Exposed! Management of MDR-TB household contacts in an evidence light era.

Until the three ongoing randomised controlled trials of preventive therapy are completed, there remains a large knowledge gap about how individuals known to have been exposed to multidrug-resistant TB (MDR-TB) should be managed. The evolving paradigms and improving outcomes from treatment of active MDR-TB disease play in to discussions about the relative merits and importance of intensive surveillance and/or preventive therapy for MDR-TB contacts

The theoretical basis of a nationally implemented type 2 diabetes prevention programme: how is the programme expected to produce changes in behaviour?

From Springer Nature via Jisc Publications RouterHistory: received 2020-11-25, registration 2021-05-04, accepted 2021-05-04, online 2021-05-13, pub-electronic 2021-05-13, collection 2021-12Publication status: PublishedFunder: Health Services and Delivery Research Programme; doi: http://dx.doi.org/10.13039/501100002001; Grant(s): 16/48/07Abstract: Background: It is considered best practice to provide clear theoretical descriptions of how behaviour change interventions should produce changes in behaviour. Commissioners of the National Health Service Diabetes Prevention Programme (NHS-DPP) specified that the four independent provider organisations must explicitly describe the behaviour change theory underpinning their interventions. The nationally implemented programme, launched in 2016, aims to prevent progression to Type 2 diabetes in high-risk adults through changing diet and physical activity behaviours. This study aimed to: (a) develop a logic model describing how the NHS-DPP is expected to work, and (b) document the behaviour change theories underpinning providers’ NHS-DPP interventions. Methods: A logic model detailing how the programme should work in changing diet and activity behaviours was extracted from information in three specification documents underpinning the NHS-DPP. To establish how each of the four providers expected their interventions to produce behavioural changes, information was extracted from their programme plans, staff training materials, and audio-recorded observations of mandatory staff training courses attended in 2018. All materials were coded using Michie and Prestwich’s Theory Coding Scheme. Results: The NHS-DPP logic model included information provision to lead to behaviour change intentions, followed by a self-regulatory cycle including action planning and monitoring behaviour. None of the providers described an explicit logic model of how their programme will produce behavioural changes. Two providers stated their programmes were informed by the COM-B (Capability Opportunity Motivation – Behaviour) framework, the other two described targeting factors from multiple theories such as Self-Regulation Theory and Self-Determination Theory. All providers cited examples of proposed links between some theoretical constructs and behaviour change techniques (BCTs), but none linked all BCTs to specified constructs. Some discrepancies were noted between the theory described in providers’ programme plans and theory described in staff training. Conclusions: A variety of behaviour change theories were used by each provider. This may explain the variation between providers in BCTs selected in intervention design, and the mismatch between theory described in providers’ programme plans and staff training. Without a logic model describing how they expect their interventions to work, justification for intervention contents in providers’ programmes is not clear

Telomere dysfunction accurately predicts clinical outcome in chronic lymphocytic leukaemia, even in patients with early stage disease

© 2014 John Wiley & Sons Ltd. Defining the prognosis of individual cancer sufferers remains a significant clinical challenge. Here we assessed the ability of high-resolution single telomere length analysis (STELA), combined with an experimentally derived definition of telomere dysfunction, to predict the clinical outcome of patients with chronic lymphocytic leukaemia (CLL). We defined the upper telomere length threshold at which telomere fusions occur and then used the mean of the telomere 'fusogenic' range as a prognostic tool. Patients with telomeres within the fusogenic range had a significantly shorter overall survival (P  <  0·0001; Hazard ratio [HR] = 13·2, 95% confidence interval [CI]  = 11·6-106·4) and this was preserved in early-stage disease patients (P  <  0·0001, HR=19·3, 95% CI = 17·8-802·5). Indeed, our assay allowed the accurate stratification of Binet stage A patients into those with indolent disease (91% survival at 10 years) and those with poor prognosis (13% survival at 10 years). Furthermore, patients with telomeres above the fusogenic mean showed superior prognosis regardless of their IGHV mutation status or cytogenetic risk group. In keeping with this finding, telomere dysfunction was the dominant variable in multivariate analysis. Taken together, this study provides compelling evidence for the use of high-resolution telomere length analysis coupled with a definition of telomere dysfunction in the prognostic assessment of CLL

The Fidelity of Training in Behaviour Change Techniques to Intervention Design in a National Diabetes Prevention Programme

