Findings from a pilot randomised trial of an asthma internet self-management intervention (RAISIN)

<b>Objective </b>To evaluate the feasibility of a phase 3 randomised controlled trial (RCT) of a website (Living Well with Asthma) to support self-management.<p></p> <b>Design and setting</b> Phase 2, parallel group, RCT, participants recruited from 20 general practices across Glasgow, UK. Randomisation through automated voice response, after baseline data collection, to website access for minimum 12 weeks or usual care.<p></p> <b>Participants </b>Adults (age≥16 years) with physician diagnosed, symptomatic asthma (Asthma Control Questionnaire (ACQ) score ≥1). People with unstable asthma or other lung disease were excluded.<p></p> <b>Intervention</b> Living Well with Asthma’ is a desktop/ laptop compatible interactive website designed with input from asthma/ behaviour change specialists, and adults with asthma. It aims to support optimal medication management, promote use of action plans, encourage attendance at asthma reviews and increase physical activity.<p></p> <b>Outcome measures</b> Primary outcomes were recruitment/retention, website use, ACQ and mini- Asthma Quality of Life Questionnaire (AQLQ). Secondary outcomes included patient activation, prescribing, adherence, spirometry, lung inflammation and health service contacts after 12 weeks. Blinding postrandomisation was not possible.<p></p> <b>Results </b>Recruitment target met. 51 participants randomised (25 intervention group). Age range 16–78 years; 75% female; 28% from most deprived quintile. 45/51 (88%; 20 intervention group) followed up. 19 (76% of the intervention group) used the website, for a mean of 18 min (range 0–49). 17 went beyond the 2 ‘core’ modules. Median number of logins was 1 (IQR 1–2, range 0–7). No significant difference in the prespecified primary efficacy measures of ACQ scores (−0.36; 95% CI −0.96 to 0.23; p=0.225), and mini-AQLQ scores (0.38; −0.13 to 0.89; p=0.136). No adverse events.<p></p> <b>Conclusions</b> Recruitment and retention confirmed feasibility; trends to improved outcomes suggest use of Living Well with Asthma may improve self-management in adults with asthma and merits further development followed by investigation in a phase 3 trial

Rifampicin and clarithromycin (extended release) versus rifampicin and streptomycin for limited Buruli ulcer lesions: a randomised, open-label, non-inferiority phase 3 trial.

BACKGROUND: Buruli ulcer is a neglected tropical disease caused by Mycobacterium ulcerans infection that damages the skin and subcutis. It is most prevalent in western and central Africa and Australia. Standard antimicrobial treatment with oral rifampicin 10 mg/kg plus intramuscular streptomycin 15 mg/kg once daily for 8 weeks (RS8) is highly effective, but streptomycin injections are painful and potentially harmful. We aimed to compare the efficacy and tolerability of fully oral rifampicin 10 mg/kg plus clarithromycin 15 mg/kg extended release once daily for 8 weeks (RC8) with that of RS8 for treatment of early Buruli ulcer lesions. METHODS: We did an open-label, non-inferiority, randomised (1:1 with blocks of six), multicentre, phase 3 clinical trial comparing fully oral RC8 with RS8 in patients with early, limited Buruli ulcer lesions. There were four trial sites in hospitals in Ghana (Agogo, Tepa, Nkawie, Dunkwa) and one in Benin (Pobè). Participants were included if they were aged 5 years or older and had typical Buruli ulcer with no more than one lesion (caterories I and II) no larger than 10 cm in diameter. The trial was open label, and neither the investigators who took measurements of the lesions nor the attending doctors were masked to treatment assignment. The primary clinical endpoint was lesion healing (ie, full epithelialisation or stable scar) without recurrence at 52 weeks after start of antimicrobial therapy. The primary endpoint and safety were assessed in the intention-to-treat population. A sample size of 332 participants was calculated to detect inferiority of RC8 by a margin of 12%. This study was registered with ClinicalTrials.gov, NCT01659437. FINDINGS: Between Jan 1, 2013, and Dec 31, 2017, participants were recruited to the trial. We stopped recruitment after 310 participants. Median age of participants was 14 years (IQR 10-29) and 153 (52%) were female. 297 patients had PCR-confirmed Buruli ulcer; 151 (51%) were assigned to RS8 treatment, and 146 (49%) received oral RC8 treatment. In the RS8 group, lesions healed in 144 (95%, 95% CI 91 to 98) of 151 patients, whereas lesions healed in 140 (96%, 91 to 99) of 146 patients in the RC8 group. The difference in proportion, -0·5% (-5·2 to 4·2), was not significantly greater than zero (p=0·59), showing that RC8 treatment is non-inferior to RS8 treatment for lesion healing at 52 weeks. Treatment-related adverse events were recorded in 20 (13%) patients receiving RS8 and in nine (7%) patients receiving RC8. Most adverse events were grade 1-2, but one (1%) patient receiving RS8 developed serious ototoxicity and ended treatment after 6 weeks. No patients needed surgical resection. Four patients (two in each study group) had skin grafts. INTERPRETATION: Fully oral RC8 regimen was non-inferior to RS8 for treatment of early, limited Buruli ulcer and was associated with fewer adverse events. Therefore, we propose that fully oral RC8 should be the preferred therapy for early, limited lesions of Buruli ulcer. FUNDING: WHO with additional support from MAP International, American Leprosy Missions, Fondation Raoul Follereau France, Buruli ulcer Groningen Foundation, Sanofi-Pasteur, and BuruliVac

