Background paper to the recommendation for routine rotavirus vaccination of infants in Germany.

Two rotavirus (RV) vaccines were introduced to the European market in 2006. To support the decision-making process of the German Standing Committee on Vaccination ("Ständige Impfkommission", STIKO) regarding adoption of routine RV vaccination into the national vaccination schedule in Germany relevant scientific background was reviewed. According to STIKO's Standard Operating Procedures for the development of evidence-based vaccination recommendations, a set of key questions was addressed and systematic reviews were performed with a focus on the efficacy, effectiveness, impact and safety of RV vaccines. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was applied to assess the quality of available evidence. Data from 5 randomized controlled trials demonstrated a high efficacy of RV vaccines in preventing severe RV-associated gastroenteritis (91%) and hospitalization (92%) in settings comparable to Germany. Post-marketing observational studies confirmed these findings. In several countries, impact studies suggest that age groups not eligible for vaccination might also benefit from herd effects and demonstrated a decrease in the number of nosocomial RV infections after RV vaccine introduction. The vaccines were considered safe, except for a slightly increased risk of intussusception shortly after the first dose, corresponding to 1-2 additional cases per 100,000 infants vaccinated (relative risk =1.21, 95% confidence interval [CI] 0.68-2.14). RV case-fatality is extremely low in Germany. However, RV incidence among children aged <5 years is high (reported 8-14 cases per 1000 children annually), and of these almost half require hositalization. In view of the available evidence and expected benefits, STIKO recommends routine rotavirus vaccination of children under the age of 6 months with the main goal of preventing RV-associated hospitalizations in Germany, especially among infants and young children.

[Decision of the Federal Joint Committee on screening for chorionicity - benefit assessment in the absence of screening studies]. / Die Beratungen des Gemeinsamen Bundesausschusses zum Screening auf Chorionizität - Nutzenbewertung beim Fehlen von Screeningstudien.

The main decision-making body of the self-government system in Germany is the Federal Joint Committee (G-BA). In line with the principles of evidence-based medicine, randomised controlled trials with patient-relevant endpoints (in particular mortality, morbidity, quality of life) are preferred for the G-BA assessment of medical treatments and procedures. During this analysis of ultrasound screening for monochorionicity in multiple pregnancies, no studies were identified directly comparing a group with screening vs. a group without screening. Therefore, a 3-step process, which assesses the single components of screening (risk factors, relevant outcome for the patient, existence of a confirmed diagnosis, application of an effective therapy), was used. On the basis of these results the G-BA decided that the statutory health insurance should include the determination of chorionicity in their reimbursement catalogue.

[10 years of assessing prevention and early diagnosis programmes by the Federal Joint Committee of Germany - a methodological analysis]. / Entscheidungen des Gemeinsamen Bundesausschusses zu Früherkennungsuntersuchungen - methodische Analyse der Beschlüsse im Zeitraum 2000 bis 2009.

Medical benefit is the crucial factor in the evidence-based decision-making process of the Federal Joint Committee (G-BA) of Germany. To review the decisions on population-based screening methods from January 2000 to December 2009, we analysed the coverage decisions. During this period of time, the G-BA decided on 14 screening methods, predominantly dealing with the early diagnoses of serious diseases. In 8 cases a positive assessment led to reimbursement by the statutory health insurance funds, in 5 cases the assessment was negative and in one case the conditions were changed. For 7 assessments, a fully reported review was available, 4 of this were positively evaluated. In 2 of these cases, controlled screening studies documented the benefit of the screening method. In another case there was only a case series without a control group. For the fourth method, the question for the benefit of the screening method was divided into 3 sub questions, investigated separately in different studies. The methods of benefit assessments have changed very much over time. A revision of the rules of procedure for the assessment of medical screening methods is advisable.

Selenium in blood, semen, seminal plasma and spermatozoa of stallions and its relationship to sperm quality.

