Quantifying the utility of taking pills for preventing adverse health outcomes: a cross-sectional survey

ObjectivesThe utility value attributed to taking pills for prevention can have a major effect on the cost-effectiveness of interventions, but few published studies have systematically quantified this value. We sought to quantify the utility value of taking pills used for prevention of cardiovascular disease (CVD).DesignCross-sectional survey.SettingCentral North Carolina.Participants708 healthcare employees aged 18 years and older.Primary and secondary outcomesUtility values for taking 1 pill/day, assessed using time trade-off, modified standard gamble and willingness-to-pay methods.ResultsMean age of respondents was 43 years (19–74). The majority of the respondents were female (83%) and Caucasian (80%). Most (80%) took at least 2 pills/day. Mean utility values for taking 1 pill/day using the time trade-off method were: 0.9972 (95% CI 0.9962 to 0.9980). Values derived from the standard gamble and willingness-to-pay methods were 0.9967 (0.9954 to 0.9979) and 0.9989 (95% CI 0.9986 to 0.9991), respectively. Utility values varied little across characteristics such as age, sex, race, education level or number of pills taken per day.ConclusionsThe utility value of taking pills daily in order to prevent an adverse CVD health outcome is approximately 0.997

Platelets: Functional Biomarkers of Epigenetic Drift

Cardiovascular disease (CVD) risk factors can be classed as modifiable or non-modifiable. Physical inactivity and obesity represent major behavioural risk factors for the initiation, development and progression of CVD. Platelet dysfunction is pivotal to the aetiology of CVD, a chronic vascular inflammatory condition, which is characterised by a lag time between onset and clinical manifestation. This indicates the role of epigenetic drift, defined by stochastic patterns of gene expression not dependent on dynamic changes in coding DNA. The epigenome, a collection of chemical marks on DNA and histones, is established during embryogenesis and modified by age and lifestyle. Biogenesis and effector function of non-coding RNA, such as microRNA, play a regulatory role in gene expression and thus the epigenetic mechanism. In this chapter, we will focus on the effect of the modifiable risk factors of physical activity/inactivity and overweight/obesity on platelet function, via epigenetic changes in both megakaryocytopoiesis and thrombopoiesis. We will also discuss the role of acute exercise on platelet function and the impact of cardiorespiratory fitness (CRF) on platelet responses to acute exercise. This chapter will highlight the potential role of platelets as circulating functional biomarkers of epigenetic drift to implement, optimise and monitor CVD preventive management strategies

Platelets: From Formation to Function

Platelets are small, anucleate cells that travel as resting discoid fragments in the circulation. Their average circulating life span is 8–9 days, and their formation is an elegant and finely orchestrated series of cellular processes known as megakaryocytopoiesis and thrombopoiesis. This involves the commitment of haematopoietic stem cells, proliferation, terminal differentiation of megakaryocytic progenitors and maturation of megakaryocytes to produce functional platelets. This complex process occurs in specialised endosteal and vascular niches in the bone marrow where megakaryocytes form proplatelet projections, releasing platelets into the circulation. Upon contact with an injured blood vessel, they prevent blood loss through processes of adhesion, activation and aggregation. Platelets play a central role in cardiovascular disease (CVD), both in the development of atherosclerosis and as the cellular mediator in the development of thrombosis. Platelets have diverse roles not limited to thrombosis/haemostasis, also being involved in many vascular inflammatory conditions. Depending on the physiological context, platelet functions may be protective or contribute to adverse thrombotic and inflammatory outcomes. In this chapter, we will discuss platelets in context of their formation and function. Because of their multifaceted role in maintaining physiological homeostasis, current and development of platelet function testing platforms will be discussed

Evaluation of machine-learning methods for ligand-based virtual screening

Machine-learning methods can be used for virtual screening by analysing the structural characteristics of molecules of known (in)activity, and we here discuss the use of kernel discrimination and naive Bayesian classifier (NBC) methods for this purpose. We report a kernel method that allows the processing of molecules represented by binary, integer and real-valued descriptors, and show that it is little different in screening performance from a previously described kernel that had been developed specifically for the analysis of binary fingerprint representations of molecular structure. We then evaluate the performance of an NBC when the training-set contains only a very few active molecules. In such cases, a simpler approach based on group fusion would appear to provide superior screening performance, especially when structurally heterogeneous datasets are to be processed