Polynomial-sized Semidefinite Representations of Derivative Relaxations of Spectrahedral Cones

We give explicit polynomial-sized (in $n$ and $k$) semidefinite representations of the hyperbolicity cones associated with the elementary symmetric polynomials of degree $k$ in $n$ variables. These convex cones form a family of non-polyhedral outer approximations of the non-negative orthant that preserve low-dimensional faces while successively discarding high-dimensional faces. More generally we construct explicit semidefinite representations (polynomial-sized in $k,m$, and $n$) of the hyperbolicity cones associated with $k$th directional derivatives of polynomials of the form $p(x) = \det(\sum_{i=1}^{n}A_i x_i)$ where the $A_i$ are $m\times m$ symmetric matrices. These convex cones form an analogous family of outer approximations to any spectrahedral cone. Our representations allow us to use semidefinite programming to solve the linear cone programs associated with these convex cones as well as their (less well understood) dual cones.Comment: 20 pages, 1 figure. Minor changes, expanded proof of Lemma

Advances in multispectral and hyperspectral imaging for archaeology and art conservation

Multispectral imaging has been applied to the field of art conservation and art history since the early 1990s. It is attractive as a noninvasive imaging technique because it is fast and hence capable of imaging large areas of an object giving both spatial and spectral information. This paper gives an overview of the different instrumental designs, image processing techniques and various applications of multispectral and hyperspectral imaging to art conservation, art history and archaeology. Recent advances in the development of remote and versatile multispectral and hyperspectral imaging as well as techniques in pigment identification will be presented. Future prospects including combination of spectral imaging with other noninvasive imaging and analytical techniques will be discussed

The Role of Innate APOBEC3G and Adaptive AID Immune Responses in HLA-HIV/SIV Immunized SHIV Infected Macaques

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Mapping suitability for Buruli ulcer at fine spatial scales across Africa: A modelling study.

Buruli ulcer (BU) is a disabling and stigmatising neglected tropical disease (NTD). Its distribution and burden are unknown because of underdiagnosis and underreporting. It is caused by Mycobacterium ulcerans, an environmental pathogen whose environmental niche and transmission routes are not fully understood. The main control strategy is active surveillance to promote early treatment and thus limit morbidity, but these activities are mostly restricted to well-known endemic areas. A better understanding of environmental suitability for the bacterium and disease could inform targeted surveillance, and advance understanding of the ecology and burden of BU. We used previously compiled point-level datasets of BU and M. ulcerans occurrence, evidence for BU occurrence within national and sub-national areas, and a suite of relevant environmental covariates in a distribution modelling framework. We fitted relationships between BU and M. ulcerans occurrence and environmental predictors by applying regression and machine learning based algorithms, combined in an ensemble model to characterise the optimal ecological niche for the disease and bacterium across Africa at a resolution of 5km x 5km. Proximity to waterbodies was the strongest predictor of suitability for BU, followed potential evapotranspiration. The strongest predictors of suitability for M. ulcerans were deforestation and potential evapotranspiration. We identified patchy foci of suitability throughout West and Central Africa, including areas with no previous evidence of the disease. Predicted suitability for M. ulcerans was wider but overlapping with that of BU. The estimated population living in areas predicted suitable for the bacterium and disease was 46.1 million. These maps could be used to inform burden estimations and case searches which would generate a more complete understanding of the spatial distribution of BU in Africa, and may guide control programmes to identify cases beyond the well-known endemic areas

Comparison of Efficacy and Safety of Ciclosporin to Prednisolone in the Treatment of Erythema Nodosum Leprosum: Two Randomised, Double Blind, Controlled Pilot Studies in Ethiopia.

BACKGROUND: Erythema Nodosum Leprosum (ENL) is a serious complication of leprosy. It is normally treated with high dose steroids, but its recurrent nature leads to prolonged steroid usage and associated side effects. There is little evidence on the efficacy of alternative treatments for ENL, especially for patients who have become steroid resistant or have steroid side effects. These two pilot studies compare the efficacy and side effect profile of ciclosporin plus prednisolone against prednisolone alone in the treatment of patients with either new ENL or chronic and recurrent ENL. METHODS AND RESULTS: Thirteen patients with new ENL and twenty patients with chronic ENL were recruited into two double-blinded randomised controlled trials. Patients were randomised to receive ciclosporin and prednisolone or prednisolone treatment only. Patients with acute ENL had a delay of 16 weeks in the occurrence of ENL flare-up episode, with less severe flare-ups and decreased requirements for additional prednisolone. Patients with chronic ENL on ciclosporin had the first episode of ENL flare-up 4 weeks earlier than those on prednisolone, as well as more severe ENL flare-ups requiring 2.5 times more additional prednisolone. Adverse events attributable to prednisolone were more common that those attributable to ciclosporin. CONCLUSIONS: This is the first clinical trial on ENL management set in the African context, and also the first trial in leprosy to use patients' assessment of outcomes. Patients on ciclosporin showed promising results in the management of acute ENL in this small pilot study. But ciclosporin, did not appear to have a significant steroid-sparing effects in patients with chronic ENL, which may have been due to the prolonged use of steroids in these patients in combination with a too rapid decrease of steroids in patients given ciclosporin. Further research is needed to determine whether the promising results of ciclosporin in acute ENL can be reproduced on a larger scale