Assessing airway inflammation in clinical practice – experience with spontaneous sputum analysis

<p>Abstract</p> <p>Background</p> <p>The assessment of airway inflammation for the diagnosis of asthma or COPD is still uncommon in pneumology-specialized general practices. In this respect, the measurement of exhaled nitric oxide (NO), as a fast and simple methodology, is increasingly used. The indirect assessment of airway inflammation, however, does have its limits and therefore there will always be a need for methods enabling a direct evaluation of airway inflammatory cell composition. Sampling of spontaneous sputum is a well-known, simple, economic and non-invasive method to derive a qualitative cytology of airway cells and here we aimed to assess today's value of spontaneous sputum cytology in clinical practice.</p> <p>Methods</p> <p>Three pneumologists provided final diagnoses in 481 patients having sputum cytology and we retrospectively determined posterior versus prior probabilities of inflammatory airway disorders. Moreover, in a prospective part comprising 108 patients, pneumologists rated their confidence in a given diagnosis before and after knowing sputum cytology and rated its impact on the diagnostic process on an analogue scale.</p> <p>Results</p> <p>Among the 481 patients, 45% were diagnosed as having asthma and/or airway hyperresponsiveness. If patients showed sputum eosinophilia, the prevalence of this diagnosis was elevated to 73% (n = 109, p < 0.001). The diagnosis of COPD increased from 40 to 66% in patients with neutrophilia (n = 29, p < 0.01).</p> <p>Thirty-three of the 108 patients were excluded from the prospective part (26 insufficient samples, 7 incomplete questionnaires). In 48/75 cases the confidence into a diagnosis was raised after knowing sputum cytology, and in 15/75 cases the diagnosis was changed as cytology provided new clues.</p> <p>Conclusion</p> <p>Our data suggest that spontaneous sputum cytology is capable of assisting in the diagnosis of inflammatory airway diseases in the outpatient setting. Despite the limitations by the semiquantitative assessment and lower sputum quality, the supportive power and the low economic effort needed can justify the use of this method, particularly if the diagnosis in question is thought to have an allergic background.</p

Assessment of Left Ventricular Geometrical Patterns and Function among Hypertensive Patients at a Tertiary Hospital, Northern Tanzania.

With hypertension, the cardiovascular system changes to adapt to the varying neuro-humoral and hemodynamic changes and this may lead to the development of different left ventricular geometric patterns, each carrying a different risk profile for major adverse cardiovascular events. Using a consecutive sampling technique, a cross-sectional, prospective, hospital based study was done and two hundred and twenty seven (227) hypertensive patients were studied. The distribution of different abnormal LV geometrical patterns was 19.8%, 28.2%, 22% for concentric remodelling, concentric hypertrophy and eccentric hypertrophy respectively. With echocardiographic criteria, the proportion of patients with left ventricular hypertrophy (LVH) was higher when left ventricular mass (LVM) was indexed to height(2.7) than to body surface area (70.0% vs. 52.9%). Duration of hypertension markedly influenced the type of LV geometry with normal LV geometry predominating in early hypertension and abnormal geometrical patterns predominating in late hypertension. The left ventricular fractional shortening decreased with duration of hypertension and was common in patients with eccentric hypertrophy. Age of the patient, systolic blood pressure, duration of hypertension and body mass index were found to be independent predictors left ventricular hypertrophy. About 70% of hypertensive patients had abnormal geometry existing in different patterns. Eccentric hypertrophy had more of clinical and echocardiographic features suggestive of reduced left ventricular systolic function. Hypertensive patients should be recognized as a heterogeneous population and therefore stratifying them into their respective LV geometrical patterns is useful as way of assessing their risk profile as well as instituting appropriate management

A Geographically-Restricted but Prevalent Mycobacterium tuberculosis Strain Identified in the West Midlands Region of the UK between 1995 and 2008