Health equity in the New Zealand health care system: a national survey

<p>Abstract</p> <p>Introduction</p> <p>In all countries people experience different social circumstances that result in avoidable differences in health. In New Zealand, Māori, Pacific peoples, and those with lower socioeconomic status experience higher levels of chronic illness, which is the leading cause of mortality, morbidity and inequitable health outcomes. Whilst the health system can enable a fairer distribution of good health, limited national data is available to measure health equity. Therefore, we sought to find out whether health services in New Zealand were equitable by measuring the level of development of components of chronic care management systems across district health boards. Variation in provision by geography, condition or ethnicity can be interpreted as inequitable.</p> <p>Methods</p> <p>A national survey of district health boards (DHBs) was undertaken on macro approaches to chronic condition management with detail on cardiovascular disease, chronic obstructive pulmonary disease, congestive heart failure, stroke and diabetes. Additional data from expert informant interviews on program reach and the cultural needs of Māori and Pacific peoples was sought. Survey data were analyzed on dimensions of health equity relevant to strategic planning and program delivery. Results are presented as descriptive statistics and free text. Interviews were transcribed and NVivo 8 software supported a general inductive approach to identify common themes.</p> <p>Results</p> <p>Survey responses were received from the majority of DHBs (15/21), some PHOs (21/84) and 31 expert informants. Measuring, monitoring and targeting equity is not systematically undertaken. The Health Equity Assessment Tool is used in strategic planning but not in decisions about implementing or monitoring disease programs. Variable implementation of evidence-based practices in disease management and multiple funding streams made program implementation difficult. Equity for Māori is embedded in policy, this is not so for other ethnic groups or by geography. Populations that conventional practitioners find hard to reach, despite recognized needs, are often underserved. Nurses and community health workers carried a disproportionate burden of care. Cultural and diversity training is not a condition of employment.</p> <p>Conclusions</p> <p>There is a struggle to put equity principles into practice, indicating will without enactment. Equity is not addressed systematically below strategic levels and equity does not shape funding decisions, program development, implementation and monitoring. Equity is not incentivized although examples of exceptional practice, driven by individuals, are evident across New Zealand.</p

PCR versus Hybridization for Detecting Virulence Genes of Enterohemorrhagic Escherichia coli

We compared PCR amplification of 9 enterohemorrhagic Escherichia coli virulence factors among 40 isolates (21 O/H antigenicity classes) with DNA hybridization. Both methods showed 100% of the chromosomal and phage genes: eae, stx, and stx2. PCR did not detect 4%–20% of hybridizable plasmid genes: hlyA, katP, espP, toxB, open reading frame (ORF) 1, and ORF2

Changes in inferior vena cava area represent a more sensitive metric than changes in filling pressures during experimental manipulation of intravascular volume and tone

AIMS: Remote monitoring of pulmonary artery pressure has reduced heart failure (HF) hospitalizations in chronic HF as elevation of pulmonary artery pressure provides information that can guide treatment. The venous system is characterized by high capacitance, thus substantial increases in intravascular volume can occur before filling pressures increase. The inferior vena cava (IVC) is a highly compliant venous conduit and thus a candidate for early detection of change in intravascular volume. We aimed to compare IVC cross-sectional area using a novel sensor with cardiac filling pressures during experimental manipulation of volume status, vascular tone, and cardiac function. METHODS AND RESULTS: Experiments were conducted in sheep to manipulate volume status (colloid infusion), vascular tone (nitroglycerin infusion) and cardiac function (rapid cardiac pacing). A wireless implantable IVC sensor was validated ex-vivo and in-vivo, and then used to measure the cross-sectional area of the IVC. Right- and left-sided cardiac filling pressures were obtained via right heart catheterization. The IVC sensor provided highly accurate and precise measurements of cross-sectional area in ex-vivo and in-vivo validation. IVC area changes were more sensitive than the corresponding changes in cardiac filling pressures during colloid infusion (p < 0.001), vasodilatation (p < 0.001) and cardiac dysfunction induced by rapid pacing (p ≤ 0.02). CONCLUSIONS: Inferior vena cava area can be remotely and accurately measured in real time with a wireless implantable sensor. Changes in IVC area are more sensitive than corresponding changes in filling pressures following experimental volume loading and fluid redistribution. Additional research is warranted to understand if remote monitoring of the IVC may have advantages over pressure-based monitors in HF

The <i>Castalia</i> mission to Main Belt Comet 133P/Elst-Pizarro

We describe Castalia, a proposed mission to rendezvous with a Main Belt Comet (MBC), 133P/Elst-Pizarro. MBCs are a recently discovered population of apparently icy bodies within the main asteroid belt between Mars and Jupiter, which may represent the remnants of the population which supplied the early Earth with water. Castalia will perform the first exploration of this population by characterising 133P in detail, solving the puzzle of the MBC’s activity, and making the first in situ measurements of water in the asteroid belt. In many ways a successor to ESA’s highly successful Rosetta mission, Castalia will allow direct comparison between very different classes of comet, including measuring critical isotope ratios, plasma and dust properties. It will also feature the first radar system to visit a minor body, mapping the ice in the interior. Castalia was proposed, in slightly different versions, to the ESA M4 and M5 calls within the Cosmic Vision programme. We describe the science motivation for the mission, the measurements required to achieve the scientific goals, and the proposed instrument payload and spacecraft to achieve these

Autoimmune and autoinflammatory mechanisms in uveitis

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts