Prospects for research in haemophilia with real-world data-An analysis of German registry and secondary data.

INTRODUCTION AND AIM: Open questions in haemophilia, such as effectiveness of innovative therapies, clinical and patient-reported outcomes (PROs), epidemiology and cost, await answers. The aim was to identify data attributes required and investigate the availability, appropriateness and accessibility of real-world data (RWD) from German registries and secondary databases to answer the aforementioned questions. METHODS: Systematic searches were conducted in BIOSIS, EMBASE and MEDLINE to identify non-commercial secondary healthcare databases and registries of patients with haemophilia (PWH). Inclusion of German patients, type of patients, data elements-stratified by use in epidemiology, safety, outcomes and health economics research-and accessibility were investigated by desk research. RESULTS: Screening of 676 hits, identification of four registries [national PWH (DHR), national/international paediatric (GEPARD, PEDNET), international safety monitoring (EUHASS)] and seven national secondary databases. Access was limited to participants in three registries and to employees in one secondary database. One registry asks for PROs. Limitations of secondary databases originate from the ICD-coding system (missing: severity of haemophilia, presence of inhibitory antibodies), data protection laws and need to monitor reliability. CONCLUSION: Rigorous observational analysis of German haemophilia RWD shows that there is potential to supplement current knowledge and begin to address selected policy goals. To improve the value of existing RWD, the following efforts are proposed: ethical, legal and methodological discussions on data linkage across different sources, formulation of transparent governance rules for data access, redefinition of the ICD-coding, standardized collection of outcome data and implementation of incentives for treatment centres to improve data collection.

Using a Bayesian network to clarify areas requiring research in a host-pathogen system.

Bayesian network analyses can be used to interactively change the strength of effect of variables in a model to explore complex relationships in new ways. In doing so, they allow one to identify influential nodes that are not well studied empirically so that future research can be prioritized. We identified relationships in host and pathogen biology to examine disease-driven declines of amphibians associated with amphibian chytrid fungus (Batrachochytrium dendrobatidis). We constructed a Bayesian network consisting of behavioral, genetic, physiological, and environmental variables that influence disease and used them to predict host population trends. We varied the impacts of specific variables in the model to reveal factors with the most influence on host population trend. The behavior of the nodes (the way in which the variables probabilistically responded to changes in states of the parents, which are the nodes or variables that directly influenced them in the graphical model) was consistent with published results. The frog population had a 49% probability of decline when all states were set at their original values, and this probability increased when body temperatures were cold, the immune system was not suppressing infection, and the ambient environment was conducive to growth of B. dendrobatidis. These findings suggest the construction of our model reflected the complex relationships characteristic of host-pathogen interactions. Changes to climatic variables alone did not strongly influence the probability of population decline, which suggests that climate interacts with other factors such as the capacity of the frog immune system to suppress disease. Changes to the adaptive immune system and disease reservoirs had a large effect on the population trend, but there was little empirical information available for model construction. Our model inputs can be used as a base to examine other systems, and our results show that such analyses are useful tools for reviewing existing literature, identifying links poorly supported by evidence, and understanding complexities in emerging infectious-disease systems.

Correction: The nanotipped hairs of gecko skin and biotemplated replicas impair and/or kill pathogenic bacteria with high efficiency.

Correction for 'The nanotipped hairs of gecko skin and biotemplated replicas impair and/or kill pathogenic bacteria with high efficiency' by X. Li, et al., Nanoscale, 2016, 8, 18860-18869.

The nanotipped hairs of gecko skin and biotemplated replicas impair and/or kill pathogenic bacteria with high efficiency.

We show that gecko microspinules (hairs) and their equivalent replicas, bearing nanoscale tips, can kill or impair surface associating oral pathogenic bacteria with high efficiency even after 7 days of repeated attacks. Scanning Electron Microscopy suggests that there is more than one mechanism contributing to cell death which appears to be related to the scaling of the bacteria type with the hair arrays and accessibility to the underlying nano-topography of the hierarchical surfaces.