Background: We describe the identification of, and risk factors for, the single most prevalent Mycobacterium tuberculosis strain in the West Midlands region of the UK.Methodology/Principal Findings: Prospective 15-locus MIRU-VNTR genotyping of all M. tuberculosis isolates in the West Midlands between 2004 and 2008 was undertaken. Two retrospective epidemiological investigations were also undertaken using univariable and multivariable logistic regression analysis. The first study of all TB patients in the West Midlands between 2004 and 2008 identified a single prevalent strain in each of the study years (total 155/3,056 (5%) isolates). This prevalent MIRU-VNTR profile (32333 2432515314 434443183) remained clustered after typing with an additional 9-loci MIRU-VNTR and spoligotyping. The majority of these patients (122/155, 79%) resided in three major cities located within a 40 km radius. From the apparent geographical restriction, we have named this the "Mercian" strain. A multivariate analysis of all TB patients in the West Midlands identified that infection with a Mercian strain was significantly associated with being UK-born (OR = 9.03, 95% CI = 4.56-17.87, p 65 years old (OR = 0.25, 95% CI = 0.09-0.67, p < 0.01). A second more detailed investigation analyzed a cohort of 82 patients resident in Wolverhampton between 2003 and 2006. A significant association with being born in the UK remained after a multivariate analysis (OR = 9.68, 95% CI = 2.00-46.78, p < 0.01) and excess alcohol intake and cannabis use (OR = 6.26, 95% CI = 1.45-27.02, p = .01) were observed as social risk factors for infection.Conclusions/Significance: The continued consistent presence of the Mercian strain suggests ongoing community transmission. Whilst significant associations have been found, there may be other common risk factors yet to be identified. Future investigations should focus on targeting the relevant risk groups and elucidating the biological factors that mediate continued transmission of this strain

One million dog vaccinations recorded on mHealth innovation used to direct teams in numerous rabies control campaigns

<div><p>Background</p><p>Canine transmitted rabies kills an estimated 59,000 people annually, despite proven methods for elimination through mass dog vaccination. Challenges in directing and monitoring numerous remote vaccination teams across large geographic areas remain a significant barrier to the up-scaling of focal vaccination programmes to sub-national and national level. Smartphone technology (mHealth) is increasingly being used to enhance the coordination and efficiency of public health initiatives in developing countries, however examples of successful scaling beyond pilot implementation are rare. This study describes a smartphone app and website platform, “Mission Rabies App”, used to co-ordinate rabies control activities at project sites in four continents to vaccinate over one million dogs.</p><p>Methods</p><p>Mission Rabies App made it possible to not only gather relevant campaign data from the field, but also to direct vaccination teams systematically in near real-time. The display of user-allocated boundaries on Google maps within data collection forms enabled a project manager to define each team’s region of work, assess their output and assign subsequent areas to progressively vaccinate across a geographic area. This ability to monitor work and react to a rapidly changing situation has the potential to improve efficiency and coverage achieved, compared to regular project management structures, as well as enhancing capacity for data review and analysis from remote areas. The ability to plot the location of every vaccine administered facilitated engagement with stakeholders through transparent reporting, and has the potential to motivate politicians to support such activities.</p><p>Results</p><p>Since the system launched in September 2014, over 1.5 million data entries have been made to record dog vaccinations, rabies education classes and field surveys in 16 countries. Use of the system has increased year-on-year with adoption for mass dog vaccination campaigns at the India state level in Goa and national level in Haiti.</p><p>Conclusions</p><p>Innovative approaches to rapidly scale mass dog vaccination programmes in a sustained and systematic fashion are urgently needed to achieve the WHO, OIE and FAO goal to eliminate canine-transmitted human deaths by 2030. The Mission Rabies App is an mHealth innovation which greatly reduces the logistical and managerial barriers to implementing large scale rabies control activities. Free access to the platform aims to support pilot campaigns to better structure and report on proof-of-concept initiatives, clearly presenting outcomes and opportunities for expansion. The functionalities of the Mission Rabies App may also be beneficial to other infectious disease interventions.</p></div

Kinetic modelling of competition and depletion of shared miRNAs by competing endogenous RNAs

