirkungen des Referenzpreissystems bei Impfstoffen nach §130a Abs. 2 SGB V: eine Analyse am Beispiel der Grippeimpfstoffe.

OBJECTIVES: On 01 January 2011 the bill for the reorganisation of the pharmaceutical market became effective. Since that time there is a European reference pricing (ERP) system for vaccines in order to bring down the German vaccine prices to an assumed lower European level. This study describes the implementation, functioning and effect of this new system. For influenza vaccines the impact of ERP on the price level and spread of prices is analysed. METHODS: The description of the mechanism is based on the law and corresponding regulations of the head association of sickness funds (GKV-SV). The analysis of vaccine prices is based on the data of the i:data report (status of 01 September 2011) of ifap Service Institute. RESULTS: The European reference price is calculated as the average price of the manufacturer-selling-prices of the corresponding vaccine in the 4 countries of the European Union whose gross national income comes closest to the German one and in which the vaccine is distributed. The relied prices are weighted by sales and purchasing power parities of the respective countries. This analysis suggests that in particular the practical implementation of the reference price system should be further improved and specified. The calculation of the reference prices should ensure price comparability. In addition, significant problems remain in the deduction of discounts, because no distinction is made in the documentation of vaccinating doctors, whether vaccination was performed as a compulsory or statutory benefit. The comparison of the manufacturer-selling-prices of individual influenza vaccines with the corresponding reference prices shows an enlargement of the existing price differences, which have evolved in a competitive environment, after the implementation of the reference pricing -system. CONCLUSIONS: There is still a need for improvement in implementing the reference pricing system. In the most competitive vaccine market of influenza vaccines, the ERP-system lowers the prices, but seems to distort the market prices.

Pretransplant coronary artery disease is a predictor for myocardial infarction and cardiac death after liver transplantation.

BACKGROUND: Cardiovascular disease is a serious problem of liver transplant (LT) recipients because of increased cardiovascular risk due to immunosuppressive therapy, higher age, intraoperative risk and comorbidities (such as diabetes and nicotine abuse). Reported frequency of cardiovascular events after LT shows a high variability between different LT cohorts. Our aim was to analyze a cohort of LT recipients from a single center in Germany to evaluate frequency of the cardiovascular endpoints (CVE) myocardial infarction and/or cardiac death after LT and to investigate correlations of CVE post LT with pretransplant patient characteristics. PATIENTS: In total, data from 352 LT patients were analyzed. Patients were identified from an administrative transplant database, and all data were retrieved from patients' charts and reports. RESULTS: During the median follow-up of 4.0 (0-13) years, 10 cases of CVE were documented (six myocardial infarctions and four coronary deaths). The frequency of CVE did not differ according to classic cardiovascular risk factors such as body mass index (p=0.071), total cholesterol (p=0.533), hypertension (p=0.747), smoking (p=1.000) and pretransplant diabetes mellitus (p=0.146). In patients with pretransplant coronary heart disease (n=24; 6.8%) CVE were found more frequently (p=0.024). CONCLUSION: In summary, we found a rate of 2.8% CVE after LT in a German transplant cohort. Pretransplant CHD was the only risk factor for CVE, but showed no significant impact on overall survival.

Differentiation between malignant and benign solitary pulmonary nodules with proton density weighted and ECG-gated magnetic resonance imaging.

OBJECTIVE: To estimate performance of MRI for differentiating malignant from benign solitary pulmonary nodules (SPN) using morphological characteristics. MATERIAL AND METHODS: MRI in 46 patients with SPN (mean diameter: 19 mm) was carried out on 1.0 Tesla scanner using ECG-gated, gradient echo sequence. Morphological signs of SPN were determined and compared with previously performed helical-CT, where final diagnosis served as reference with 52% frequency of malignancy. Furthermore, three observers evaluated all images. RESULTS: Significant differences between the two groups were found for nodules shape, margin, inhomogeneity and the vessel-sign in MRI, nodules shape, margin, the vessel-sign, and presence of spicules in CT. Using these signs, AUC were 0.746 for MRI and 0.765 for CT. The mean sensitivity, specificity, and accuracy of observers for MRI/CT were 89%/95%, 42%/41%, 66%/68%, respectively. CONCLUSIONS: Despite discrepancies in morphologic appearance, no significant difference of accuracy between MRI and CT was determined. Further investigations are necessary to demonstrate the clinical use in combination with functional parameters, establishing MRI as a comprehensive diagnostic modality for SPN.

