Clinical Remission in Severe Asthma : How to Move From Theory to Practice

ACKNOWLEDGMENTS Medical writing support was provided by Dan Jackson, PhD, CMPP, of CiTRUS Health Group, which was in accordance with Good Publication Practice (GPP4) guidelines. AstraZeneca (Cambridge, UK) funded this support. AMG and DBP both conceived and refined the topic for this manuscript. Both authors contributed to the discussion and revision of the content and approved the final version.Peer reviewedPostprin

Ends of groups : a computational approach

We develop ways in which we can find the number of ends of automatic groups and groups with solvable word problem. In chapter 1, we provide an introduction to ends, splittings, and computa- tion in groups. We also remark that the `JSJ problem' for finitely presented groups is not solvable. In chapter 2, we prove some geometrical properties of Cayley graphs that underpin later computational results. In chapter 3, we study coboundaries (sets of edges which disconnect the Cayley graph), and show how Stallings' theorem gives us finite objects from which we can calculate splittings. In chapter 4, we draw the results of previous chapters together to prove that we can detect zero, two, or infinitely many ends in groups with `good' automatic structures. We also prove that given an automatic group or a group with solvable word problem, if the group splits over a finite subgroup, we can detect this, and explicitly calculate a finite subgroup over which it splits. In chapter 5 we give an exposition of Gerasimov's result that one- endedness can be detected in hyperbolic groups. In chapter 6, we give an exposition of Epstein's boundary construction for graphs. We prove that a testable condition for automatic groups implies that this boundary is uniformly path-connected, and also prove that infinitely ended groups do not have uniformly path-connected boundary. As a result we are able to sometimes detect one endedness (and thus solve the problem of how many ends the group has)

Placental expression of pituitary hormones is an ancestral feature of therian mammals

<p>Abstract</p> <p>Background</p> <p>The placenta is essential for supplying nutrients and gases to the developing mammalian young before birth. While all mammals have a functional placenta, only in therian mammals (marsupials and eutherians) does the placenta closely appose or invade the uterine endometrium. The eutherian placenta secretes hormones that are structurally and functionally similar to pituitary growth hormone (GH), prolactin (PRL) and luteinizing hormone (LH). Marsupial and eutherian mammals diverged from a common ancestor approximately 125 to 148 million years ago and developed distinct reproductive strategies. As in eutherians, marsupials rely on a short-lived but functional placenta for embryogenesis.</p> <p>Results</p> <p>We characterized pituitary GH, GH-R, IGF-2, PRL and LHβ in a macropodid marsupial, the tammar wallaby, <it>Macropus eugenii</it>. These genes were expressed in the tammar placenta during the last third of gestation when most fetal growth occurs and active organogenesis is initiated. The mRNA of key growth genes GH, GH-R, IGF-2 and PRL were expressed during late pregnancy. We found significant up-regulation of GH, GH-R and IGF-2 after the start of the rapid growth phase of organogenesis which suggests that the placental growth hormones regulate the rapid phase of fetal growth.</p> <p>Conclusions</p> <p>This is the first demonstration of the existence of pituitary hormones in the marsupial placenta. Placental expression of these pituitary hormones has clearly been conserved in marsupials as in eutherian mammals, suggesting an ancestral origin of the evolution of placental expression and a critical function of these hormones in growth and development of all therian mammals.</p

A Charter to Fundamentally Change the Role of Oral Corticosteroids in the Management of Asthma

Asthma affects 339 million people worldwide, with an estimated 5–10% experiencing severe asthma. In emergency settings, oral corticosteroids (OCS) can be lifesaving, but acute and long-term treatment can produce clinically important adverse outcomes and increase the risk of mortality. Therefore, global guidelines recommend limiting the use of OCS. Despite the risks, research indicates that 40–60% of people with severe asthma are receiving or have received long-term OCS treatment. Although often perceived as a low-cost option, long-term OCS use can result in significant health impairments and costs owing to adverse outcomes and increased utilization of healthcare resources. Alternative treatment methods, such as biologics, may produce cost-saving benefits with a better safety profile. A comprehensive and concerted effort is necessary to tackle the continued reliance on OCS. Accordingly, a threshold for OCS use should be established to help identify patients at risk of OCS-related adverse outcomes. Receiving a total dose of more than 500 mg per year should trigger a review and specialist referral. Changes to national and local policies, following examples from other chronic diseases, will be crucial to achieving this goal. Globally, multiple barriers to change still exist, but specific steps have been identified to help clinicians reduce reliance on OCS. Implementing these changes will result in positive health outcomes for patients and social and economic benefits for societies.</p

Clinical Remission in Oral Corticosteroid (OCS)-dependent Patients with Severe Asthma : An Analysis of the ANDHI-IP and PONENTE Trials

Funding: This study was funded by AstraZeneca (Cambridge, UK).Peer reviewe

A randomised controlled feasibility study of group cognitive behavioural therapy for people with severe asthma

Objectives: Evidence for the efficacy of Cognitive Behavioural Therapy (CBT) in asthma is developing but it is not known if this translates to benefits in severe asthma or if a group approach is acceptable to this patient group. This study aimed to assess the feasibility and acceptability of Group-CBT in severe asthma. Method: This was a two-centre, randomised controlled parallel group feasibility study. Eligible participants (patients with severe asthma and a clinically significant diagnosis of anxiety and/or depression – Hospital Anxiety and Depression Scale (HAD) score greater than 8 for the anxiety or depression sub-scale) received Group-CBT in weekly sessions for eight consecutive weeks and usual care or usual care only. Follow-up was for 16 weeks and end points were: Asthma Quality of Life Questionnaire, Asthma Control Questionnaire, HAD, Dyspnoea-12, EuroQual-5D and EuroQuol-VAS. Results: 51 patients were randomised: 36% (51 out of 140) consent rate and 25% (13/51) attrition at week 16. Screening logs indicated that study take-up was influenced by patients living long distances from the treatment centre and inability to commit to the weekly demands of the programme. Drop-out was higher in Group-CBT compared due to inability to commit to the weekly programme because of poor health. Participants who contributed to focus group discussions reported that Group-CBT contributed to a better understanding of their illness and related approaches to anxiety management and acceptance of their asthma condition. Although weekly face-to-face sessions were challenging, this was the preferred method of delivery for these participants. Conclusions: This feasibility study shows that Group-CBT warrants further investigation as a potentially promising treatment option for patients with severe asthma. It has been possible but not easy to recruit and retain the sample. Options for a less demanding intervention schedule, such as less frequent face-to-face visits and the use of web-based interventions, require careful consideration

Systematic Literature Review of Systemic Corticosteroid Use for Asthma Management

Writing and editing assistance, including preparation of a draft manuscript under the direction and guidance of the authors, incorporating author feedback, and manuscript submission, was provided by Debra Scates, Ph.D., of JK Associates, Inc., and Michael A. Nissen, E.L.S., of AstraZeneca. This support was funded by AstraZeneca.Peer reviewedPublisher PD