Quality of life in high-risk patients: comparison of transcatheter aortic valve implantation with surgical aortic valve replacement

OBJECTIVES To compare health-related quality of life (QoL) in patients undergoing transcatheter aortic valve implantation via transapical access (TA TAVI) with patients undergoing surgical aortic valve replacement (SAVR). METHODS One hundred and forty-four high-risk patients referred for aortic valve replacement underwent TAVI screening and were assigned to either TA TAVI (n = 51, age 79.7 ± 9.2 years, logistic EuroSCORE 26.5 ± 16.1%, 51% males) or SAVR (n = 93, age 81.1 ± 5.3 years, logistic EuroSCORE 12.1 ± 9.3%, 42% males) by the interdisciplinary heart team. QoL was assessed using the Short Form 36 (SF-36) Health Survey Questionnaire and the Hospital Anxiety and Depression Scale. Furthermore, current living conditions and the degree of independence at home were evaluated. RESULTS Patients undergoing TA TAVI were at higher risk as assessed by EuroSCORE (26.5 ± 16 vs. 12.1 ± 9, P < 0.001) and STS score (6.7 ± 4 vs. 4.4 ± 3, P < 0.001) compared with SAVR patients. At the 30-day follow-up, the rate of mortality was similar and amounted to 7.8% for TA TAVI and 7.5% for SAVR patients and raised to 25.5% in TA TAVI and 18.3% in SAVR patients after a follow-up period of 15 ± 10 months. Assessment of QoL revealed no differences in terms of anxiety and depression between TA TAVI and SAVR patients. The SF-36 mental health metascore was similar in both groups (65.6 ± 19 vs. 68.8 ± 22, P = 0.29), while a significant difference was observed in the physical health metascore (49.7 ± 21 vs. 62.0 ± 21, P = 0.015). After adjustment for baseline characteristics, this difference disappeared. However, every added point in the preoperative risk assessment with the STS score decreased the SF-36 physical health dimension by two raw points at the follow-up assessment. CONCLUSIONS Selected high-risk patients undergoing TAVI by using a transapical access achieve similar clinical outcomes and QoL compared with patients undergoing SAVR. Increased STS scores predict worse QoL outcomes.

The future of osteoporosis treatment - a research update

Osteoporosis is characterised by a progressive loss of bone mass and microarchitecture which leads to increased fracture risk. Some of the drugs available to date have shown reductions in vertebral and non-vertebral fracture risk. However, in the ageing population of industrialised countries, still more fractures happen today than are avoided, which highlights the large medical need for new treatment options, models, and strategies. Recent insights into bone biology, have led to a better understanding of bone cell functions and crosstalk between osteoblasts, osteoclasts, and osteocytes at the molecular level. In the future, the armamentarium against osteoporotic fractures will likely be enriched by (1.) new bone anabolic substances such as antibodies directed against the endogenous inhibitors of bone formation sclerostin and dickkopf-1, PTH and PTHrp analogues, and possibly calcilytics; (2.) new inhibitors of bone resorption such as cathepsin K inhibitors which may suppress osteoclast function without impairing osteoclast viability and thus maintain bone formation by preserving the osteoclast-osteoblast crosstalk, and denosumab, an already widely available antibody against RANKL which inhibits osteoclast formation, function, and survival; and (3.) new therapeutic strategies based on an extended understanding of the pathophysiology of osteoporosis which may include sequential therapies with two or more bone active substances aimed at optimising the management of bone capital acquired during adolescence and maintained during adulthood in terms of both quantity and quality. Finally, one of the future challenges will be to identify those patients and patient populations expected to benefit the most from a given drug therapy or regimen. The WHO fracture risk assessment tool FRAX® and improved access to bone mineral density measurements by DXA will play a key role in this regard.

