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Background National clinical audit programmes aim to improve patient care by reviewing performance against explicit standards and directing action towards areas not meeting those standards. Their impact can be improved by (1) optimising feedback content and format, (2) strengthening audit cycles and (3) embedding randomised trials evaluating different ways of delivering feedback. Objectives The objectives were to (1) develop and evaluate the effects of modifications to feedback on recipient responses, (2) identify ways of strengthening feedback cycles for two national audits and (3) explore opportunities, costs and benefits of national audit participation in a programme of trials. Design An online fractional factorial screening experiment (objective 1) and qualitative interviews (objectives 2 and 3). Setting and participants Participants were clinicians and managers involved in five national clinical audits – the National Comparative Audit of Blood Transfusions, the Paediatric Intensive Care Audit Network, the Myocardial Ischaemia National Audit Project, the Trauma Audit & Research Network and the National Diabetes Audit – (objective 1); and clinicians, members of the public and researchers (objectives 2 and 3). Interventions We selected and developed six online feedback modifications through three rounds of user testing. We randomised participants to one of 32 combinations of the following recommended specific actions: comparators reinforcing desired behaviour change; multimodal feedback; minimised extraneous cognitive load for feedback recipients; short, actionable messages followed by optional detail; and incorporating ‘the patient voice’ (objective 1). Main outcome measures The outcomes were intended actions, including enactment of audit standards (primary outcome), comprehension, user experience and engagement (objective 1). Results For objective 1, the primary analysis included 638 randomised participants, of whom 566 completed the outcome questionnaire. No modification independently increased intended enactment of audit standards. Minimised cognitive load improved comprehension (+0.1; p = 0.014) and plans to bring audit findings to colleagues’ attention (+0.13, on a –3 to +3 scale; p = 0.016). We observed important cumulative synergistic and antagonistic interactions between modifications, participant role and national audit. The analysis in objective 2 included 19 interviews assessing the Trauma Audit Research Network and the National Diabetes Audit. The identified ways of strengthening audit cycles included making performance data easier to understand and guiding action planning. The analysis in objective 3 identified four conditions for effective collaboration from 31 interviews: compromise – recognising capacity and constraints; logistics – enabling data sharing, audit quality and funding; leadership – engaging local stakeholders; and relationships – agreeing shared priorities and needs. The perceived benefits of collaboration outweighed the risks. Limitations The online experiment assessed intended enactment as a predictor of actual clinical behaviour. Interviews and surveys were subject to social desirability bias. Conclusions National audit impacts may be enhanced by strengthening all aspects of feedback cycles, particularly effective feedback, and considering how different ways of reinforcing feedback act together. Future work Embedded randomised trials evaluating different ways of delivering feedback within national clinical audits are acceptable and may offer efficient, evidence-based and cumulative improvements in outcomes. Trial registration This trial is registered as ISRCTN41584028. Funding details This project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme and will be published in full in Health and Social Care Delivery Research; Vol. 10, No. 15. See the NIHR Journals Library website for further project information.

BackgroundThe rise in opioid prescribing in primary care represents a significant public health challenge, associated with increased psychosocial problems, hospitalisations, and mortality. An evidence-based bimonthly feedback intervention to reduce opioid prescribing was developed and implemented, targeting 316 general practices in West Yorkshire over 1 year.AimTo understand how general practice staff received and responded to the feedback intervention.Design and settingQualitative process evaluation involving semi-structured interviews, guided by Normalisation Process Theory (NPT), of primary care healthcare professionals targeted by feedback.MethodParticipants were purposively recruited according to baseline opioid prescribing levels and degree of change following feedback. Interview data were coded to NPT constructs, and thematically analysed.ResultsInterviews were conducted with 21 staff from 20 practices. Reducing opioid prescribing was recognised as a priority. While high achievers had clear structures for quality improvement, feedback encouraged some less structured practices to embed changes. The non-prescriptive nature of the feedback reports allowed practices to develop strategies consistent with their own ways of working and existing resources. Practice concerns were allayed by the credibility of the reports and positive experiences of reducing opioid prescribing. The scale, frequency, and duration of feedback may have ensured a good overall level of practice population reach.ConclusionThe intervention engaged general practice staff in change by targeting an issue of emerging concern, and allowing adaption to different ways of working. Practice efforts to reduce opioid prescribing were reinforced by regular feedback, credible comparative data showing progress, and shared experiences of patient benefit.

Ethically , behavior analysts are required to use the least aversive and restrictive procedures capable of managing behaviors of concern. This article introduces and discusses a multi-element paradigm for devising support plans that include ecological, positive programming, and focused-support proactive strategies for reducing the frequency of problem behavior occurrence. It also includes reactive strategies, i.e., separate independent variables. In this paradigm, reactive strategies are aimed solely at getting rapid, safe control over the incident, thereby reducing measured and quantified episodic severity. Behavior analysts who publish in mainstream behavioral journals do not always make it explicit how they, in fact, successfully employed non-aversive reactive procedures to achieve rapid/safe control over the severity of a behavioral incident. Three examples of published studies in the behavioral literature which successfully, though only implicitly, used non-aversive reactive strategies (NARS) to reduce the severity of the behaviors of concern are described. The multi-element paradigm discussed in the present article is illustrated by the support plans that address the challenging behavior of three children in a pre-school setting, using both proactive and reactive strategies. Reactive strategies were used for the purpose of reducing episodic severity (ES) and proactive strategies were aimed at reducing the frequency of occurrence. Following a comprehensive functional analysis and assessment (CFA) and the implementation of a multi-element behavior support (MEBS) plan, results show successful outcomes without the need for any aversive or restrictive procedures. When addressing severe behaviors of concern, in addition to reducing behavioral occurrence, safety should also be improved by reducing ES as a measured outcome and as a function of the reactive strategies employed, including in many cases, the use of strategic capitulation, i.e., providing the identified reinforcer for the target behavior.

