Access to systemic anti-cancer therapies for women with secondary breast cancer-protocol for a mixed methods systematic review.

From Europe PMC via Jisc Publications RouterHistory: ppub 2021-07-01, epub 2021-07-23Publication status: PublishedBackgroundIt is well recognised that access and receipt of appropriate guideline recommended treatment with systemic anti-cancer therapies for secondary breast cancer is a key determinant in overall survival. Where there is disparity in access this may result in unwarranted variation and disparity in outcomes. Individual, clinical and wider contextual factors have been associated with these disparities, however this remains poorly understood for women with secondary breast cancer. The purpose of the review is to examine individual, clinical and contextual factors which influence access to evidence-based systemic anti-cancer therapies for women with secondary breast cancer. This will include barriers and facilitators for access and receipt of treatment and an exploration of women and clinicians experience and perspectives on access.MethodsA mixed methods approach with a segregated design will be used to examine and explore factors which influence access to systemic anti-cancer therapies for women with secondary breast cancer. Electronic databases to be searched from January 2000 onwards will be EBSCO CINAHL Plus, Ovid MEDLINE, Ovid EMBASE, PsychINFO and the Cochrane Library and JBI database. This will include NHS Evidence which will be searched for unpublished studies and gray literature. Title and abstract citations and full-text articles will be screened by the author and second reviewer. Data will be extracted by the author and validated by the second reviewer. An overarching synthesis will be produced which brings together quantitative and qualitative findings. Methodological quality and risk of bias will be assessed using the Mixed Methods Appraisal Tool.DiscussionUnderstanding individual, clinical and wider contextual factors associated with access and receipt of systemic anti-cancer therapies for secondary breast cancer is a complex phenomenon. These will be examined to determine any association with access. Review findings will be used to guide future research in this area and the development of an evidence-based service level intervention designed to address unwarranted variation in access based upon the Medical Research Council (MRC) approach to the development, implementation and evaluation of complex interventions.Systematic review registrationThe review protocol has been registered in PROSPERO CRD42020196490

Case management interventions seeking to counter radicalisation to violence and related forms of violence : a systematic review

This review was supported by a Campbell collaboration grant awarded to Sarah Marsden via Public Safety Canada.Background Increasingly, counter-radicalisation interventions are using case management approaches to structure the delivery of tailored services to those at risk of engaging in, or engaged in, violent extremism. This review sets out the evidence on case management tools and approaches and is made up of two parts with the following objectives. Objectives Part I: (1) Synthesise evidence on the effectiveness of case management tools and approaches in interventions seeking to counter radicalisation to violence. (2) Qualitatively synthesise research examining whether case management tools and approaches are implemented as intended, and the factors that explain how they are implemented. Part II: (3) Synthesise systematic reviews to understand whether case management tools and approaches are effective at countering non-terrorism related interpersonal or collective forms of violence. (4) Qualitatively synthesise research analysing whether case management tools and approaches are implemented as intended, and what influences how they are implemented. (5) Assess the transferability of tools and approaches used in wider violence prevention work to counter-radicalisation interventions. Search Methods Search terms tailored for Part I and Part II were used to search research repositories, grey literature sources and academic journals for studies published between 2000 and 2022. Searches were conducted in August and September 2022. Forward and backward citation searches and consultations with experts took place between September 2022 and February 2023. Studies in English, French, German, Russian, Swedish, Norwegian and Danish were eligible. Selection Criteria Part I: Studies had to report on a case management intervention, tool or approach, or on specific stages of the case management process. Only experimental and stronger quasi-experimental studies were eligible for inclusion in the analysis of effectiveness. The inclusion criteria for the analysis of implementation allowed for other quantitative designs and qualitative research. Part II: Systematic reviews examining a case management intervention, tool or approach, or stage(s) of the case management process focused on countering violence were eligible for inclusion. Data Collection and Analysis Part I: 47 studies were eligible for Part I. No studies met the inclusion criteria for Objective 1; all eligible studies related to Objective 2. Data from these studies was synthesised using a framework synthesis approach and presented narratively. Risk of bias was assessed using the CASP (for qualitative research) and EPHPP (for quantitative research) checklists. Part I: Eight reviews were eligible for Part II. Five reviews met the inclusion criteria for Objective 3, and seven for Objective 4. Data from the studies was synthesised using a framework synthesis approach and presented narratively. Risk of bias was assessed using the AMSTAR II tool. Findings Part I: No eligible studies examined effectiveness of tools and approaches. Seven studies examined the implementation of different approaches, or the assumptions underpinning interventions. Clearly defined theories of change were absent, however these interventions were assessed as being implemented in line with their own underlying logic. Forty-three studies analysed the implementation of tools during individual stages of the case management process, and forty-one examined the implementation of this process as-a-whole. Factors which influenced how individual stages and the case management process as a whole were implemented included strong multi-agency working arrangements; the inclusion of relevant knowledge and expertise, and associated training; and the availability of resources. The absence of these facilitators inhibited implementation. Additional implementation barriers included overly risk-oriented logics; public and political pressure; and broader legislation. Twenty-eight studies identified moderators that shaped how interventions were delivered, including delivery context; local context; standalone interventions; and client challenges. Part II: The effectiveness of two interventions – mentoring and multi-systemic therapy – in reducing violent outcomes were each assessed by one systematic review, whilst three reviews analysed the impact that the use of risk assessment tools (n = 2) and polygraphs (n = 1) had on outcomes. All these reviews reported mixed results. Comparable factors to those identified in Part I, such as staff training and expertise and delivery context, were found to shape implementation. On the basis of this modest sample, the research on interventions to counter non-terrorism related violence was assessed to be transferable to counter-radicalisation interventions. Authors' Conclusions The effectiveness of existing case management tools and approaches is poorly understood, and research examining the factors that influence how different approaches are implemented is limited. However, there is a growing body of research on the factors which facilitate or generate barriers to the implementation of case management interventions. Many of the factors and moderators relevant to countering radicalisation to violence also impact how case management tools and approaches used to counter other forms of violence are implemented. Research in this wider field seems to have transferable insights for efforts to counter radicalisation to violence. This review provides a platform for further research to test the impact of different tools, and the mechanisms by which they inform outcomes. This work will benefit from using the case management framework as a way of rationalising and analysing the range of tools, approaches and processes that make up case managed interventions to counter radicalisation to violence.Peer reviewe

