Exhalomics as a noninvasive method for assessing rumen fermentation in dairy cows: Can exhaled-breath metabolomics replace rumen sampling?

Previously, we used secondary electrospray ionization-mass spectrometry (SESI-MS) to investigate the diurnal patterns and signal intensities of exhaled (EX) volatile fatty acids (VFA) of dairy cows. The current study aimed to validate the potential of an exhalomics approach for evaluating rumen fermentation. The experiment was conducted in a switchback design, with 3 periods of 9 d each, including 7 d for adaptation and 2 d for sampling. Four rumen-cannulated original Swiss Brown (Braunvieh) cows were randomly assigned to 1 of 2 diet sequences (ABA or BAB): (A) low starch (LS; 6.31% starch on a dry matter basis) and (B) high starch (HS; 16.2% starch on a dry matter basis). Feeding was once per day at 0830 h. Exhalome (with the GreenFeed System), and rumen samples were collected 8 times to represent every 3 h of a day, and EX-VFA and ruminal (RM)-VFA were analyzed using SESI-MS and HPLC, respectively. Furthermore, the VFA concentration in the gas phase (HR-VFA) was predicted based on RM-VFA and Henry's Law (HR) constants. No interactions were identified between the types of diets (HS vs. LS) and the measurement methods on daily average VFA profiles (RM vs. EX or HR vs. EX), suggesting a consistent performance among the methods. Additionally, when the 3-h interval VFA data from HS and LS diets were analyzed separately, no interactions were observed between methods and time of day, indicating that the relative daily pattern of VFA molar proportions was similar regardless of the VFA measurement method used. The results revealed that the levels of acetate sharply increased immediately after feeding, trailed by an increase in the acetate:propionate ratio and a steady increase for propionate (2 h after feeding the HS diet, 4 h for LS), and butyrate. This change was more pronounced for the HS diet than the LS diet. However, there was no overall diet effect on the VFA molar proportions, although the measurement methods affected the molar proportions. Furthermore, we observed a strong positive correlation between the levels of RM and EX acetate for both diets (HS: r = 0.84; LS: r = 0.85), RM and EX propionate (r = 0.74), and RM and EX acetate:propionate ratio (r = 0.80). Both EX-VFA and RM-VFA exhibited similar responses to feeding and dietary treatments, suggesting that EX-VFA could serve as a useful proxy for characterizing RM-VFA molar proportions to evaluate rumen fermentation. Similar relationships were observed between RM-VFA and HR-VFA. In conclusion, this study underscores the potential of exhalomics as a reliable approach for assessing rumen fermentation. Moving forward, research should further explore the depth of exhalomics in ruminant studies to provide a comprehensive insight into rumen fermentation metabolites, especially across diverse dietary conditions.

Effects of graded levels of dietary pomegranate peel on methane and nitrogen losses, and metabolic and health indicators in dairy cows.