[Discretionary decisions in claims data analyses and their effects - an explorative comparison using the example of a cost of illness study on dementia]. / Methodische Ermessensspielräume bei der Sekundärdatenanalyse von GKV-Daten und ihre Auswirkungen - explorative Darstellung am Beispiel einer Kostenstudie zu Demenz.

Claims data-based studies provide insight into the delivery of health care services within the statutory health insurance (SHI) system. So far discretionary decisions concerning the definition of service utilization are seldom discussed. Using claims data of 9 147 dementia patients insured with AOK Bavaria SHI fund as an example, this paper compares different definitions of service utilisation and the corresponding costs of care. In total, the different approaches do not always result in different figures. Indeed the observed variation depends on the relative frequency of equivocally interpretable services within the study sample. Based on these results it is possible to provide recommendations for future standards for claims data analyses.

Evaluation of offspring size-number invariants in 12 species of lizard.

The optimal division of resources into offspring size vs. number is one of the classic problems in life-history evolution. Importantly, models that take into account the discrete nature of resource division at low clutch sizes suggest that the variance in offspring size should decline with increasing clutch size according to an invariant relationship. We tested this prediction in 12 species of lizard with small clutch sizes. Contrary to expectations, not all species showed a negative relationship between variance in offspring size and clutch size, and the pattern significantly deviated from quantitative predictions in five of the 12 species. We suggest that the main limitation of current size-number models for small clutch sizes is that they rely on assumptions of hierarchical allocation strategies with independence between allocation decisions. Indeed, selection may favour alternative mechanisms of reproductive allocation that avoid suboptimal allocation imposed by the indivisible fraction at low clutch sizes.

Does total reproductive effort evolve independently of offspring size?

In all species, patterns of reproductive allocation have important fitness consequences and therefore important implications for life-history evolution. Nearly universally, theory in this field has modeled as independent the evolution of total allocation to offspring and the subsequent division of this allocation into many small versus few large offspring. Yet, some theory and a very small amount of experimental evidence suggest that these life-history traits may be evolutionarily linked. Using comparative analyses of copepod life histories, we illustrate that rather than being evolutionarily independent these traits can be linked, in this case, across a very large clade of invertebrates. Our results indicate that a more complete understanding of the evolution of these traits will require greater consideration of simultaneous allocation decisions, rather than sequential ones, and other genetic and selective mechanisms.

Failure of strange females to cause pregnancy block in collared lemmings, Dicrostonyx groenlandicus.

The effects of exposure to unfamiliar females on pregnancy success of recently mated females were examined in collared lemmings (Dicrostonyx groenlandicus). Four days after mating, females in their home cage were exposed to strange, female intruders that were either nonpregnant or 16 days pregnant. Other recently mated females were introduced to the home cage of 16-day-pregnant females. Pregnancy success of the recently mated females was not reduced in any of these treatments. In the paired encounters, there was no relationship between dominance status and pregnancy status, nor between dominance and pregnancy success. These results do not support the hypothesis that in species in which females are aggressive and readily commit infanticide, unfamiliar females should cause other females to terminate early-stage pregnancies.

Factors affecting incidence of infanticide and discrimination of related and unrelated neonates in male Mus musculus.

Infanticide by males was examined in two strains (C57B1 and DBA) of the house mouse (Mus musculus). Males that had contact with a female within the previous 2-3 weeks rarely committed infanticide when introduced to the home cage of a female and her 1-day-old neonates, even when the female and neonates were of a different strain and from a different colony. In contrast, 90% of C57B1 males that had no contact with a female for more than 7 weeks killed pups when placed in the female's home cage, and 60% killed when a 1-day-old pup was introduced to the male's home cage. No difference in levels of infanticide occurred when grouped males were compared to isolated males. These results indicate that infanticide is not dependent upon recognition of the pups or the female, but depends on the male's previous exposure to females. Infanticidal behavior is not directly determined by genetic relationship, but the factors that inhibit this behavior reduce the probability that a male will kill his own offspring.