Using pharmacy dispensing data to predict falls in older individuals

Aims Associations between individual medication use and falling in older individuals are well-documented. However, a comprehensive risk score that takes into account overall medication use and that can be used in daily pharmacy practice is lacking. We, therefore, aimed to determine whether pharmacy dispensing records can be used to predict falls. Methods A retrospective cohort study was conducted using pharmacy dispensing data and self-reported falls among 3454 Dutch individuals aged >= 65 years. Two different methods were used to classify medication exposure for each person: the drug burden index (DBI) for cumulative anticholinergic and sedative medication exposure as well as exposure to fall risk-increasing drugs (FRIDs). Multinomial regression analyses, adjusted for age and sex, were conducted to investigate the association between medication exposure and falling classified as nonfalling, single falling and recurrent falling. The predictive performances of the DBI and FRIDs exposure were estimated by the polytomous discrimination index (PDI). Results There were 521 single fallers (15%) and 485 recurrent fallers (14%). We found significant associations between a DBI >= 1 and single falling (adjusted odds ratio: 1.30 [95% confidence interval {CI}: 1.02-1.66]) and recurrent falling (adjusted odds ratio: 1.60 [95%CI: 1.25-2.04]). The PDI of the DBI model was 0.41 (95%CI: 0.39-0.42) and the PDI of the FRIDs model was 0.45 (95%CI: 0.43-0.47), indicating poor discrimination between fallers and nonfallers. Conclusion The study shows significant associations between medication use and falling. However, the medication-based models were insufficient and other factors should be included to develop a risk score for pharmacy practice

Spiral dynamics in the management of sustainable development of society

The article discusses issues related to the implementation of the concept of sustainable development through the prism of the spiral dynamics approach. An example of sustainable models for the implementation of activities in the forestry area and considered inconsistencies in conceptual attitudes necessary to implement such an approach and in the vMems of today. The purpose of this study is consideration of the applied aspects management on the value-based change. As part of the study, an information and management scheme for the forestry industry has been developed, which allows you to see information in the process relationships. General recommendations for the management of values have been developed on a specific example of the forestry industry. Modern society requires specialists of a new formation, able to integrate spiral movements, ready to design new businesses and projects, taking into account the requirements of the 2nd level vMems

Spatial mapping of the collagen distribution in human and mouse tissues by force volume atomic force microscopy

Changes in the elastic properties of living tissues during normal development and in pathological processes are often due to modifications of the collagen component of the extracellular matrix at various length scales. Force volume AFM can precisely capture the mechanical properties of biological samples with force sensitivity and spatial resolution. The integration of AFM data with data of the molecular composition contributes to understanding the interplay between tissue biochemistry, organization and function. The detection of micrometer-size, heterogeneous domains at different elastic moduli in tissue sections by AFM has remained elusive so far, due to the lack of correlations with histological, optical and biochemical assessments. In this work, force volume AFM is used to identify collagen-enriched domains, naturally present in human and mouse tissues, by their elastic modulus. Collagen identification is obtained in a robust way and affordable timescales, through an optimal design of the sample preparation method and AFM parameters for faster scan with micrometer resolution. The choice of a separate reference sample stained for collagen allows correlating elastic modulus with collagen amount and position with high statistical significance. The proposed preparation method ensures safe handling of the tissue sections guarantees the preservation of their micromechanical characteristics over time and makes it much easier to perform correlation experiments with different biomarkers independently

Deconvoluting hepatic processing of carbon nanotubes

Single-wall carbon nanotubes present unique opportunities for drug delivery, but have not advanced into the clinic. Differential nanotube accretion and clearance from critical organs have been observed, but the mechanism not fully elucidated. The liver has a complex cellular composition that regulates a range of metabolic functions and coincidently accumulates most particulate drugs. Here we provide the unexpected details of hepatic processing of covalently functionalized nanotubes including receptor-mediated endocytosis, cellular trafficking and biliary elimination. Ammonium-functionalized fibrillar nanocarbon is found to preferentially localize in the fenestrated sinusoidal endothelium of the liver but not resident macrophages. Stabilin receptors mediate the endocytic clearance of nanotubes. Biocompatibility is evidenced by the absence of cell death and no immune cell infiltration. Towards clinical application of this platform, nanotubes were evaluated for the first time in non-human primates. The pharmacologic profile in cynomolgus monkeys is equivalent to what was reported in mice and suggests that nanotubes should behave similarly in humans

Improving 10-year cardiovascular risk prediction in apparently healthy people : flexible addition of risk modifiers on top of SCORE2