This study aimed to quantify the effects of dietary inclusion of tannin-rich pomegranate peel (PP) on intake, methane and nitrogen (N) losses, and metabolic and health indicators in dairy cows. Four multiparous, late-lactating Brown Swiss dairy cows (796 kg body weight; 29 kg/d of energy corrected milk yield) were randomly allocated to 3 treatments in a randomized cyclic change-over design with 3 periods, each comprising 14 d of adaptation, 7 d of milk, urine, and feces collection, and 2 d of methane measurements. Treatments were formulated using PP that replaced on a dry matter (DM) basis 0% (control), 5%, and 10% of the basal mixed ration (BMR) consisting of corn and grass silage, alfalfa, and concentrate. Gaseous exchange of the cows was determined in open-circuit respiration chambers. Blood samples were collected on d 15 of each period. Individual feed intake as well as feces and urine excretion were quantified, and representative samples were collected for analyses of nutrients and phenol composition. Milk was analyzed for concentrations of fat, protein, lactose, milk urea N, and fatty acids. Total phenols and antioxidant capacity in milk and plasma were determined. In serum, the concentrations of urea and bilirubin as well as the activities of alanine aminotransferase (ALT), aspartate aminotransferase, glutamate dehydrogenase, alkaline phosphatase, and γ-glutamyl transferase were measured. The data were subjected to ANOVA with the Mixed procedure of SAS, with treatment and period as fixed and animal as random effects. The PP and BMR contained 218 and 3.5 g of total extractable tannins per kg DM, respectively, and thereof 203 and 3.3 g of hydrolyzable tannins. Total DM intake, energy corrected milk, and methane emission (total, yield, and intensity) were not affected by PP supplementation. The proportions of C18:2n-6 and C18:3n-3 in milk increased linearly as the amount of PP was increased in the diet. Milk urea N, blood urea N, and urinary N excretion decreased linearly with the increase in dietary PP content. Total phenols and antioxidant capacity in milk and plasma were not affected by the inclusion of PP. The activity of ALT increased in a linear manner with the inclusion of PP. In conclusion, replacing up to 10% of BMR with PP improved milk fatty acid composition and alleviated metabolic and environmental N load. However, the elevated serum ALT activity indicates an onset of liver stress even at 5% PP, requiring the development of adaptation protocols for safe inclusion of PP in ruminant diets.

Transfer of total phenols from a grapeseed-supplemented diet to dairy sheep and goat milk, and effects on performance and milk quality.

Polyphenols are known to affect digestion of ruminants, whereas there is little information about their metabolic effects. In a 2 × 2-factorial experiment the effects of supplementing a phenolic grapeseed extract were compared in 11 East Friesian dairy sheep and 9 Saanen goats. The concentrate supplemented with 7.4 g/100 g DM grapeseed extract had contents of 3.5 g additional phenols/100 g DM and was compared with a low phenolic control concentrate. Performance, total phenols in blood, milk, urine and feces, antioxidant capacity of the blood, and saliva properties were examined. The experiment lasted for 11 wk from parturition to late lactation, with an initial adaptation phase of 1 wk. Milk yield was measured daily after weaning at about 7 wk after parturition. Blood, milk, saliva, feces and urine were sampled 4, 3, 2, 2 and 2 times per animal, respectively. The phenolic diet increased phenol concentrations in blood (+10% and 17% in wk 5 and wk 11, respectively) and in milk (+32% in wk 5) on some of the sampling weeks. There were no clear species differences in phenol concentrations in blood plasma, milk, urine and feces. However, at the end of the experiment the supplemented goats had a higher (48%) urinary phenol concentrations than the non-supplemented goats. A weak relationship (P < 0.05) was found between phenol intake and phenol excretion with milk for sheep but not goats. The phenolic diet did not influence blood antioxidant capacity and tannin binding capacity of the saliva. The saliva of the goats had a higher tannin binding capacity than sheep saliva. The effects of the extract on milk yield were inconsistent between sheep and goats. In general, goats had higher feed and nutrient intakes, were heavier, and yielded more milk. Additionally, milk protein and lactose contents were lower and milk urea content was higher in goats than sheep. In conclusion, supplementing grapeseed extract to sheep and goats elevated phenol concentrations in milk and blood to a certain extent, but most of the phenols were lost via urine. The study gave another indication that goats seem to have developed coping mechanisms like a higher salivary tannin binding capacity, mechanisms which are less pronounced in sheep.

Emergence of tick-borne encephalitis in new endemic areas in Austria: 42 years of surveillance.

Human infections with tick-borne encephalitis (TBE)virus are a public health concern in certain regions of Europe, central and eastern Asia. Expansions of endemic areas and increased incidences have been associated with different factors including ecological changes supporting tick reproduction, socioeconomic changes increasing human outdoor activities and climatic changes favouring virus circulation in natural foci. Austria is among the most strongly affected countries in Central Europe, but the annual number of cases has strongly declined due to vaccination. Here,we have analysed changes of the incidence of TBE in the unvaccinated population of all federal states of Austria over a period of 42 years. The overall incidence in Austria has remained constant, but new strongly affected endemic regions have emerged in alpine valleys in the west of Austria. In parallel, the incidence in low-land regions in the north-east of the country is decreasing. There is no evidence for a shift to higher altitudes of infection sites in the traditional TBE zones,but the average altitudes of some newly established endemic areas in the west are significantly higher. Our analyses underscore the focal nature of TBE endemic areas and the potential of TBE virus to emerge in previously unaffected regions.

