A systematic review of interventions by healthcare professionals to improve management of non-communicable diseases and communicable diseases requiring long-term care in adults who are homeless

Objective: Identify, describe and appraise trials of interventions delivered by healthcare professionals to manage non-communicable diseases (NCDs) and communicable diseases that require long-term care or treatment (LT-CDs), excluding mental health and substance use disorders, in homeless adults. Design: Systematic review of randomised controlled trials (RCTs), non-RCTs and controlled before–after studies. Interventions characterised using Effective Practice and Organisation of Care (EPOC) taxonomy. Quality assessed using EPOC risk of bias criteria. Data sources: Database searches (MEDLINE, Embase, PsycINFO, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Applied Social Sciences Index and Abstracts (ASSIA) and Cochrane Central Register of Controlled Trials), hand searching reference lists, citation searches, grey literature and contact with study authors. Setting: Community. Participants: Adults (≥18 years) fulfilling European Typology of Homelessness criteria. Intervention: Delivered by healthcare professionals managing NCD and LT-CDs. Outcomes: Primary outcome: unscheduled healthcare utilisation. Secondary outcomes: mortality, biological markers of disease control, adherence to treatment, engagement in care, patient satisfaction, knowledge, self-efficacy, quality of life and cost-effectiveness. Results: 11 studies were included (8 RCTs, 2 quasi-experimental and 1 feasibility) involving 9–520 participants (67%–94% male, median age 37–49 years). Ten from USA and one from UK. Studies included various NCDs (n=3); or focused on latent tuberculosis (n=4); HIV (n=2); hepatitis C (n=1) or type 2 diabetes (n=1). All interventions were complex with multiple components. Four described theories underpinning intervention. Three assessed unscheduled healthcare utilisation: none showed consistent reduction in hospitalisation or emergency department attendance. Six assessed adherence to specific treatments, of which four showed improved adherence to latent tuberculosis therapy. Three concerned education case management, all of which improved disease-specific knowledge. No improvements in biological markers of disease (two studies) and none assessed mortality. Conclusions: Evidence for management of NCD and LT-CDs in homeless adults is sparse. Educational case-management interventions may improve knowledge and medication adherence. Large trials of theory-based interventions are needed, assessing healthcare utilisation and outcomes as well as assessment of biological outcomes and cost-effectiveness

Interventions by healthcare professionals to improve management of physical long-term conditions in adults who are homeless: a systematic review protocol

Introduction People experiencing homelessness are at increased risk of, and have poorer outcomes from, a range of physical long-term conditions (LTCs). It is increasingly recognised that interventions targeting people who are homeless should be tailored to the specific needs of this population. This systematic review aims to identify, describe and appraise trials of interventions that aim to manage physical LTCs in homeless adults and are delivered by healthcare professionals. Methods and analysis Seven electronic databases (Medline, EMBASE, Cochrane Central Register of Controlled Trials, Assia, Scopus, PsycINFO and CINAHL) will be searched from 1960 (or inception) to October 2016 and supplemented by forward citation searching, handsearching of reference lists and searching grey literature. Two reviewers will independently review titles, abstract and full-texts using DistillerSR software. Inclusion criteria include (1) homeless adults with any physical LTC, (2) interventions delivered by a healthcare professional (any professional trained to provide any form of healthcare, but excluding social workers and professionals without health-related training), (3) comparison with usual care or an alternative intervention, (4) report outcomes such as healthcare usage, physical and psychological health or well-being or cost-effectiveness, (5) randomised controlled trials, non-randomised controlled trials, controlled before-after studies. Quality will be assessed using the Cochrane EPOC Risk of Bias Tool. A meta-analysis will be performed if sufficient data are identified; however, we anticipate a narrative synthesis will be performed. Ethics and dissemination This review will synthesise existing evidence for interventions delivered by healthcare professionals to manage physical LTCs in adults who are homeless. The findings will inform the development of future interventions and research aiming to improve the management of LTCs for people experiencing homelessness. Ethical approval will not be required for this systematic review as it does not contain individual patient data. We will disseminate the results of this systematic review via conference presentations, healthcare professional networks, social media and peer-reviewed publication

How notifications affect engagement with a behaviour change app: Results from a micro-randomised trial

