Modern innovative solutions to improve outcomes in severe asthma : Protocol for a mixed methods observational comparison of clinical outcomes in mission versus current care delivery

Background: Asthma that is poorly controlled and undertreated can progress to more severe disease that is associated with high levels of unscheduled care that requires high-cost therapy, leading to a significant health economic burden. The identification and appropriate referral to a specialist asthma service is also often delayed by several months or years because of poor recognition and understanding of symptom severity. Current severe asthma services may take several months to provide a comprehensive multidisciplinary assessment, often necessitating multiple hospital visits and costing up to £5000 per patient. Objective: This study aims to evaluate whether a new service model could identify poorly controlled and potentially severe asthma much earlier in the patient pathway, and then compare clinical outcomes between this new care model with standard care. Methods: Modern Innovative Solutions to Improve Outcomes in (MISSION) Severe Asthma is a novel service model developed by asthma specialists from Portsmouth and Southampton severe asthma services. MISSION Severe Asthma identified patients with poorly controlled disease from general practice databases who had not been under secondary outpatient care in the last 12 months or who were not known to secondary care. In 1- or 2-stop assessments, a thorough review of diagnosis, disease phenotype, and control is undertaken, and clinical outcomes collected at baseline. Results: A variety of clinical outcomes will be collected to assess the service model. The results will be reported in February 2020. Conclusions: This protocol outlines a mixed methods study to assess the impact on disease control, unscheduled health care usage, and quality of life in patients seen in the MISSION clinic compared with a closely matched cohort who declined to attend

A minimal peach type II chlorophyll a/b-binding protein promoter retains tissue-specificity and light regulation in tomato

<p>Abstract</p> <p>Background</p> <p>Promoters with tissue-specificity are desirable to drive expression of transgenes in crops to avoid accumulation of foreign proteins in edible tissues/organs. Several photosynthetic promoters have been shown to be strong regulators of expression of transgenes in light-responsive tissues and would be good candidates for leaf and immature fruit tissue-specificity, if expression in the mature fruit were minimized.</p> <p>Results</p> <p>A minimal peach chlorophyll <it>a/b</it>-binding protein gene (<it>Lhcb2*Pp1</it>) promoter (Cab19) was isolated and fused to an <it>uid</it>A (β-glucuronidase [GUS]) gene containing the PIV2 intron. A control vector carrying an enhanced <it>mas</it>35S CaMV promoter fused to <it>uid</it>A was also constructed. Two different orientations of the Cab19::GUS fusion relative to the left T-DNA border of the binary vector were transformed into tomato. Ten independent regenerants of each construct and an untransformed control line were assessed both qualitatively and quantitatively for GUS expression in leaves, fruit and flowers, and quantitatively in roots.</p> <p>Conclusion</p> <p>The minimal CAB19 promoter conferred GUS activity primarily in leaves and green fruit, as well as in response to light. GUS activity in the leaves of both Cab19 constructs averaged about 2/3 that observed with <it>mas</it>35S::GUS controls. Surprisingly, GUS activity in transgenic green fruit was considerably higher than leaves for all promoter constructs; however, in red, ripe fruit activities were much lower for the Cab19 promoter constructs than the <it>mas</it>35S::GUS. Although GUS activity was readily detectable in flowers and roots of <it>mas</it>35S::GUStransgenic plants, little activity was observed in plants carrying the Cab19 promoter constructs. In addition, the light-inducibility of the Cab19::GUS constructs indicated that all the requisite <it>cis</it>-elements for light responsiveness were contained on the Cab19 fragment. The minimal Cab19 promoter retains both tissue-specificity and light regulation and can be used to drive expression of foreign genes with minimal activity in mature, edible fruit.</p

Exploring the waveform characteristics of tidal breathing carbon dioxide, measured using the N-Tidal C device in different breathing conditions (The General Breathing Record Study): protocol for an observational, longitudinal study

Background: In an increasingly comorbid population, there are significant challenges to diagnosing the cause of breathlessness, and once diagnosed, considerable difficulty in detecting deterioration early enough to provide effective intervention. The burden of the breathless patient on the health care economy is substantial, with asthma, chronic heart failure, and pneumonia affecting over 6 million people in the United Kingdom alone. Furthermore, these patients often have more than one contributory factor to their breathlessness symptoms, with conditions such as dysfunctional breathing pattern disorders—an under-recognized component. Current methods of diagnosing and monitoring breathless conditions can be extensive and difficult to perform. As a consequence, home monitoring is poorly complied with. In contrast, capnography (the measurement of tidal breath carbon dioxide) is performed during normal breathing. There is a need for a simple, easy-to-use, personal device that can aid in the diagnosis and monitoring of respiratory and cardiac causes of breathlessness.Objective: The aim of this study was to explore the use of a new, handheld capnometer (called the N-Tidal C) in different conditions that cause breathlessness. We will study whether the tidal breath carbon dioxide (TBCO2) waveform, as measured by the N-Tidal C, has different characteristics in a range of respiratory and cardiac conditions.Methods: We will perform a longitudinal, observational study of the TBCO2 waveform (capnogram) as measured by the N-Tidal C capnometer. Participants with a confirmed diagnosis of asthma, breathing pattern disorders, chronic heart failure, motor neurone disease, pneumonia, as well as volunteers with no history of lung disease will be asked to provide twice daily, 75-second TBCO2 collection via the N-Tidal C device for 6 months duration. The collated capnograms will be correlated with the underlying diagnosis and disease state (stable or exacerbation) to determine if there are different TBCO2 characteristics that can distinguish different respiratory and cardiac causes of breathlessness.Results: This study’s recruitment is ongoing. It is anticipated that the results will be available in late 2018.Conclusions: The General Breathing Record Study will provide an evaluation of the use of capnography as a diagnostic and home-monitoring tool for various diseases