Phase III trial of bortezomib, cyclophosphamide and dexamethasone (VCD) versus bortezomib, doxorubicin and dexamethasone (PAd) in newly diagnosed myeloma.

We aimed at demonstrating non-inferiority of bortezomib/cyclophosphamide/dexamethasone (VCD) compared to bortezomib/doxorubicin/dexamethasone (PAd) induction therapy with respect to very good partial response rates or better (⩾VGPR) in 504 newly diagnosed, transplant-eligible multiple myeloma patients. VCD was found to be non-inferior to PAd with respect to ⩾VGPR rates (37.0 versus 34.3%, P=0.001). The rates of progressive disease (PD) were 0.4% (VCD) versus 4.8% (PAd; P=0.003). In the PAd arm, 11 of 12 patients with PD had either renal impairment (creatinine ⩾2 mg/dl) at diagnosis or the cytogenetic abnormality gain 1q21, whereas no PD was observed in these subgroups in the VCD arm. Leukocytopenia/neutropenia (⩾3°) occurred more frequently in the VCD arm (35.2% versus 11.3%, P<0.001). Neuropathy rates (⩾2°) were higher in the PAd group (14.9 versus 8.4%, P=0.03). Serious adverse events, both overall and those related to thromboembolic events, were higher in the PAd group (32.7 versus 24.0%, P=0.04 and 2.8 versus 0.4%, P=0.04). Stem cell collection was not impeded by VCD. VCD is as effective as PAd in terms of achieving ⩾VGPR rates with fewer PD and has a favorable toxicity profile. Therefore, VCD is preferable to PAd as induction therapy.

The application of Gadopentate-Dimeneglumin has no impact on progression free and overall survival as well as renal function in patients with monoclonal plasma cell disorders if general precautions are taken.

OBJECTIVES: The current analysis investigated the prognostic significance of gadopentetate dimeglumine on survival and renal function in patients with monoclonal plasma cell disorders. METHODS: In this study 263 patients who had received gadopentetate dimeglumine within a prospective trial investigating dynamic contrast-enhanced magnetic resonance imaging (MRI) were compared with 335 patients who had undergone routine, unenhanced MRI. RESULTS: We found no significant prognostic impact of the application of contrast agent on progression-free survival in patients with either monoclonal gammopathy of undetermined significance, smouldering or symptomatic myeloma and no significant prognostic impact on overall survival in patients with symptomatic myeloma. Since renal impairment is a frequent complication of myeloma, and decreased renal function is associated with a higher risk of complications in patients receiving contrast agents, we evaluated the impact of contrast agent on renal function after 1 year. In the present analysis the only significant adverse impact on kidney function occurred in symptomatic myeloma patients who already had impaired renal parameters at baseline. Here, the renal function did not recover during therapy, whereas it did so in patients with normal or only slightly impaired renal function. CONCLUSION: If general recommendations are adhered to, gadopentetate dimeglumine can be safely applied in patients with monoclonal plasma cell disease.

Osteo-odonto-keratoprosthesis (OOKP) and the testing of three different adhesives for bonding bovine teeth with optical poly-(methyl methacrylate) (PMMA) cylinder.