Are mutans streptococci detected in preschool children a reliable predictive factor for dental caries risk? A systematic review

Research suggests that mutans streptococci play an important role in cariogenesis in children but the usefulness of bacterial testing in risk assessment is unknown. Our objective was to summarize the literature assessing the association of mutans streptococci and dental caries in preschool children, (Pre)Medline (1966-2003), Embase (1980-2003), the Cochrane Register of Controlled Trials (2003, issue 3), and reference lists of included studies were searched. All abstracts found by the electronic searches (n = 981) were independently scrutinized by 2 reviewers. Minimal requirements for inclusion were assessment of preschool children without caries at baseline, reporting of mutans streptococci present in saliva or plaque at baseline and assessment of caries presence after a minimum of 6 months of follow-up. Participants' details, test methods, methodological characteristics and findings were extracted by one reviewer and cross-checked by another. Homogeneity was tested using chi2 tests. Results of plaque and saliva testing were pooled separately using a fixed effects model. Methodological quality of reports was low. Out of 9 studies included, data from 3 reports on plaque test assessment alone (n = 300) and from 4 reports on saliva test assessment alone (n = 451) were available for pooled analysis. The pooled risk ratio (95% CI) was 3.85 (2.48-5.96) in studies using plaque tests and 2.11 (1.47-3.02) in those using saliva testing. Presence of mutans streptococci, both in plaque or saliva of young caries-free children, appears to be associated with a considerable increase in caries risk. Lack of adjustment for potential confounders in the original studies, however, limits the extent to which interpretations for practice can be made.

First trimester markers for pre-eclampsia: placental vs. non-placental protein serum levels

BACKGROUND/AIM: Parallel investigation, in a matched case-control study, of the association of different first-trimester markers with the risk of subsequent pre-eclampsia (PE). METHOD: The levels of different first trimester serum markers and fetal nuchal translucency thickness were compared between 52 cases of PE and 104 control women by non-parametric two-group comparisons and by calculating matched odds ratios. RESULTS: In univariable analysis increased concentrations of inhibin A and activin A were associated with subsequent PE (p < 0.02). Multivariable conditional logistic regression models revealed an association between increased risk of PE and increased inhibin A and translucency thickness and respectively reduced pregnancy-associated plasma protein A (PAPP-A) and placental lactogen . However, these associations varied with the gestational age at sample collection. For blood samples taken in pregnancy weeks 12 and 13 only, increased levels of activin A, inhibin A and nuchal translucency thickness, and lower levels of placenta growth factor and PAPP-A were associated with an increased risk of PE. CONCLUSIONS: Members of the inhibin family and to some extent PAPP-A and placental growth factor are superior to other serum markers, and the predictive value of these depends on the gestational age at blood sampling. The availability of a single, early pregnancy 'miracle' serum marker for PE risk assessment seems unlikely in the near future.

Prosthetic treatment planning on the basis of scientific evidence

The objective of this report is to summarize the results on survival and complication rates of different designs of fixed dental prostheses (FDP) published in a series of systematic reviews. Moreover, the various parameters for survival and risk assessment are to be used in attempt to perform treatment planning on the basis of scientific evidence. Three electronic searches complemented by manual searching were conducted to identify prospective and retrospective cohort studies on FDP and implant-supported single crowns (SC) with a mean follow-up time of at least 5 years. Patients had to have been examined clinically at the follow-up visit. Failure and complication rates were analyzed using random-effects Poisson regression models to obtain summary estimates of 5- and 10-year survival proportions. Meta-analysis of the studies included indicated an estimated 5-year survival of conventional tooth-supported FDP of 93.8%, cantilever FDP of 91.4%, solely implant-supported FDP of 95.2%, combined tooth-implant-supported FDP of 95.5% and implant-supported SC of 94.5% as well as resin-bonded bridges 87.7%. Moreover, after 10 years of function the estimated survival decreased to 89.2% for conventional FDP, to 80.3% for cantilever FDP, to 86.7% for implant-supported FDP, to 77.8% for combined tooth-implant-supported FDP, to 89.4% for implant-supported SC and to 65% for resin-bonded bridges. When planning prosthetic rehabilitations, conventional end-abutment tooth-supported FDP, solely implant-supported FDP or implant-supported SC should be the first treatment option. Only as a second option, because of reasons such as financial aspects patient-centered preferences or anatomical structures cantilever tooth-supported FDP, combined tooth-implant-supported FDP or resin-bonded bridges should be chosen.