Background: Drink Less is a behavior change app to help higher-risk drinkers in the United Kingdom reduce their alcohol consumption. The app includes a daily notification asking users to “Please complete your drinks and mood diary,” yet we did not understand the causal effect of the notification on engagement nor how to improve this component of Drink Less. We developed a new bank of 30 new messages to increase users’ reflective motivation to engage with Drink Less. This study aimed to determine how standard and new notifications affect engagement. Objective: Our objective was to estimate the causal effect of the notification on near-term engagement, to explore whether this effect changed over time, and to create an evidence base to further inform the optimization of the notification policy. Methods: We conducted a micro-randomized trial (MRT) with 2 additional parallel arms. Inclusion criteria were Drink Less users who consented to participate in the trial, self-reported a baseline Alcohol Use Disorders Identification Test score of ≥8, resided in the United Kingdom, were aged ≥18 years, and reported interest in drinking less alcohol. Our MRT randomized 350 new users to test whether receiving a notification, compared with receiving no notification, increased the probability of opening the app in the subsequent hour, over the first 30 days since downloading Drink Less. Each day at 8 PM, users were randomized with a 30% probability of receiving the standard message, a 30% probability of receiving a new message, or a 40% probability of receiving no message. We additionally explored time to disengagement, with the allocation of 60% of eligible users randomized to the MRT (n=350) and 40% of eligible users randomized in equal number to the 2 parallel arms, either receiving the no notification policy (n=98) or the standard notification policy (n=121). Ancillary analyses explored effect moderation by recent states of habituation and engagement. Results: Receiving a notification, compared with not receiving a notification, increased the probability of opening the app in the next hour by 3.5-fold (95% CI 2.91-4.25). Both types of messages were similarly effective. The effect of the notification did not change significantly over time. A user being in a state of already engaged lowered the new notification effect by 0.80 (95% CI 0.55-1.16), although not significantly. Across the 3 arms, time to disengagement was not significantly different. Conclusions: We found a strong near-term effect of engagement on the notification, but no overall difference in time to disengagement between users receiving the standard fixed notification, no notification at all, or the random sequence of notifications within the MRT. The strong near-term effect of the notification presents an opportunity to target notifications to increase “in-the-moment” engagement. Further optimization is required to improve the long-term engagement. International Registered Report Identifier (IRRID): RR2-10.2196/1869

Cohesin is required for long-range enhancer action at the Shh locus

The regulatory landscapes of developmental genes in mammals can be complex, with enhancers spread over many hundreds of kilobases. It has been suggested that three-dimensional genome organisation, particularly topologically associating domains formed by cohesin-mediated loop extrusion, are important for enhancers to act over such large genomic distances. By coupling acute protein degradation with synthetic activation by targeted transcription factor recruitment, here we show that cohesin, but not CTCF, is required for activation of a target gene – Shh - by distant enhancers in mouse embryonic stem cells. Cohesin is not required for activation directly at the promoter or from an enhancer located closer to the Shh gene. Our findings support the hypothesis that chromatin compaction mediated by cohesin-mediated loop extrusion allows for genes to be activated by enhancers that are located many hundreds of kilobases away in the linear genome but suggests that cohesin is dispensable for more genomically close enhancers

A core outcome set for neonatal abstinence syndrome: Study protocol for a systematic review, parent interviews and a Delphi survey

Background: The prevalence of neonatal abstinence syndrome (NAS) is increasing globally resulting in an increased incidence of adverse neonatal outcomes and health system costs. Evidence regarding the effectiveness of NAS prevention and management strategies is very weak and further research initiatives are critically needed to support meta-analysis and clinical practice guidelines. In NAS research, the choice of outcomes and the use of valid, responsive and feasible measurement instruments are crucial. There is currently no consensus and evidence-based core outcome set (COS) for NAS. Methods/design: The development of the NAS-COS will include five stages led by an international Multidisciplinary Steering Committee: (1) qualitative interviews with parents/families and a systematic review (SR) to identify items for inclusion in a COS. The SR will also identify participants for the Delphi survey, (2) a three-round Delphi survey to gain expert opinion on the importance of health outcomes influencing NAS management decisions, (3), a consensus meeting to finalize the items and definitions with experts and COS users, (4) feasibility and pilot testing, development of the COS and explanatory document and (5) implementation planning. Discussion: Since standardized outcome measurement and reporting will improve NAS clinical research consistency, efficacy and impact, this COS will reflect the minimum set of health outcomes which should be measured in trials evaluating interventions for preventing or treating NAS