AIM: Preparation of the lamina during osteo-odonto-keratoprosthesis (OOKP) design is complex, and its longevity and watertightness important. To date, only acrylic bone cements have been used for bonding the optical cylinder to the tooth dentine. Our aim was to evaluate different dental adhesives for OOKP preparation. METHODS: Specimens of bovine teeth were produced by preparing 1.5-mm thick dentine slices with holes having a diameter of 3.5 mm. Each group (n=10 per group) was luted with either classic poly-(methyl methacrylate) (PMMA) bone cement, universal resin cement or glass ionomer cement. All specimens underwent force measurement using a uniaxial traction machine. RESULTS: The highest mean force required to break the bond was measured for PMMA bone cement (128.2 N) followed by universal resin cement (127.9 N), with no statistically significant difference. Glass ionomer cement showed significantly lower force resistance (78.1 N). CONCLUSIONS: Excellent bonding strength combined with easy application was found for universal resin cement, and thus, it is a potential alternative to acrylic bone cement in OOKP preparation.

Tumour-site-dependent expression profile of angiogenic factors in tumour-associated stroma of primary colorectal cancer and metastases.

BACKGROUND: Tumour-associated stroma has a critical role in tumour proliferation. Our aim was to determine a specific protein expression profile of stromal angiogenic cytokines and matrix metalloproteinases (MMPs) to identify potential biomarkers or new therapy targets. METHODS: Frozen tissue of primary colorectal cancer (n=25), liver (n=25) and lung metastases (n=23) was laser-microdissected to obtain tumour epithelial cells and adjacent tumour-associated stroma. Protein expression of nine angiogenic cytokines and eight MMPs was analysed using a multiplex-based protein assay. RESULTS: We found a differential expression of several MMPs and angiogenic cytokines in tumour cells compared with adjacent tumour stroma. Cluster analysis displayed a tumour-site-dependent stromal expression of MMPs and angiogenic cytokines. Univariate analysis identified stromal MMP-2 and MMP-3 in primary colorectal cancer, stromal MMP-1, -2, -3 and Angiopoietin-2 in lung metastases and stromal MMP-12 and VEGF in liver metastases as prognostic markers (P>0.05, respectively). Furthermore, stroma-derived Angiopoietin-2 proved to be an independent prognostic marker in colorectal lung metastases. CONCLUSION: Expression of MMPs and angiogenic cytokines in tumour cells and adjacent tumour stroma is dependent on the tumour site. Stroma-derived MMPs and angiogenic cytokines may be useful prognostic biomarkers. These data can be helpful to identify new agents for a targeted therapy in patients with colorectal cancer.

Autologous stem cell transplantation for elderly patients with newly diagnosed multiple myeloma in the era of novel agents.

BACKGROUND: High-dose therapy (HDT) with autologous stem cell transplantation (ASCT) is considered the standard of care for multiple myeloma (MM) patients <65 years. Safety and outcome of ASCT for patients >65 years is currently uncertain, especially since the introduction of novel agents for induction and maintenance therapy. Furthermore, there are no conclusive data available on risk assessment in elderly patients treated with HDT. PATIENTS AND METHODS: We retrospectively analyzed 202 patients ≥60 years with newly diagnosed MM who underwent ASCT at our institution. Patients were stratified by age into three groups (60-64, 65-69 and 70-75 years). For safety assessment, we compared data about hospitalization, hematopoetic reconstitution and early mortality. Remission before and after ASCT was analyzed according to age and application of novel agents. Event-free (EFS) and overall survival (OS) were analyzed to identify impact of age, remission before/after ASCT and maintenance therapy as well as ISS score and cytogenetic aberrations on outcome in elderly patients. RESULTS: The assessment of safety, remission before/after ASCT as well as EFS and OS showed no significant differences between the three groups (median EFS: 60-64 years: 27 months; 65-69 years: 23 months; 70-75 years: 23 months; median OS: not reached). Patients receiving novel agents as part of induction therapy achieved significantly higher nCR + CR rates than patients treated without novel agents. In Cox regression analysis, ISS and cytogenetics as well as remission after ASCT had the highest prognostic impact on EFS and OS. Maintenance therapy was associated with longer EFS in uni- and multivariate analyses. CONCLUSION: ASCT is feasible for selected patients >65 and >70 years without increased mortality. Age at transplantation has no prognostic significance on outcome after ASCT. Novel agents during induction therapy and maintenance therapy improves outcome of older patients eligible for ASCT. ISS and cytogenetic analysis should be carried out routinely for risk assessment.