[Detection of pulmonary nodules with breath-hold magnetic resonance imaging in comparison with computed tomography]. / Detektion von Lungenrundherden mit der Magnetresonanztomographie in Atemanhaltetechnik im Vergleich zur Spiral-Computertomographie.

PURPOSE: Evaluation of sensitivity and false positive findings of two fast MRI sequences for the detection of pulmonary nodules in comparison with spiral CT by two independent observers. MATERIALS AND METHODS: All 30 enrolled patients had a spiral CT or MSCT as base line study. MRI was performed with a 1.5 T MR scanner (Sonata, Siemens) using a transverse 3D gradient echo sequence (3D-GRE: TR/TE/flip = 2.9 ms/1.1 ms/5 degrees ) and a half-Fourier single-shot fast spin-echo sequence (HASTE: TR/TE/flip = 800/25/150 degrees ) acquired in three planes. A separate analysis for both sequences was carried out prospectively by two independent readers (A and B) with different experience regarding pulmonary MRI. Additionally, a retrospective reading with knowledge of the CT scans was done. Results were calculated for all lesions and for lesions larger than 4 mm. RESULTS: The sensitivities were 73 %, 70 % and 84 % for the 3D-GRE sequence (reader A, reader B, retrospective reading) and 65 %, 68 % and 81 % for the HASTE sequence. For lesions larger than 4 mm, the sensitivities were 93 %, 89 %, 96 % for the 3D-GRE sequence and 85 %, 85 %, 96 % for the HASTE sequence. The rate of false positive findings depended on the reader's experience, but was generally lower for the 3D-GRE sequence with 2 and 16 (reader A and B) false positive nodules compared to 4 and 40 false positive findings for the HASTE sequence. The 3D-GRE sequence was more accurate for both readers (reader A: p = 0.08, reader B: p = 0.00003). CONCLUSION: The sensitivity of MRI for the detection of lung nodules was only acceptable for lesions larger than 4 mm. The 3D-GRE sequence is superior to the HASTE sequence due to the reduced amount of false positive findings with comparable sensitivity.

Guar and its effects on metabolic control in type II diabetic subjects.

The effect of guar mini-tablets (5 g t.i.d.) on carbohydrate and lipid metabolism of outpatients with overt diabetes mellitus with glycosuria (is greater than 5 g/24 h) was determined in an open-controlled, randomized, multicenter, crossover study. A 4-wk pretreatment period was followed by a 6-wk treatment period. The treatment period consisted of a 2-wk guar period (treatment period II), which was followed by the wash-out period. The other half of the patients received treatment in the reverse order. Out of 93 patient records, 79 (41 sulfonylurea [SU] and 38 insulin-treated) were suitable for statistical analysis. No relevant weight-reducing effect of guar could be found in both 2-wk treatment periods. At the end of treatment period II, the lowering of the 1-h postprandial values of blood glucose (SU 12%, insulin 10%), cholesterol (SU and insulin 25%) was significant after 2-wk of guar treatment compared with the wash-out period. No clinically relevant changes in the safety laboratory parameters were observed during guar treatment. Side effects were observed in 40 of the 93 patients included in the trial. Treatment had to be discontinued in 11% of the patients due to gastrointestinal side effects. On the basis of our results,guar treatment in combination with sulfonylurea and insulin can be recommended for the improvement of carbohydrate and lipid metabolism.

Fatty acid composition of adipose tissue in patients with coronary heart disease.