Risk scoring for setting priorities in a monitoring of antimicrobial resistance in meat and meat products

Meat and meat products can be contaminated with different species of bacteria resistant to various antimicrobials. The human health risk of a type of meat or meat product carry by emerging antimicrobial resistance depends on (i) the prevalence of contamination with resistant bacteria, (ii) the human health consequences of an infection with a specific bacterium resistant to a specific antimicrobial and (iii) the consumption volume of a specific product. The objective of this study was to compare the risk for consumers arising from their exposure to antibiotic resistant bacteria from meat of four different types (chicken, pork, beef and veal), distributed in four different product categories (fresh meat, frozen meat, dried raw meat products and heat-treated meat products). A semi-quantitative risk assessment model, evaluating each food chain step, was built in order to get an estimated score for the prevalence of Campylobacter spp., Enterococcus spp. and Escherichia coli in each product category. To assess human health impact, nine combinations of bacterial species and antimicrobial agents were considered based on a published risk profile. The combination of the prevalence at retail, the human health impact and the amount of meat or product consumed, provided the relative proportion of total risk attributed to each category of product, resulting in a high, medium or low human health risk. According to the results of the model, chicken (mostly fresh and frozen meat) contributed 6.7% of the overall risk in the highest category and pork (mostly fresh meat and dried raw meat products) contributed 4.0%. The contribution of beef and veal was of 0.4% and 0.1% respectively. The results were tested and discussed for single parameter changes of the model. This risk assessment was a useful tool for targeting antimicrobial resistance monitoring to those meat product categories where the expected risk for public health was greater.

Effects of native pollinator specialization, selfcompatibility and flowering duration of European plant species on their invasiveness elsewhere

1. When entomophilous plants are introduced to a new region, they may leave behind their usual pollinators. In particular, plant species with specialized pollination may then be less likely to establish and spread (i.e. become invasive). Moreover, other reproductive characteristics such as self-compatibility and flowering duration may also affect invasion success. 2. Here, we specifically asked whether plant species' specialization towards pollinator species and families, respectively, as measured in the native range, self-compatibility, flowering duration and their interactions are related to the degree of invasion (i.e. a measure of regional abundance) in non-native regions. 3. We used plant–pollinator interaction data from 119 German grassland sites to calculate unbiased indices of plant specialization towards pollinator species and families for 118 European plant species. We related these specialization indices, flowering duration, self-compatibility and their interactions to the degree of invasion of each species in seven large countries on four non-Eurasian continents. 4. In all models, plant species with long flowering durations had the highest degree of invasion. The best model included the specialization index based on pollinator species instead of the one based on pollinator families. Specialization towards pollinator species had a marginally significant positive effect on the degree of invasion in non-native regions for self-compatible, but not for self-incompatible species. 5. Synthesis. We showed that long flowering duration is related to the degree of invasion in other parts of the world, and a trend that pollinator generalization in the native range may interact with self-compatibility in determining the degree of invasion. Therefore, we conclude that such reproductive characteristics should be considered in risk assessment and management of introduced plant species.

Spatiotemporal dynamics: the need for an innovative approach in mountain hazard risk management

Starting with an overview on losses due to mountain hazards in the Russian Federation and the European Alps, the question is raised why a substantial number of events still are recorded—despite considerable efforts in hazard mitigation and risk reduction. The main reason for this paradox lies in a missing dynamic risk-based approach, and it is shown that these dynamics have different roots: firstly, neglecting climate change and systems dynamics, the development of hazard scenarios is based on the static approach of design events. Secondly, due to economic development and population dynamics, the elements at risk exposed are subject to spatial and temporal changes. These issues are discussed with respect to temporal and spatial demands. As a result, it is shown how risk is dynamic on a long-term and short-term scale, which has to be acknowledged in the risk concept if this concept is targeted at a sustainable development of mountain regions. A conceptual model is presented that can be used for dynamical risk assessment, and it is shown by different management strategies how this model may be converted into practice. Furthermore, the interconnectedness and interaction between hazard and risk are addressed in order to enhance prevention, the level of protection and the degree of preparedness.