Risk factors and containment of respiratory syncytial virus outbreak in a hematology and transplant unit.

Respiratory syncytial virus (RSV) usually causes self-limiting upper respiratory tract infections, but can be associated with severe lower respiratory tract infection disease (LRTID) in infants and in patients with hematologic malignancies. We have analyzed the risk factors and the measures for containment within an outbreak of nosocomial RSV infections in a hematology and SCT unit. A total of 56 patients were affected (53 RSV-A and 3 RSV-B) including 32 transplant patients (16 allogeneic and 16 autologous). Forty (71%) of the 56 patients suffered from LRTID and 14 (35%) of the patients with LRTID subsequently died. However, because of concomitant infections with fungal and bacterial pathogens, the impact of RSV on the fatal outcome was difficult to assess. Multivariate analysis showed that low levels of IgG were significantly associated with fatal outcome (P=0.007), treatment with oral ribavirin represented a protective factor (P=0.02). An extremely protracted viral shedding was observed in this cohort of patients (median=30.5 days, range: 1-162 days), especially pronounced in patients after allogeneic transplantation (P=0.002). Implementation of rigorous isolation and barrier measures, although challenged by long-term viral carriers, was effective in containment of the outbreak.

Effects of lunch on children's short-term cognitive functioning: a randomized crossover study.

BACKGROUND/OBJECTIVES: Considering the large number of children worldwide attending all-day schools, information on the effects of lunch on short-term cognitive performance is of public health relevance. However, only adult studies investigated this issue yet. Therefore, this study examined the impact of skipping lunch vs having lunch on children's cognitive functioning in the early afternoon. SUBJECTS/METHODS: Participants in this randomized crossover study with two groups were healthy 6th grade students of an all-day school in Gelsenkirchen, Germany. Group 1 skipped lunch on study day 1 and received an ad libitum lunch 1 week later on study day 2. The order for group 2 was vice versa. In the afternoon tonic alertness, visuospatial memory and selective attention were determined using a computerized test battery of the Vienna Test System. For continuous and discrete interval-scaled variables, treatment effect was estimated using the two sample t-test or the Wilcoxon rank-sum test, for discrete ordinal-scaled variables using generalized linear models. RESULTS: Data on 105 children (48% male; 12.6 ± 0.6 years) were analyzed. Except for tonic alertness there were no significant differences in cognitive functioning between the skipping lunch day and the having lunch day. The higher number of omission errors on the skipping lunch day lost significance when adjusting for multiple testing. CONCLUSIONS: In the first study on this topic lunch did not have relevant effects on children's cognitive functioning in the early afternoon. Future research needs to be done to figure out potential methodical and physiological explanations.

Determinants of heart failure self-care behaviour in community-based patients: a cross-sectional study.

BACKGROUND: Self-care behaviour in patients with heart failure (HF) represents a series of specific actions that patients should take, as an important treatment component. AIMS: The aim of this study was to identify potential determinants of HF self-care in ambulatory patients with stable systolic HF. METHODS: In a cross-sectional study of 318 patients with chronic systolic HF recruited in 48 German primary care practices, we evaluated the patient-reported European HF Self-care Behaviour scale (EHFScBs) assessments (range 12-60, where lower scores indicate better self-care). Potential determinants included socio-demographic (e.g. age, living status), clinical (e.g. NYHA class, LVEF, NT-proBNP levels, co-morbidities), behavioural (e.g. smoking and alcohol intake), psychosocial (SF-36 scales and KCCQ domains, e.g. quality of life and self-efficacy) and depression status (PHQ-D), plus previous health care utilisation. Mixed regression modelling was applied. RESULTS: Patients had a mean (SD) age of 69.0 (10.4) years and were 71% male. They had a good overall EHFScBs score of 24.7 (7.8) (n=274). In the final regression model (n=271), six determinants were retained (ß; descriptive p-value): self-efficacy (-0.24; <.001), age (-0.22; <.001), prosthetic heart valve (-0.14; .01), referrals to cardiologists (-0.14; .02), peripheral arterial disease (0.13; .03) and quality of life (0.16; .02). CONCLUSION: In this exploratory cross-sectional study, the potential non-modifiable and modifiable risk factors and resources involved in patients' HF self-care were at the individual and organisational level. Self-efficacy and quality of life are potentially modifiable, so these could be targeted for improvement by enhancing patient motivation, HF education and further supporting a collaborative care approach.

Flat Refractive Geometry.

While the study of geometry has mainly concentrated on single viewpoint (SVP) cameras, there is growing attention to more general non-SVP systems. Here, we study an important class of systems that inherently have a non-SVP: a perspective camera imaging through an interface into a medium. Such systems are ubiquitous: They are common when looking into water-based environments. The paper analyzes the common flat-interface class of systems. It characterizes the locus of the viewpoints (caustic) of this class and proves that the SVP model is invalid in it. This may explain geometrical errors encountered in prior studies. Our physics-based model is parameterized by the distance of the lens from the medium interface, besides the focal length. The physical parameters are calibrated by a simple approach that can be based on a single frame. This directly determines the system geometry. The calibration is then used to compensate for modeled system distortion. Based on this model, geometrical measurements of objects are significantly more accurate than if based on an SVP model. This is demonstrated in real-world experiments. In addition, we examine by simulation the errors expected by using the SVP model. We show that when working at a constant range, the SVP model can be a good approximation.

The potential impact of nutrient profiles on dairy-related energy and nutrient intake in German children and adolescents.

BACKGROUND/OBJECTIVES: To evaluate the potential impact of nutrient profiling-based dairy product choices on energy and nutrient intake in German children and adolescents. SUBJECTS/METHODS: Consumption data were obtained from product-specific dietary records in the DONALD Study (Dortmund Nutritional and Anthropometric Longitudinally Designed Study). We compared actual intake data with intake data that were calculated based on the assumption that participants exclusively consumed products that met the criteria of selected nutrient profiling models. RESULTS: For most profiling models, the percentage of compliant products was unrelated to the percentage of the participants' dairy consumption rated eligible. The participants' intake of energy, saturated fatty acids (SAFA), sodium, calcium and vitamin D would be reduced significantly (P<0.0001) if only qualifying products were consumed. The impact on the participants' nutrient intake levels was not directly related to the impact on the product's nutrient content levels. Lower fat consumption was correlated with reduced vitamin D intake, and the models' disqualification of (semi-) hard cheeses had a negative impact on the calcium intake. CONCLUSIONS: The evaluation of product-specific intake data was critical to understand the potential impact of any profiling scheme on nutrient intake. Selecting dairy products based on nutrient profiling could help reduce the intake of less-desirable nutrients, such as SAFA and sodium. However, models that are too restrictive might negatively impact calcium and vitamin D intake. Ultimately, the effectiveness of nutrient profiling models will be determined by the fact whether or not complying foods are consumed.

Intracranial application of free fasciocutaneous flaps in a novel sandwich technique for skull base reconstruction.

Free tissue transfer has been the gold standard of extensive skull base reconstruction, but the onlay of free flaps onto skull base defects carries the risk of cerebrospinal fluid (CSF) leakage. The purpose of this study was the evaluation of a novel technique of a combined sub- and onlay concept with a partially intracranially positioned folded free fasciocutaneous flap in terms of flap applicability, versatility and complication rate. Within 5 years, 7 patients with anterior (n=4), middle (n=2) or posterior (n=1) skull base defects were reconstructed with free extended lateral arm (n=3) or anterolateral thigh (n=4) flaps. The flaps were partially intracranially positioned and fixed with osteo-dermal sutures. Both flaps proved to be applicable in terms of sealing efficiency, minimizing intracranial flap volume and folding. No flap loss was observed. Specific complications consisted of one pneumocranium via an accessory frontal sinus and one cerebellar herniation due to lumbar CSF loss. No flap failure or haematoma of the intracranial flap part occurred. This new concept of intracranial positioning of fasciocutaneous flaps in a sandwich technique using osteo-dermal sutures should be considered as a primary treatment for skull base reconstruction rather than merely as a salvage manoeuvre.