The Last Mile and the Next Day:The changing times and spaces of shopping – implications for energy demand

There are many forms of shopping and all have consequences for the movement of goods and people, and for the patterns of energy demand that follow. In bringing different aspects of DEMAND research together we make three key points. First, different modes of shopping affect the practices and energy demands of consumers and of retailers, distributors and producers alike. Second, patterns of energy and travel demand vary depending on how aspects of shopping are organised in time and space. However, our third point is that different forms of shopping co-exist, overlap and change. Rather than trying to compare the energy demands of physical vs online shopping, as if these were coherent forms, the more important task is to explain escalating expectations of delivery and of what shopping entails. For all forms, what matters is how the ‘last mile’ is organised and why the ‘next day’ is so significant. In developing these points our aim is to inform and promote further research and reflection on the travel and energy demands associated with shopping in all its forms

NUIs for new worlds: new interaction forms and interfaces for mobile applications in developing countries

Mobile phones constitute the most ubiquitous computing platform in the developing world, and for the past decade it has been focus of many research efforts within Human Computer Interaction for Development (HCI4D). HCI4D has matured through a series of previous HCI related conferences and workshops and a growing body of work have established it as subfield of its own

Vfr Directly Activates exsA Transcription To Regulate Expression of the Pseudomonas aeruginosa Type III Secretion System

ABSTRACT The Pseudomonas aeruginosa cyclic AMP (cAMP)-Vfr system (CVS) is a global regulator of virulence gene expression. Regulatory targets include type IV pili, secreted proteases, and the type III secretion system (T3SS). The mechanism by which CVS regulates T3SS gene expression remains undefined. Single-cell expression studies previously found that only a portion of the cells within a population express the T3SS under inducing conditions, a property known as bistability. We now report that bistability is altered in a vfr mutant, wherein a substantially smaller fraction of the cells express the T3SS relative to the parental strain. Since bistability usually involves positive-feedback loops, we tested the hypothesis that virulence factor regulator (Vfr) regulates the expression of exsA . ExsA is the central regulator of T3SS gene expression and autoregulates its own expression. Although exsA is the last gene of the exsCEBA polycistronic mRNA, we demonstrate that Vfr directly activates exsA transcription from a second promoter (P exsA ) located immediately upstream of exsA . P exsA promoter activity is entirely Vfr dependent. Direct binding of Vfr to a P exsA promoter probe was demonstrated by electrophoretic mobility shift assays, and DNase I footprinting revealed an area of protection that coincides with a putative Vfr consensus-binding site. Mutagenesis of that site disrupted Vfr binding and P exsA promoter activity. We conclude that Vfr contributes to T3SS gene expression through activation of the P exsA promoter, which is internal to the previously characterized exsCEBA operon. IMPORTANCE Vfr is a cAMP-dependent DNA-binding protein that functions as a global regulator of virulence gene expression in Pseudomonas aeruginosa . Regulation by Vfr allows for the coordinate production of related virulence functions, such as type IV pili and type III secretion, required for adherence to and intoxication of host cells, respectively. Although the molecular mechanism of Vfr regulation has been defined for many target genes, a direct link between Vfr and T3SS gene expression had not been established. In the present study, we report that Vfr directly controls exsA transcription, the master regulator of T3SS gene expression, from a newly identified promoter located immediately upstream of exsA

Service Users’ Views and Experiences of Alcohol Relapse Prevention Treatment and Adherence: New Role for Pharmacists?