Early human B cell response to Ebola virus in four U.S. survivors of infection

The human B cell response to natural filovirus infections early after recovery is poorly understood. Previous serologic studies suggest that some Ebola virus survivors exhibit delayed antibody responses with low magnitude and quality. Here, we sought to study the population of individual memory B cells induced early in convalescence. We isolated monoclonal antibodies (MAbs) from memory B cells from four survivors treated for Ebola virus disease (EVD) 1 or 3 months after discharge from the hospital. At the early time points postrecovery, the frequency of Ebola-specific B cells was low and dominated by clones that were cross-reactive with both Ebola glycoprotein (GP) and with the secreted GP (sGP) form. Of 25 MAbs isolated from four donors, only one exhibited neutralization activity. This neutralizing MAb, designated MAb EBOV237, recognizes an epitope in the glycan cap of the surface glycoprotein. In vivo murine lethal challenge studies showed that EBOV237 conferred protection when given prophylactically at a level similar to that of the ZMapp component MAb 13C6. The results suggest that the human B cell response to EVD 1 to 3 months postdischarge is characterized by a paucity of broad or potent neutralizing clones. However, the neutralizing epitope in the glycan cap recognized by EBOV237 may play a role in the early human antibody response to EVD and should be considered in rational design strategies for new Ebola virus vaccine candidates

Prevention of Shoulder Problems trial (PROSPER) : Physiotherapist Manual [intervention manual and related materials]

This Physiotherapist Manual contains the relevant information to prepare physiotherapists for delivering the PROSPER exercise programme. The main concepts from each chapter will be covered in detail during your PROSPER training. This is your own reference manual with the relevant background information about trial processes and procedures. The trial is run by the Warwick Clinical Trials Unit based at the University of Warwick and is funded by the National Institute for Health Research (NIHR) under the Health Technology Assessment (HTA) funding stream. The purpose of the trial is to investigate whether postoperative exercise can improve function and quality of life in women at high risk of developing shoulder problems after breast cancer treatment. Some physiotherapists will have considerable experience of treating women with breast cancer or treating patients with musculoskeletal shoulder problems. However, not everyone will have the same skill and experience level, therefore this manual has been written to account for differences in background training, skill and clinical expertise. The aims of this Physiotherapist Manual are: - To explain the trial design; - To describe common side effects from breast cancer treatment; - To provide the research evidence for the PROSPER exercise intervention; - To describe procedures for the assessment and treatment of PROSPER study participants; - To describe trial documentation and reporting procedures. This manual has been produced to ‘standardise’ treatment and to reduce the risk of differences between physiotherapists and centres providing care. For all trial participants referred to your service, we ask that you adhere to the manual. This does not affect the care of non-trial participants, please treat your other patients in your usual way. You may even decide to use some of the approaches within the manual for non-trial patients. Thank you again for taking part in PROSPER. We hope you enjoy reading the manual and we very much look forward to working with you

Convergence of a common solution to broad ebolavirus neutralization by glycan cap directed human antibodies

Antibodies that target the glycan cap epitope on ebolavirus glycoprotein (GP) are common in the adaptive response of survivors. A subset is known to be broadly neutralizing, but the details of their epitopes and basis for neutralization is not well-understood. Here we present cryo-electron microscopy (cryo-EM) structures of several glycan cap antibodies that variably synergize with GP base-binding antibodies. These structures describe a conserved site of vulnerability that anchors the mucin-like domains (MLD) to the glycan cap, which we name the MLD-anchor and cradle. Antibodies that bind to the MLD-cradle share common features, including the use of IGHV1-69 and IGHJ6 germline genes, which exploit hydrophobic residues and form beta-hairpin structures to mimic the MLD-anchor, disrupt MLD attachment, destabilize GP quaternary structure and block cleavage events required for receptor binding. Our results collectively provide a molecular basis for ebolavirus neutralization by broadly reactive glycan cap antibodies