Background The National Health Service Diabetes Prevention Programme (NHS-DPP) is a behavioural intervention for people identified as high risk for developing type 2 diabetes that has been rolled out across England. The present study evaluates whether the four commercial providers of the NHS-DPP train staff to deliver behaviour change technique (BCT) content with fidelity to intervention plans. Method One set of mandatory training courses across the four NHS-DPP providers (seven courses across 13 days) was audio-recorded, and all additional training materials used were collected. Recordings and training materials were coded for BCT content using the BCT Taxonomy v1. BCTs and depth of training (e.g. instruction, demonstration, practice) of BCT content was checked against providers’ intervention plans. Results Ten trainers and 78 trainees were observed, and 12 documents examined. The number of unique BCTs in audio recordings and associated training materials ranged from 19 to 44 across providers, and staff were trained in 53 unique BCTs across the whole NHS-DPP. Staff were trained in 66% of BCTs that were in intervention plans, though two providers trained staff in approximately half of BCTs to be delivered. The most common way that staff were trained in BCT delivery was through instruction. Training delivery style (e.g. experiential versus educational) varied between providers. Conclusion Observed training evidences dilution from providers’ intervention plans. NHS-DPP providers should review their training to ensure staff are trained in all key intervention components, ensuring thorough training of BCTs (e.g. demonstrating and practicing how to deliver) to enhance BCT delivery

The Fidelity of Training in Behaviour Change Techniques to Intervention Design in a National Diabetes Prevention Programme

From Springer Nature via Jisc Publications RouterHistory: accepted 2021-01-19, registration 2021-01-19, pub-electronic 2021-02-09, online 2021-02-09, pub-print 2021-12Publication status: PublishedFunder: Health Services and Delivery Research Programme; doi: http://dx.doi.org/10.13039/501100002001; Grant(s): 16/48/07Abstract: Background: The National Health Service Diabetes Prevention Programme (NHS-DPP) is a behavioural intervention for people identified as high risk for developing type 2 diabetes that has been rolled out across England. The present study evaluates whether the four commercial providers of the NHS-DPP train staff to deliver behaviour change technique (BCT) content with fidelity to intervention plans. Method: One set of mandatory training courses across the four NHS-DPP providers (seven courses across 13 days) was audio-recorded, and all additional training materials used were collected. Recordings and training materials were coded for BCT content using the BCT Taxonomy v1. BCTs and depth of training (e.g. instruction, demonstration, practice) of BCT content was checked against providers’ intervention plans. Results: Ten trainers and 78 trainees were observed, and 12 documents examined. The number of unique BCTs in audio recordings and associated training materials ranged from 19 to 44 across providers, and staff were trained in 53 unique BCTs across the whole NHS-DPP. Staff were trained in 66% of BCTs that were in intervention plans, though two providers trained staff in approximately half of BCTs to be delivered. The most common way that staff were trained in BCT delivery was through instruction. Training delivery style (e.g. experiential versus educational) varied between providers. Conclusion: Observed training evidences dilution from providers’ intervention plans. NHS-DPP providers should review their training to ensure staff are trained in all key intervention components, ensuring thorough training of BCTs (e.g. demonstrating and practicing how to deliver) to enhance BCT delivery

School physical activity intervention effect on adolescents' performance in mathematics

Purpose: The primary aim of this study was to test the effect of a school-based physical activity intervention on adolescents’ performance in mathematics. A secondary aim was to explore potential mechanisms that might explain the intervention effect. Methods: The Activity and Motivation in Physical EDucation intervention was evaluated using a two-arm cluster randomized controlled trial in 14 secondary schools located in low socioeconomic areas of Western Sydney, Australia. Study participants (n = 1173) were grade 8 students (mean age = 12.94 yr, SD = 0.54). The multicomponent intervention was designed to help teachers maximize students’ opportunities for moderate-to-vigorous physical activity (MVPA) during physical education (PE) and enhance students’ motivation toward PE. Mathematics performance was assessed as part of national testing in grade 7, which was the year before the trial began and then again in grade 9. Potential mediators were: (i) proportion of PE lesson time that students spent in MVPA and leisure time MVPA (%), measured using Actigraph GT3X+ accelerometers, and (ii) students’ self-reported engagement (behavioral, emotional, and cognitive) during mathematics lessons. Mediators were assessed at baseline (grade 8) and follow-up (grade 9, 14–15 months after baseline). Results: The effect of the intervention on mathematics performance was small-to-medium (β = 0.16, P < 0.001). An intervention effect was observed for MVPA% in PE (β = 0.59, P < 0.001), but not for leisure time MVPA or any of the engagement mediators. There were no significant associations between changes in potential mediators and mathematics performance. Conclusions: The Activity and Motivation in Physical EDucation intervention had a significant positive effect on mathematics performance in adolescents. However, findings should be interpreted with caution as the effect was small and not associated with changes in hypothesized mediators

Feasibility of an mobile application as a tool for multidrug-resistant tuberculosis contact monitoring in Peru.