Non-conding RNAs play a key role in the post-transcriptional regulation of mRNA translation and turnover in eukaryotes. miRNAs, in particular, interact with their target RNAs through protein-mediated, sequence-specific binding, giving rise to extended and highly heterogeneous miRNA-RNA interaction networks. Within such networks, competition to bind miRNAs can generate an effective positive coupling between their targets. Competing endogenous RNAs (ceRNAs) can in turn regulate each other through miRNA-mediated crosstalk. Albeit potentially weak, ceRNA interactions can occur both dynamically, affecting e.g. the regulatory clock, and at stationarity, in which case ceRNA networks as a whole can be implicated in the composition of the cell's proteome. Many features of ceRNA interactions, including the conditions under which they become significant, can be unraveled by mathematical and in silico models. We review the understanding of the ceRNA effect obtained within such frameworks, focusing on the methods employed to quantify it, its role in the processing of gene expression noise, and how network topology can determine its reach.Comment: review article, 29 pages, 7 figure

Developing an Individual-level Geodemographic Classification

Geodemographics is a spatially explicit classification of socio-economic data, which can be used to describe and analyse individuals by where they live. Geodemographic information is used by the public sector for planning and resource allocation but it also has considerable use within commercial sector applications. Early geodemographic systems, such as the UK’s ACORN (A Classification of Residential Neighbourhoods), used only area-based census data, but more recent systems have added supplementary layers of information, e.g. credit details and survey data, to provide better discrimination between classes. Although much more data has now become available, geodemographic systems are still fundamentally built from area-based census information. This is partly because privacy laws require release of census data at an aggregate level but mostly because much of the research remains proprietary. Household level classifications do exist but they are often based on regressions between area and household data sets. This paper presents a different approach for creating a geodemographic classification at the individual level using only census data. A generic framework is presented, which classifies data from the UK Census Small Area Microdata and then allocates the resulting clusters to a synthetic population created via microsimulation. The framework is then applied to the creation of an individual-based system for the city of Leeds, demonstrated using data from the 2001 census, and is further validated using individual and household survey data from the British Household Panel Survey

Cross-modal visuo-haptic mental rotation: comparing objects between senses

The simple experience of a coherent percept while looking and touching an object conceals an intriguing issue: different senses encode and compare information in different modality-specific reference frames. We addressed this problem in a cross-modal visuo-haptic mental rotation task. Two objects in various orientations were presented at the same spatial location, one visually and one haptically. Participants had to identify the objects as same or different. The relative angle between viewing direction and hand orientation was manipulated (Aligned versus Orthogonal). In an additional condition (Delay), a temporal delay was introduced between haptic and visual explorations while the viewing direction and the hand orientation were orthogonal to each other. Whereas the phase shift of the response time function was close to 0° in the Aligned condition, we observed a consistent phase shift in the hand’s direction in the Orthogonal condition. A phase shift, although reduced, was also found in the Delay condition. Counterintuitively, these results mean that seen and touched objects do not need to be physically aligned for optimal performance to occur. The present results suggest that the information about an object is acquired in separate visual and hand-centered reference frames, which directly influence each other and which combine in a time-dependent manner

Expression of Distal-less, dachshund, and optomotor blind in Neanthes arenaceodentata (Annelida, Nereididae) does not support homology of appendage-forming mechanisms across the Bilateria