Assessment of metabolic stability using the rainbow trout (Oncorhynchus mykiss) liver S9 fraction

Standard protocols are given for assessing metabolic stability in rainbow trout using the liver S9 fraction. These protocols describe the isolation of S9 fractions from trout livers, evaluation of metabolic stability using a substrate depletion approach, and expression of the result as in vivo intrinsic clearance. Additional guidance is provided on the care and handling of test animals, design and interpretation of preliminary studies, and development of analytical methods. Although initially developed to predict metabolism impacts on chemical accumulation by fish, these procedures can be used to support a broad range of scientific and risk assessment activities including evaluation of emerging chemical contaminants and improved interpretation of toxicity testing results. These protocols have been designed for rainbow trout and can be adapted to other species as long as species-specific considerations are modified accordingly (e.g., fish maintenance and incubation mixture temperature). Rainbow trout is a cold-water species. Protocols for other species (e.g., carp, a warm-water species) can be developed based on these procedures as long as the specific considerations are taken into account.

Efficiency of risk-based vs . random sampling for the monitoring of tetracycline residues in slaughtered calves in Switzerland

In all European Union countries, chemical residues are required to be routinely monitored in meat. Good farming and veterinary practice can prevent the contamination of meat with pharmaceutical substances, resulting in a low detection of drug residues through random sampling. An alternative approach is to target-monitor farms suspected of treating their animals with antimicrobials. The objective of this project was to assess, using a stochastic model, the efficiency of these two sampling strategies. The model integrated data on Swiss livestock as well as expert opinion and results from studies conducted in Switzerland. Risk-based sampling showed an increase in detection efficiency of up to 100% depending on the prevalence of contaminated herds. Sensitivity analysis of this model showed the importance of the accuracy of prior assumptions for conducting risk-based sampling. The resources gained by changing from random to risk-based sampling should be transferred to improving the quality of prior information.

MiR-205 is progressively down-regulated in lymph node metastasis but fails as a prognostic biomarker in high-risk prostate cancer

The treatment of high-risk prostate cancer (HRPCa) is a tremendous challenge for uro-oncologists. The identification of predictive moleculobiological markers allowing risk assessment of lymph node metastasis and systemic progression is essential in establishing effective treatment. In the current study, we investigate the prognostic potential of miR-205 in HRPCa study and validation cohorts, setting defined clinical endpoints for both. We demonstrate miR-205 to be significantly down-regulated in over 70% of the HRPCa samples analysed and that reconstitution of miR-205 causes inhibition of proliferation and invasiveness in prostate cancer (PCa) cell lines. Additionally, miR-205 is increasingly down-regulated in lymph node metastases compared to the primary tumour indicating that miR-205 plays a role in migration of PCa cells from the original location into extraprostatic tissue. Nevertheless, down-regulation of miR-205 in primary PCa was not correlated to the synchronous presence of metastasis and failed to predict the outcome for HRPCa patients. Moreover, we found a tendency for miR-205 up-regulation to correlate with an adverse outcome of PCa patients suggesting a pivotal role of miR-205 in tumourigenesis. Overall, we showed that miR-205 is involved in the development and metastasis of PCa, but failed to work as a useful clinical biomarker in HRPCa. These findings might have implications for the use of miR-205 as a prognostic or therapeutic target in HRPCa.

A physical approach on flood risk vulnerability of buildings

The design of efficient hydrological risk mitigation strategies and their subsequent implementation relies on a careful vulnerability analysis of the elements exposed. Recently, extensive research efforts were undertaken to develop and refine empirical relationships linking the structural vulnerability of buildings to the impact forces of the hazard processes. These empirical vulnerability functions allow estimating the expected direct losses as a result of the hazard scenario based on spatially explicit representation of the process patterns and the elements at risk classified into defined typological categories. However, due to the underlying empiricism of such vulnerability functions, the physics of the damage-generating mechanisms for a well-defined element at risk with its peculiar geometry and structural characteristics remain unveiled, and, as such, the applicability of the empirical approach for planning hazard-proof residential buildings is limited. Therefore, we propose a conceptual assessment scheme to close this gap. This assessment scheme encompasses distinct analytical steps: modelling (a) the process intensity, (b) the impact on the element at risk exposed and (c) the physical response of the building envelope. Furthermore, these results provide the input data for the subsequent damage evaluation and economic damage valuation. This dynamic assessment supports all relevant planning activities with respect to a minimisation of losses, and can be implemented in the operational risk assessment procedure.