The essential trace element selenium is indispensable for male fertility in mammals. Until now, little data existed regarding the relationship between selenium and sperm quality in the stallion. Selenium, or selenium-dependent glutathione peroxidase activity, was determined in red blood cells, semen, seminal plasma and spermatozoa, and the percentages of spermatozoa with progressive motility (PMS), intact membranes (PMI), altered (positive) acrosomal status (PAS) and detectable DNA damage, determined by the sperm chromatin structure assay, were evaluated in 41 healthy stallions (three samples each). The pregnancy rate per oestrus cycle (PRC) served as an estimation of fertility. An adverse effect on stallion fertility caused by low dietary selenium intake was excluded, as all stallions had sufficient selenium levels in their blood. Interestingly, no significant correlations (P > 0.05) between the selenium level in blood and the selenium level in seminal plasma or spermatozoa were found, suggesting that the selenium level in blood is no indicator of an adequate selenium supply for spermatogenesis. The selenium level in spermatozoa (nmol billion(-1)) was correlated with PMI, PMS and PAS (r = 0.40, r = 0.31 and r = -0.42, respectively; P

Protein expression in the tissues of the cardiovascular system of the rat under selenium deficiency and adequate conditions.

We investigate the effects of selenium in tissues of the cardiovascular system. In order to examine the expression of the heart and aorta proteins (part of them) in the homogenate of selenium-deficient (Se(-)) and selenium control rats (Se(+)), two-dimensional electrophoresis was used by means of giga gels (30 x 35 cm). After electrophoresis, the protein expression pattern of the (Se(-)) gel and (Se(+)) gel was compared. The evaluation of the protein difference was implemented by means of a computer program suitable for the analysis of protein separated by the two-dimensional electrophoresis. In this way more than 2000 proteins a gel (heart) were detected and more than 1900 protein spots were detected in the aorta fraction. Ten significant differences were found between the gel of (Se(+)) and (Se(-)) heart homogenate of the rat and more than 15 significant differences between the gel of (Se(+)) and (Se(-)) of the aorta. By means of MALDI-MS-ESI-MS some of these proteins with different expression levels were not determined until now. Of those, three proteins were detected as the alpha myosin heavy chain (alpha-MHC), myosin light chain 1 and 2 (MLC 1 and 2), and the mitochondrial enzyme creatinine kinase. First results suggest that selenium deficiency affects myocardial energy metabolism and contractile proteins.

Detection and characterization of membrane-bound selenoproteins in the kidney of the rat.

The essential trace element selenium is of fundamental importance to human biology. Information on the membrane-bound selenoproteins was obtained by labeling of rats in vivo with (75)Se-selenite, subcellular fractionation of the tissue homogenates, separation of the proteins by SDS-PAGE, two-dimensional electrophoresis, and selenium detection by autoradiography. In this way, in addition to already known membrane-bound selenoproteins three novel selenoproteins in the molecular mass range of 38-40, 18, and 12-13 kDa were detected in the microsomal membranes.

Detection of small selenium-containing proteins in tissues of the rat.

The important role of selenium in the mammalian organism has been manifested by the detection of several selenoenzymes, and there are still numerous selenium-containing proteins to be identified. After in vivo labeling of rats with [75Se]-selenite, gel electrophoretic separation of the proteins in tissue homogenates and autoradiography of the labeled bands, information on the selenium-containing proteins present in the different tissues was obtained. In the separation by SDS-PAGE and two-dimensional IEF/SDS-PAGE a large number of selenium-containing proteins or protein subunits with apparent molecular masses in the range from 116 to 8 kDa could be distinguished. This range was extended by applying a modified Tricine-SDS-PAGE, which allows the determination of smaller proteins. Using this method in the separation of the homogenates of the adrenal, brain, diaphragm, epididymis, heart, kidney, liver, lung, pituitary, prostate, skeletal muscle, spleen, thymus and thyroid, four additional selenium-containing proteins with molecular masses of approximately 7 kDa, 5kDa, 4 kDa and 3kDa were detected. The 5 kDa protein and the 7 kDa protein were identified as selenocysteine-containing selenoproteins.