Predicting survival in malignant pleural mesothelioma using routine clinical and laboratory characteristics

Introduction The prognosis of malignant pleural mesothelioma (MPM) is poor, with a median survival of 8–12 months. The ability to predict prognosis in MPM would help clinicians to make informed decisions regarding treatment and identify appropriate research opportunities for patients. The aims of this study were to examine associations between clinical and pathological information gathered during routine care, and prognosis of patients with MPM, and to develop a 6-month mortality risk prediction model.Methods A retrospective cohort study of patients diagnosed with MPM at Queen Alexandra Hospital, Portsmouth, UK between December 2009 and September 2013. Multivariate analysis was performed on routinely available histological, clinical and laboratory data to assess the association between different factors and 6-month survival, with significant associations used to create a model to predict the risk of death within 6 months of diagnosis with MPM.Results 100 patients were included in the analysis. Variables significantly associated with patient survival in multivariate analysis were age (HR 1.31, 95% CI 1.09 to 1.56), smoking status (current smoker HR 3.42, 95% CI 1.11 to 4.20), chest pain (HR 2.14, 95% CI 1.23 to 3.72), weight loss (HR 2.13, 95% CI 1.18 to 3.72), platelet count (HR 1.05, 95% CI 1.00 to 1.10), urea (HR 2.73, 95% CI 1.31 to 5.69) and adjusted calcium (HR 1.47, 95% CI 1.10 to 1.94). The resulting risk model had a c-statistic value of 0.76. A Hosmer-Lemeshow test confirmed good calibration of the model against the original dataset.Conclusion Risk of death at 6 months in patients with a confirmed diagnosis of MPM can be predicted using variables readily available in clinical practice. The risk prediction model we have developed may be used to influence treatment decisions in patients with MPM. Further validation of the model requires evaluation of its performance on a separate dataset

The promoter from SlREO, a highly-expressed, root-specific Solanum lycopersicum gene, directs expression to cortex of mature roots

Root-specific promoters are valuable tools for targeting transgene expression, but many of those already described have limitations to their general applicability. We present the expression characteristics of SlREO, a novel gene isolated from tomato (Solanum lycopersicum L.). This gene was highly expressed in roots but had a very low level of expression in aerial plant organs. A 2.4-kb region representing the SlREO promoter sequence was cloned upstream of the uidA GUS reporter gene and shown to direct expression in the root cortex. In mature, glasshouse-grown plants this strict root specificity was maintained. Furthermore, promoter activity was unaffected by dehydration or wounding stress but was somewhat suppressed by exposure to NaCl, salicylic acid and jasmonic acid. The predicted protein sequence of SlREO contains a domain found in enzymes of the 2-oxoglutarate and Fe(II)-dependent dioxygenase superfamily. The novel SlREO promoter has properties ideal for applications requiring strong and specific gene expression in the bulk of tomato root tissue growing in soil, and is also likely to be useful in other Solanaceous crop

Modern innovative solutions to improve outcomes in asthma, breathlessness, and chronic obstructive pulmonary disease (MISSION ABC): protocol for a mixed-methods study

Background: A high proportion of the costs for respiratory diseases are generated by a relatively small group of patients with severe disease (recognized or unrecognized) or complex problems that include multimorbidity, at-risk behaviors, and socioeconomic disadvantage. These patients often struggle to engage with the structured, proactive, care approaches for chronic disease management advocated for asthma and chronic obstructive pulmonary disease (COPD), resulting in repeated emergency use of both primary and secondary health care. An integrated approach for the management of complex patients, incorporating both specialist and primary care teams’ expertise, may be effective in improving outcomes for such high-risk patients. However, the evidence is mixed, and there is a need for evaluation of models of integrated care in routine “real-world” clinical settings.Objective: This mixed-methods protocol examines the implementation of a novel integrated care model for patients with airways disease and undifferentiated breathlessness by using both quantitative and qualitative evaluation of processes, patient and health care professional experiences, and clinical outcomes throughout the clinic cycles. It aims to establish whether Modern Innovative Solutions to Improve Outcomes in Asthma, Breathlessness, and Chronic Obstructive Pulmonary Disease (MISSION ABC), including innovative diagnostic and self-management tools, can deliver improvements in health service use and clinical outcomes for the different patient groups (asthma, breathlessness, and COPD) and compares the 12-month period prior to the first patient visit and the 6-month period following the last visit.Methods: A combination of study designs is required to evaluate all aspects of the service: participatory action research approach, involving real-time evaluation at each clinic to inform subsequent clinics; before-and-after study for patient outcomes before and after clinic attendance; and qualitative methods (interviews and focus groups).Results: The results will be compiled and published in April 2019.Conclusions: Evaluation of the clinic cycles will include consideration of qualitative data from patients, carers, and health care professionals in addition to quantitative outcomes for service implementation and patient factors. The long-term impact of the service will be evaluated using clinical and health service outcomes