Aims: To understand service users’ views and experiences of alcohol relapse prevention medication, views of a telephone behaviouralmodification intervention delivered by pharmacists and the use of Contingency Management (CM) to support acamprosate adherence following assisted alcohol withdrawal.Methods: Four focus groups were conducted within four alcohol treatment and recovery groups across England (UK), with service users with lived experience of alcohol dependence (26 participants). Semi-structured topic guide was used to explore participants’ views and experiences of alcohol relapse prevention medication, a telephone behavioural modification medication intervention delivered by pharmacists, and the use of CM to support acamprosate adherence. These were audio-recorded, transcribed verbatim and thematically analysed inductively and deductively.Results: Four themes were identified: concerns about support and availability of alcohol relapse prevention medication; lack of knowledge and understanding about acamprosate treatment; positive perceptions of acamprosate adherence telephone support from pharmacists; and negative perceptions of CM to support acamprosate adherence. There were misunderstandings about acamprosate’s mode of action and strong negative beliefs about CM. However, most were positive about pharmacists’ new role to support acamprosate adherence.Conclusion: This study highlighted challenges service users face to commence alcohol relapse prevention medication. It appears service users could benefit from a pharmacist-led telephone intervention to improve understanding about acamprosate medication, particularly, if delivered in an engaging and motivating way

Service Users’ Views and Experiences of Alcohol Relapse Prevention Treatment and Adherence: New Role for Pharmacists?

Aims: To understand service users' views and experiences of alcohol relapse prevention medication, views of a telephone behavioural modification intervention delivered by pharmacists and the use of Contingency Management (CM) to support acamprosate adherence following assisted alcohol withdrawal. // Methods: Four focus groups were conducted within four alcohol treatment and recovery groups across England (UK), with service users with lived experience of alcohol dependence (26 participants). Semi-structured topic guide was used to explore participants' views and experiences of alcohol relapse prevention medication, a telephone behavioural modification medication intervention delivered by pharmacists, and the use of CM to support acamprosate adherence. These were audio-recorded, transcribed verbatim and thematically analysed inductively and deductively. // Results: Four themes were identified: concerns about support and availability of alcohol relapse prevention medication; lack of knowledge and understanding about acamprosate treatment; positive perceptions of acamprosate adherence telephone support from pharmacists; and negative perceptions of CM to support acamprosate adherence. There were misunderstandings about acamprosate's mode of action and strong negative beliefs about CM. However, most were positive about pharmacists' new role to support acamprosate adherence. // Conclusion: This study highlighted challenges service users face to commence alcohol relapse prevention medication. It appears service users could benefit from a pharmacist-led telephone intervention to improve understanding about acamprosate medication, particularly, if delivered in an engaging and motivating way

Midgut microbiota of the malaria mosquito vector Anopheles gambiae and Interactions with plasmodium falciparum Infection

The susceptibility of Anopheles mosquitoes to Plasmodium infections relies on complex interactions between the insect vector and the malaria parasite. A number of studies have shown that the mosquito innate immune responses play an important role in controlling the malaria infection and that the strength of parasite clearance is under genetic control, but little is known about the influence of environmental factors on the transmission success. We present here evidence that the composition of the vector gut microbiota is one of the major components that determine the outcome of mosquito infections. A. gambiae mosquitoes collected in natural breeding sites from Cameroon were experimentally challenged with a wild P. falciparum isolate, and their gut bacterial content was submitted for pyrosequencing analysis. The meta-taxogenomic approach revealed a broader richness of the midgut bacterial flora than previously described. Unexpectedly, the majority of bacterial species were found in only a small proportion of mosquitoes, and only 20 genera were shared by 80% of individuals. We show that observed differences in gut bacterial flora of adult mosquitoes is a result of breeding in distinct sites, suggesting that the native aquatic source where larvae were grown determines the composition of the midgut microbiota. Importantly, the abundance of Enterobacteriaceae in the mosquito midgut correlates significantly with the Plasmodium infection status. This striking relationship highlights the role of natural gut environment in parasite transmission. Deciphering microbe-pathogen interactions offers new perspectives to control disease transmission.Institut de Recherche pour le Developpement (IRD); French Agence Nationale pour la Recherche [ANR-11-BSV7-009-01]; European Community [242095, 223601]info:eu-repo/semantics/publishedVersio

Large UK retailers' initiatives to reduce consumers' emissions: a systematic assessment