The similarity in the genetic regulation of arthropod and vertebrate appendage formation has been interpreted as the product of a plesiomorphic gene network that was primitively involved in bilaterian appendage development and co-opted to build appendages (in modern phyla) that are not historically related as structures. Data from lophotrochozoans are needed to clarify the pervasiveness of plesiomorphic appendage forming mechanisms. We assayed the expression of three arthropod and vertebrate limb gene orthologs, Distal-less (Dll), dachshund (dac), and optomotor blind (omb), in direct-developing juveniles of the polychaete Neanthes arenaceodentata. Parapodial Dll expression marks premorphogenetic notopodia and neuropodia, becoming restricted to the bases of notopodial cirri and to ventral portions of neuropodia. In outgrowing cephalic appendages, Dll activity is primarily restricted to proximal domains. Dll expression is also prominent in the brain. dac expression occurs in the brain, nerve cord ganglia, a pair of pharyngeal ganglia, presumed interneurons linking a pair of segmental nerves, and in newly differentiating mesoderm. Domains of omb expression include the brain, nerve cord ganglia, one pair of anterior cirri, presumed precursors of dorsal musculature, and the same pharyngeal ganglia and presumed interneurons that express dac. Contrary to their roles in outgrowing arthropod and vertebrate appendages, Dll, dac, and omb lack comparable expression in Neanthes appendages, implying independent evolution of annelid appendage development. We infer that parapodia and arthropodia are not structurally or mechanistically homologous (but their primordia might be), that Dll’s ancestral bilaterian function was in sensory and central nervous system differentiation, and that locomotory appendages possibly evolved from sensory outgrowths

Using the net benefit regression framework to construct cost-effectiveness acceptability curves: an example using data from a trial of external loop recorders versus Holter monitoring for ambulatory monitoring of "community acquired" syncope

BACKGROUND: Cost-effectiveness acceptability curves (CEACs) describe the probability that a new treatment or intervention is cost-effective. The net benefit regression framework (NBRF) allows cost-effectiveness analysis to be done in a simple regression framework. The objective of the paper is to illustrate how net benefit regression can be used to construct a CEAC. METHODS: One hundred patients referred for ambulatory monitoring with syncope or presyncope were randomized to a one-month external loop recorder (n = 49) or 48-hour Holter monitor (n = 51). The primary endpoint was symptom-rhythm correlation during monitoring. Direct costs were calculated based on the 2003 Ontario Health Insurance Plan (OHIP) fee schedule combined with hospital case costing of labour, materials, service and overhead costs for diagnostic testing and related equipment. RESULTS: In the loop recorder group, 63.27% of patients (31/49) had symptom recurrence and successful activation, compared to 23.53% in the Holter group (12/51). The cost in US dollars for loop recording was $648.50 and$212.92 for Holter monitoring. The incremental cost-effectiveness ratio (ICER) of the loop recorder was $1,096 per extra successful diagnosis. The probability that the loop recorder was cost-effective compared to the Holter monitor was estimated using net benefit regression and plotted on a CEAC. In a sensitivity analysis, bootstrapping was used to examine the effect of distributional assumptions. CONCLUSION: The NBRF is straightforward to use and interpret. The resulting uncertainty surrounding the regression coefficient relates to the CEAC. When the link from the regression's p-value to the probability of cost-effectiveness is tentative, bootstrapping may be used

Models of Temporal Enhanced Ultrasound Data for Prostate Cancer Diagnosis: The Impact of Time-Series Order

Recent studies have shown the value of Temporal Enhanced Ultrasound (TeUS) imaging for tissue characterization in transrectal ultrasound-guided prostate biopsies. Here, we present results of experiments designed to study the impact of temporal order of the data in TeUS signals. We assess the impact of variations in temporal order on the ability to automatically distinguish benign prostate-tissue from malignant tissue. We have previously used Hidden Markov Models (HMMs) to model TeUS data, as HMMs capture temporal order in time series. In the work presented here, we use HMMs to model malignant and benign tissues; the models are trained and tested on TeUS signals while introducing variation to their temporal order. We first model the signals in their original temporal order, followed by modeling the same signals under various time rearrangements. We compare the performance of these models for tissue characterization. Our results show that models trained over the original order-preserving signals perform statistically significantly better for distinguishing between malignant and benign tissues, than those trained on rearranged signals. The performance degrades as the amount of temporal-variation increases. Specifically, accuracy of tissue characterization decreases from 85% using models trained on original signals to 62% using models trained and tested on signals that are completely temporally-rearranged. These results indicate the importance of order in characterization of tissue malignancy from TeUS data