Matrix models for quantifying competitive intransitivity from species abundance data

In a network of competing species, a competitive intransitivity occurs when the ranking of competitive abilities does not follow a linear hierarchy (A > B > C but C > A). A variety of mathematical models suggests that intransitive networks can prevent or slow down competitive exclusion and maintain biodiversity by enhancing species coexistence. However, it has been difficult to assess empirically the relative importance of intransitive competition because a large number of pairwise species competition experiments are needed to construct a competition matrix that is used to parameterize existing models. Here we introduce a statistical framework for evaluating the contribution of intransitivity to community structure using species abundance matrices that are commonly generated from replicated sampling of species assemblages. We provide metrics and analytical methods for using abundance matrices to estimate species competition and patch transition matrices by using reverse-engineering and a colonization-competition model. These matrices provide complementary metrics to estimate the degree of intransitivity in the competition network of the sampled communities. Benchmark tests reveal that the proposed methods could successfully detect intransitive competition networks, even in the absence of direct measures of pairwise competitive strength. To illustrate the approach, we analyzed patterns of abundance and biomass of five species of necrophagous Diptera and eight species of their hymenopteran parasitoids that co-occur in beech forests in Germany. We found evidence for a strong competitive hierarchy within communities of flies and parasitoids. However, for parasitoids, there was a tendency towards increasing intransitivity in higher weight classes, which represented larger resource patches. These tests provide novel methods for empirically estimating the degree of intransitivity in competitive networks from observational datasets. They can be applied to experimental measures of pairwise species interactions, as well as to spatio-temporal samples of assemblages in homogenous environments or environmental gradients.

Von Willebrand Factor Improves Risk Prediction in Addition to N-Terminal Pro-B-type Natriuretic Peptide in Patients Referred to Coronary Angiography and Signs and Symptoms of Heart Failure and Preserved Ejection Fraction.

BACKGROUND Heart failure with preserved ejection fraction (HFpEF) represents a growing health burden associated with substantial mortality and morbidity. Consequently, risk prediction is of highest importance. Endothelial dysfunction has been recently shown to play an important role in the complex pathophysiology of HFpEF. We therefore aimed to assess von Willebrand factor (vWF), a marker of endothelial damage, as potential biomarker for risk assessment in patients with HFpEF. METHODS AND RESULTS Concentrations of vWF were assessed in 457 patients with HFpEF enrolled as part of the LUdwigshafen Risk and Cardiovascular Health (LURIC) study. All-cause mortality was observed in 40% of patients during a median follow-up time of 9.7 years. vWF significantly predicted mortality with a hazard ratio (HR) per increase of 1 SD of 1.45 (95% confidence interval, 1.26-1.68; P<0.001) and remained a significant predictor after adjustment for age, sex, body mass index, N-terminal pro-B-type natriuretic peptide (NT-proBNP), renal function, and frequent HFpEF-related comorbidities (adjusted HR per 1 SD, 1.22; 95% confidence interval, 1.05-1.42; P=0.001). Most notably, vWF showed additional prognostic value beyond that achievable with NT-proBNP indicated by improvements in C-Statistic (vWF×NT-proBNP: 0.65 versus NT-proBNP: 0.63; P for comparison, 0.004) and category-free net reclassification index (37.6%; P<0.001). CONCLUSIONS vWF is an independent predictor of long-term outcome in patients with HFpEF, which is in line with endothelial dysfunction as potential mediator in the pathophysiology of HFpEF. In particular, combined assessment of vWF and NT-proBNP improved risk prediction in this vulnerable group of patients.

gems: An R Package for Simulating from Disease Progression Models

Mathematical models of disease progression predict disease outcomes and are useful epidemiological tools for planners and evaluators of health interventions. The R package gems is a tool that simulates disease progression in patients and predicts the effect of different interventions on patient outcome. Disease progression is represented by a series of events (e.g., diagnosis, treatment and death), displayed in a directed acyclic graph. The vertices correspond to disease states and the directed edges represent events. The package gems allows simulations based on a generalized multistate model that can be described by a directed acyclic graph with continuous transition-specific hazard functions. The user can specify an arbitrary hazard function and its parameters. The model includes parameter uncertainty, does not need to be a Markov model, and may take the history of previous events into account. Applications are not limited to the medical field and extend to other areas where multistate simulation is of interest. We provide a technical explanation of the multistate models used by gems, explain the functions of gems and their arguments, and show a sample application.