AIMS: In clinical practice, factors associated with cardiovascular disease (CVD) like albuminuria, education level, or coronary artery calcium (CAC) are often known, but not incorporated in cardiovascular risk prediction models. The aims of the current study were to evaluate a methodology for the flexible addition of risk modifying characteristics on top of SCORE2 and to quantify the added value of several clinically relevant risk modifying characteristics. METHODS AND RESULTS: Individuals without previous CVD or DM were included from the UK Biobank; Atherosclerosis Risk in Communities (ARIC); Multi-Ethnic Study of Atherosclerosis (MESA); European Prospective Investigation into Cancer, The Netherlands (EPIC-NL); and Heinz Nixdorf Recall (HNR) studies (n = 409 757) in whom 16 166 CVD events and 19 149 non-cardiovascular deaths were observed over exactly 10.0 years of follow-up. The effect of each possible risk modifying characteristic was derived using competing risk-adjusted Fine and Gray models. The risk modifying characteristics were applied to individual predictions with a flexible method using the population prevalence and the subdistribution hazard ratio (SHR) of the relevant predictor. Risk modifying characteristics that increased discrimination most were CAC percentile with 0.0198 [95% confidence interval (CI) 0.0115; 0.0281] and hs-Troponin-T with 0.0100 (95% CI 0.0063; 0.0137). External validation was performed in the Clinical Practice Research Datalink (CPRD) cohort (UK, n = 518 015, 12 675 CVD events). Adjustment of SCORE2-predicted risks with both single and multiple risk modifiers did not negatively affect calibration and led to a modest increase in discrimination [0.740 (95% CI 0.736-0.745) vs. unimproved SCORE2 risk C-index 0.737 (95% CI 0.732-0.741)]. CONCLUSION: The current paper presents a method on how to integrate possible risk modifying characteristics that are not included in existing CVD risk models for the prediction of CVD event risk in apparently healthy people. This flexible methodology improves the accuracy of predicted risks and increases applicability of prediction models for individuals with additional risk known modifiers

Determinants of Gammaherpesvirus Shedding in Saliva Among Ugandan Children and Their Mothers.

Background: Epstein-Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV) are transmitted via saliva, but factors associated with salivary shedding are unknown. Methods: We measured the DNA load of both viruses in saliva specimens collected from approximately 500 Ugandan mothers and their 6-year-old children, testing all participants for EBV and KSHV-seropositive individuals for KSHV. Results: EBV and KSHV were shed by 72% and 22% of mothers, respectively, and by 85% and 40% of children, respectively; boys were more likely than girls to shed KSHV (48% vs 30%) but were equally likely to shed EBV. Children shed more KSHV and EBV than mothers, but salivary loads of EBV and KSHV were similar. KSHV shedding increased with increasing anti-KSHV (K8.1) antibodies in mothers and with decreasing antimalarial antibodies both in mothers and children. Among mothers, 40% of KSHV shedders also shed EBV, compared with 75% of KSHV nonshedders; among children, EBV was shed by 65% and 83%, respectively. Conclusions: In summary, in this population, individuals were more likely to shed EBV than KSHV in saliva. We identified several factors, including child's sex, that influence KSHV shedding, and we detected an inverse relationship between EBV and KSHV shedding, suggesting a direct or indirect interaction between the two viruses

Tunneling Nanotubes Provide a Unique Conduit for Intercellular Transfer of Cellular Contents in Human Malignant Pleural Mesothelioma

Tunneling nanotubes are long, non-adherent F-actin-based cytoplasmic extensions which connect proximal or distant cells and facilitate intercellular transfer. The identification of nanotubes has been limited to cell lines, and their role in cancer remains unclear. We detected tunneling nanotubes in mesothelioma cell lines and primary human mesothelioma cells. Using a low serum, hyperglycemic, acidic growth medium, we stimulated nanotube formation and bidirectional transfer of vesicles, proteins, and mitochondria between cells. Notably, nanotubes developed between malignant cells or between normal mesothelial cells, but not between malignant and normal cells. Immunofluorescent staining revealed their actin-based assembly and structure. Metformin and an mTor inhibitor, Everolimus, effectively suppressed nanotube formation. Confocal microscopy with 3-dimensional reconstructions of sectioned surgical specimens demonstrated for the first time the presence of nanotubes in human mesothelioma and lung adenocarcinoma tumor specimens. We provide the first evidence of tunneling nanotubes in human primary tumors and cancer cells and propose that these structures play an important role in cancer cell pathogenesis and invasion

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

Evidence synthesis to inform model-based cost-effectiveness evaluations of diagnostic tests: a methodological systematic review of health technology assessments

Background: Evaluations of diagnostic tests are challenging because of the indirect nature of their impact on patient outcomes. Model-based health economic evaluations of tests allow different types of evidence from various sources to be incorporated and enable cost-effectiveness estimates to be made beyond the duration of available study data. To parameterize a health-economic model fully, all the ways a test impacts on patient health must be quantified, including but not limited to diagnostic test accuracy. Methods: We assessed all UK NIHR HTA reports published May 2009-July 2015. Reports were included if they evaluated a diagnostic test, included a model-based health economic evaluation and included a systematic review and meta-analysis of test accuracy. From each eligible report we extracted information on the following topics: 1) what evidence aside from test accuracy was searched for and synthesised, 2) which methods were used to synthesise test accuracy evidence and how did the results inform the economic model, 3) how/whether threshold effects were explored, 4) how the potential dependency between multiple tests in a pathway was accounted for, and 5) for evaluations of tests targeted at the primary care setting, how evidence from differing healthcare settings was incorporated. Results: The bivariate or HSROC model was implemented in 20/22 reports that met all inclusion criteria. Test accuracy data for health economic modelling was obtained from meta-analyses completely in four reports, partially in fourteen reports and not at all in four reports. Only 2/7 reports that used a quantitative test gave clear threshold recommendations. All 22 reports explored the effect of uncertainty in accuracy parameters but most of those that used multiple tests did not allow for dependence between test results. 7/22 tests were potentially suitable for primary care but the majority found limited evidence on test accuracy in primary care settings. Conclusions: The uptake of appropriate meta-analysis methods for synthesising evidence on diagnostic test accuracy in UK NIHR HTAs has improved in recent years. Future research should focus on other evidence requirements for cost-effectiveness assessment, threshold effects for quantitative tests and the impact of multiple diagnostic tests