In order to study the relationship between the fatty acid composition of adipose tissue and coronary heart disease (CHD), 34 consecutive male patients with acute myocardial infarction and 33 hospitalized men free of CHD were compared. Patients with diabetes mellitus, endocrine disorders, liver and kidney diseases, recent changes in body weight and deviations from the "normal", customary diet were exlcuded. A statistically significant difference between the two groups was observed only in stearic acid, its proportion being lower in CHD patients (3.25% vs. 4.13%). Using multivariate discriminant analysis, age discriminated best between the groups, followed by stearic acid. The signs observed were positive for the former and negative for the latter. All other acids, relative body weight, and skinfold measurements did not significantly contribute to the discrimination. Age did not correlate with the proportion of stearic acid. Blood lipids from samples taken within 24 h of admission did not significantly differ between the groups. Three months later they had risen considerably in the infarct patients. The metabolic basis of the relationship between CHD and stearic acid is not clear at present. Additional studies are necessary to substantiate the importance of this acid as an indicator of CHD.

Effect of bezafibrate during 4.5 years of treatment of hyperlipoproteinaemia.

Bezafibrate in a dosage of 200 mg 3 times daily was given to 24 patients with type II A (n = 8), II B (n = 1) and IV (n = 15) hyperlipoproteinaemia for 4.5 years. In type II A the content of total cholesterol and that of low density lipoprotein in serum decreased by 10-23 and 11-34 percent over the years compared to pretreatment. In type IV the content of total triglycerides and that of very low density lipoprotein decreased by 28-39 and 38-52 percent, respectively, over the years. High density lipoprotein cholesterol increased in both types. The "atherogenic index" was reduced by the drug. The effect remained through the 4.5 years of treatment. Compliance to the drug was good. Changes in safety laboratory parameters were minor and reversible. No subjective side-effects occurred and no cases of gallbladder disease or cancer were noted. It is concluded that bezafibrate is a safe, convenient and effective serum lipid-lowering drug suitable for the use in primary and secondary prevention of atherosclerotic disease.

Famciclovir treatment of chronic hepatitis B in heart transplant recipients: a prospective trial.

UNLABELLED: Hepatitis B may take a rapid and aggressive course in patients under immunosuppression. Nucleoside analogues have been shown to suppress viral replication effectively. To investigate the effect of famciclovir in immunosuppressed patients, 21 heart transplant recipients with chronic hepatitis B infection were included in a prospective study. PATIENTS AND METHODS: Patients have been treated with Famciclovir for a median of 14 months. Hepatitis B virus replication and biochemical parameters were regularly tested and liver biopsies were taken before treatment and after a median time of 7 months. HBV-polymerase was sequenced in all patients before therapy and in those patients who experienced virological breakthrough. RESULTS: Nineteen patients were treated for at least 6 months. Hepatitis B virus-DNA levels declined in all patients and became negative in 8 patients. Mean hepatitis B virus-DNA levels decreased from 199+/-269 to 34+/-53 pg/ml after 24 weeks (P=0.003). During treatment HBeAg became negative in five patients. Mean alanine aminotransferase decreased from 42+/-26 to 24+/-10 U/L (P=0.006). Histological analysis revealed improved inflammatory activity according to the Ishak-score in 11/16 (69%) patients. Total inflammatory activity scores decreased from 8 to 6 (median, NS), but interface hepatitis score (P=0.02) and lobular inflammation score (P=0.006) improved significantly. Median fibrosis scores fell from 5 to 3 (P=0.002). Three patients developed virological breakthrough on famciclovir after 7, 8, and 26 months of treatment showing HBV-polymerase amino acid changes L528 M, S567A, and I581K, respectively. CONCLUSIONS: Famciclovir improves not only biochemical and virological features but also hepatic inflammation and liver fibrosis in patients with chronic hepatitis B under heavy immunosuppression. Virological breakthrough may develop and requires close monitoring.