This study aimed to validate an ODK digital mobile application (ODK-DMA) in contacts exposed to multidrug-resistant tuberculosis (MDR-TB) in Lima, Peru. Using a questionnaire in an application on a mobile device, we registered 129 household contacts of 29 index cases of MDR-TB under treatment in 10 health facilities in South Lima in August 2018. The mean time of registration per contact was found to be 4 minutes. The prevalence of active TB symptoms among MDR-TB contacts was 3.1%. An acceptability questionnaire was completed by 31 respondents; all reported feeling comfortable or very comfortable with recording their data in the ODK-DMA, although 10% expressed concerns about confidentiality. We concluded that the ODK-DMA was a feasible and acceptable tool for registering household contacts exposed to cases with MDR-TB. Future studies should consider the use of mobile platforms for the monitoring of MDR-TB contacts

CCR8 Expression Defines Tissue-Resident Memory T Cells in Human Skin

Human skin harbors two major T cell compartments of equal size that are distinguished by expression of the chemokine receptor CCR8. In vitro studies have demonstrated that CCR8 expression is regulated by TCR engagement and the skin tissue microenvironment. To extend these observations, we examined the relationship between CCR8+ and CCR8− skin T cells in vivo. Phenotypic, functional, and transcriptomic analyses revealed that CCR8+ skin T cells bear all the hallmarks of resident memory T cells, including homeostatic proliferation in response to IL-7 and IL-15, surface expression of tissue localization (CD103) and retention (CD69) markers, low levels of inhibitory receptors (programmed cell death protein 1, Tim-3, LAG-3), and a lack of senescence markers (CD57, killer cell lectin-like receptor subfamily G member 1). In contrast, CCR8− skin T cells are heterogeneous and comprise variable numbers of exhausted (programmed cell death protein 1+), senescent (CD57+, killer cell lectin-like receptor subfamily G member 1+), and effector (T-bethi, Eomeshi) T cells. Importantly, conventional and high-throughput sequencing of expressed TCR β-chain (TRB) gene rearrangements showed that these CCR8-defined populations are clonotypically distinct, suggesting unique ontogenies in response to separate antigenic challenges and/or stimulatory conditions. Moreover, CCR8+ and CCR8− skin T cells were phenotypically stable in vitro and displayed similar levels of telomere erosion, further supporting the likelihood of a nonlinear differentiation pathway. On the basis of these results, we propose that long-lived memory T cells in human skin can be defined by the expression of CCR8

Quantitative MRI outcome measures in CMT1A using automated lower limb muscle segmentation

BACKGROUND: Lower limb muscle magnetic resonance imaging (MRI) obtained fat fraction (FF) can detect disease progression in patients with Charcot-Marie-Tooth disease 1A (CMT1A). However, analysis is time-consuming and requires manual segmentation of lower limb muscles. We aimed to assess the responsiveness, efficiency and accuracy of acquiring FF MRI using an artificial intelligence-enabled automated segmentation technique. METHODS: We recruited 20 CMT1A patients and 7 controls for assessment at baseline and 12 months. The three-point-Dixon fat water separation technique was used to determine thigh-level and calf-level muscle FF at a single slice using regions of interest defined using Musclesense, a trained artificial neural network for lower limb muscle image segmentation. A quality control (QC) check and correction of the automated segmentations was undertaken by a trained observer. RESULTS: The QC check took on average 30 seconds per slice to complete. Using QC checked segmentations, the mean calf-level FF increased significantly in CMT1A patients from baseline over an average follow-up of 12.5 months (1.15%±1.77%, paired t-test p=0.016). Standardised response mean (SRM) in patients was 0.65. Without QC checks, the mean FF change between baseline and follow-up, at 1.15%±1.68% (paired t-test p=0.01), was almost identical to that seen in the corrected data, with a similar overall SRM at 0.69. CONCLUSIONS: Using automated image segmentation for the first time in a longitudinal study in CMT, we have demonstrated that calf FF has similar responsiveness to previously published data, is efficient with minimal time needed for QC checks and is accurate with minimal corrections needed