In the interest of climate change mitigation, policy makers, businesses and non-governmental organisations have devised initiatives designed to reduce in-use emissions whilst, at the same time, the number of energy-consuming products in homes, and household energy consumption, is increasing. Retailers are important because they are at the interface between manufacturers of products and consumers and they supply the vast majority of consumer goods in developed countries like the UK, including energy using products. Large retailers have a consistent history of corporate responsibility reporting and have included plans and actions to influence consumer emissions within them. This paper adapts two frameworks to use them for systematically assessing large retailers’ initiatives aimed at reducing consumers’ carbon emissions. The Framework for Strategic Sustainable Development (FSSD) is adapted and used to analyse the strategic scope and coherence of these initiatives in relation to the businesses’ sustainability strategies. The ISM ‘Individual Social Material’ framework is adapted and used to analyse how consumer behaviour change mechanisms are framed by retailers. These frameworks are used to analyse eighteen initiatives designed to reduce consumer emissions from eight of the largest UK retail businesses, identified from publicly available data. The results of the eighteen initiatives analysed show that the vast majority were not well planned nor were they strategically coherent. Secondly, most of these specific initiatives relied solely on providing information to consumers and thus deployed a rather narrow range of consumer behaviour change mechanisms. The research concludes that leaders of retail businesses and policy makers could use the FSSD to ensure processes, and measurements are comprehensive and integrated, in order to increase the materiality and impact of their initiatives to reduce consumer emissions in use. Furthermore, retailers could benefit from exploring different models of behaviour change from the ISM framework in order to access a wider set of tools for transformative system change

Adjunctive Medication Management and Contingency Management to enhance adherence to acamprosate for alcohol dependence: the ADAM trial RCT

BackgroundAcamprosate is an effective and cost-effective medication for alcohol relapse prevention but poor adherence can limit its full benefit. Effective interventions to support adherence to acamprosate are therefore needed.ObjectivesTo determine the effectiveness of Medication Management, with and without Contingency Management, compared to Standard Support alone in enhancing adherence to acamprosate and the impact of adherence to acamprosate on abstinence and reduced alcohol consumption.DesignMulticentre, three-arm, parallel-group, randomised controlled clinical trial.SettingSpecialist alcohol treatment services in five regions of England (South East London, Central and North West London, Wessex, Yorkshire and Humber and West Midlands).ParticipantsAdults (aged 18 years or more), an International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, diagnosis of alcohol dependence, abstinent from alcohol at baseline assessment, in receipt of a prescription for acamprosate.Interventions(1) Standard Support, (2) Standard Support with adjunctive Medication Management provided by pharmacists via a clinical contact centre (12 sessions over 6 months), (3) Standard Support with adjunctive Medication Management plus Contingency Management that consisted of vouchers (up to £120) to reinforce participation in Medication Management. Consenting participants were randomised in a 2 : 1 : 1 ratio to one of the three groups using a stratified random permuted block method using a remote system. Participants and researchers were not blind to treatment allocation.Main outcome measuresPrimary outcome: self-reported percentage of medication taken in the previous 28 days at 6 months post randomisation. Economic outcome: EuroQol-5 Dimensions, a five-level version, used to calculate quality-adjusted life-years, with costs estimated using the Adult Service Use Schedule.ResultsOf the 1459 potential participants approached, 1019 (70%) were assessed and 739 (73 consented to participate in the study, 372 (50%) were allocated to Standard Support, 182 (25%) to Standard Support with Medication Management and 185 (25%) to Standard Support and Medication Management with Contingency Management. Data were available for 518 (70%) of participants at 6-month follow-up, 255 (68.5%) allocated to Standard Support, 122 (67.0%) to Standard Support and Medication Management and 141 (76.2%) to Standard Support and Medication Management with Contingency Management. The mean difference of per cent adherence to acamprosate was higher for those who received Standard Support and Medication Management with Contingency Management (10.6%, 95% confidence interval 19.6% to 1.6%) compared to Standard Support alone, at the primary end point (6-month follow-up). There was no significant difference in per cent days adherent when comparing Standard Support and Medication Management with Standard Support alone 3.1% (95% confidence interval 12.8% to −6.5%) or comparing Standard Support and Medication Management with Standard Support and Medication Management with Contingency Management 7.9% (95% confidence interval 18.7% to −2.8%). The primary economic analysis at 6 months found that Standard Support and Medication Management with Contingency Management was cost-effective compared to Standard Support alone, achieving small gains in quality-adjusted life-years at a lower cost per participant. Cost-effectiveness was not observed for adjunctive Medication Management compared to Standard Support alone. There were no serious adverse events related to the trial interventions reported.LimitationsThe trial’s primary outcome measure changed substantially due to data collection difficulties and therefore relied on a measure of self-reported adherence. A lower than anticipated follow-up rate at 12 months may have lowered the statistical power to detect differences in the secondary analyses, although the primary analysis was not impacted.ConclusionsMedication Management enhanced with Contingency Management is beneficial to patients for supporting them to take acamprosate