Nutrient profiling and food label claims: evaluation of dairy products in three major European countries.

BACKGROUND/OBJECTIVES: This study reviews commercially available dairy products with nutrition or health-related on-pack communication against selected nutrient profiling models. It aims to provide guidance on the model characteristics required to appropriately categorise products into those that are suitable for carrying claims, versus those whose overall nutritional composition does not support such product communication. SUBJECTS/METHODS: More than 300 dairy products carrying claims were identified in Germany, France and the UK and evaluated against six existing nutrient profiling models. All models were assessed regarding their underlying principles, generated results and inter-model agreement levels. RESULTS: In most cases, products failed the criteria of a given model because of too high levels of total fat, saturated fatty acids, sugars and/ or sodium. The Swedish Keyhole and the Smart Choices Program were the most restrictive models and showed the highest level of agreement. In general, the application of nutrient profiles helped to select products with significantly lower average levels of nutrients that are linked to chronic diseases when consumed in excess. However, calcium levels were also highly impacted in some cases. CONCLUSIONS: A nutrient profiling model that targets saturated fatty acids, sugars and sodium can meaningfully and comprehensively identify dairy products with a favourable nutritional composition. However, thresholds have to be set carefully to not reduce the average calcium contribution of the category. The use of separate criteria for cheeses and other dairy products seems necessary to take into account intrinsic compositional differences.

[The ABC's of medical statistics. Reading and understanding clinical trials]. / Das ABC der medizinischen Statistik.

Clinical trials test hypotheses that are accepted or rejected according to a predetermined probability of error (level of significance). Significance does not however mean relevance. Good parameters of relevance are absolute risk reduction and based on this the calculation of the number of patients who need to be treated for one additional patient to benefit. The randomized controlled trial is the gold standard for comparative evaluation of effects. In the ideal scenario it is designed so that a difference established by statistical methods becomes probable. In non-inferiority studies care should be taken that no equivalence is shown but rather that the difference is not greater than a predefined margin of error for differences. Meta-analyses of studies with similar endpoints have the potential to improve the level of evidence. Since the findings of meta-analyses depend on the studies included, critical assessment of the results is essential.

[ The ABC's of medical statistics. Reading and understanding clinical trials]. / Das ABC der medizinischen Statistik. Klinische Studien lesen und verstehen.

Clinical trials test hypotheses that are accepted or rejected according to a predetermined probability of error (level of significance). Significance does not however mean relevance. Good parameters of relevance are absolute risk reduction and based on this the calculation of the number of patients who need to be treated for one additional patient to benefit. The randomized controlled trial is the gold standard for comparative evaluation of effects. In the ideal scenario it is designed so that a difference established by statistical methods becomes probable. In non-inferiority studies care should be taken that no equivalence is shown but rather that the difference is not greater than a predefined margin of error for differences. Meta-analyses of studies with similar endpoints have the potential to improve the level of evidence. Since the findings of meta-analyses depend on the studies included, critical assessment of the results is essential.

[The ABC's of medical statistics. Reading and understanding clinical trials]. / Das ABC der medizinischen Statistik. Klinische Studien lesen und verstehen.

Clinical trials test hypotheses that are accepted or rejected according to a predetermined probability of error (level of significance). Significance does not however mean relevance. Good parameters of relevance are absolute risk reduction and based on this the calculation of the number of patients who need to be treated for one additional patient to benefit. The randomized controlled trial is the gold standard for comparative evaluation of effects. In the ideal scenario it is designed so that a difference established by statistical methods becomes probable. In non-inferiority studies care should be taken that no equivalence is shown but rather that the difference is not greater than a predefined margin of error for differences. Meta-analyses of studies with similar endpoints have the potential to improve the level of evidence. Since the findings of meta-analyses depend on the studies included, critical assessment of the results is essential.