Background Over the last 10 years HENRY has been working to reduce and prevent child obesity by training health and early years professionals to deliver its evidence-based programme to parents. The aim and unique contribution of this study was to evaluate whether training volunteers to deliver this programme on a one-to-one basis was feasible. Methods Mixed-methods service evaluation with parent-reported pre- and post-programme outcomes and focus groups conducted with parents and volunteer facilitators. The programme consisted of 8 one-to-one sessions delivered weekly by volunteers (n = 18) to build food and activity-related knowledge, skills, and understanding, and improve parenting efficacy, and parent and child eating and physical activity. Programmes took place at parent’s (n = 69) home or local community venues in four London boroughs, United Kingdom. Parent-reported parenting efficacy, emotional wellbeing, eating, and physical activity data were captured, alongside parent ratings of the programme and volunteer ratings of the training. Parent and volunteer focus groups explored involvement, expectations, and experiences of the programme, training and delivery, feedback, and impact. Results Parents were mostly female, had varied ethnic backgrounds, and were often not working but well educated. There were statistically significant improvements of a medium-to-large size in parent and child emotional wellbeing, parenting efficacy, fruit and vegetable consumption, family eating and food purchasing behaviours. Parent ratings of the programme were positive and qualitative data highlighted the holistic nature of the programme, which focused on more than just food, and the relationships with volunteers as key facets. Volunteers were also mostly female, had varied ethnic backgrounds, and were often well educated, but more likely to be employed than parents. Volunteers rated the training and delivery as useful in enabling them to deliver the programme confidently and for their own wellbeing. Despite finding some sessions challenging emotionally, volunteers reported positive family lifestyle improvements by parents and children and that the experience would be useful for future employment. Conclusions It is feasible to recruit and train volunteers to deliver a structured preschool obesity prevention programme, which parents considered acceptable and enjoyable, with preliminary reports of parent and child benefits.

Focus of Presentation There is international concern over rising trends in opioid prescribing, largely attributed to prescribing for chronic non-cancer pain. We conducted a controlled interrupted time series study on anonymised, aggregated practice data to evaluate the effect of the Campaign to Reduce Opioid Prescribing (CROP) in reducing the number of patients taking opioid medication in West Yorkshire UK practices targeted by the feedback intervention, compared to practices outside of West Yorkshire. We will discuss the methodological challenges addressed in the collection and analysis of these data, and the implications for using routine data in trials. Findings Primary care data sources for feedback interventions include large-scale databases (General Practice Research Database), high-level nationally gathered databases (OpenPrescribing.com) or data extracted directly from electronic health records (EHR). We will discuss the implications of the different sources of data and compare the results from each, in understanding the impact of the feedback intervention of reducing opioid prescribing over time. The consequences of the heterogeneity of the data sources on the interrupted time series analysis undertaken will also be discussed and solutions outlined. Conclusions/Implications Routine data are heterogeneous, with different purposes, structures and collection methods, which have considerable implications on their use, analysis and interpretation. Researchers need to understand that the utility of routine data sources have implications (both practically and methodologically) in conducting pragmatic trials, which should be considered when planning and conducting future studies using routine data.

Background Childhood obesity is a major public health concern. In the UK, a quarter of children are overweight or obese at age five years. Overweight and obese children are more likely to develop serious health issues such as diabetes later in life. Consequently, there is an urgent need for effective, early obesity prevention and intervention. This study investigated the impact of an eight‐week child obesity intervention ‐ HENRY (Health Exercise Nutrition for the Really Young) ‐ designed to help parents with preschool children develop the skills and knowledge needed to improve family lifestyle and wellbeing. We were particularly interested in exploring the potential mechanisms by which HENRY may have a positive impact. Method Focus groups (n=7, total participants = 39) were completed with mothers attending the HENRY programme at one of seven locations across England. They took place within two weeks of programme completion. Follow‐up telephone interviews were completed with a subsample of participants (n=10) between 17 and 21 weeks later. Results Parents consistently reported enhanced self‐efficacy in terms of improved confidence in their ability to encourage healthier behaviours such as eating fruit and increasing physical activity, and improvements to family health behaviours. Many changes were reportedly sustained at follow‐up. Data provided insights into the potential mechanisms that created the conditions for the positive changes. Participants described the importance of mutual support, being listened to by facilitators and encouragement to identify their own ideas. Their comments indicated the success of a solution‐focused, strength‐based, partnership approach to supporting family lifestyle change. Conclusion The results of this study contribute to the body of evidence suggesting that HENRY may have a positive impact on parenting and family lifestyle behaviour. Although data were collected in 2011, the findings contribute to an understanding of the components of effective obesity prevention in young children.

IF 15.132 (2017); International audience; The introduction of novel agents has led to major improvements in clinical outcomes for patients with multiple myeloma. To shorten evaluation times for new treatments, health agencies are currently examining minimal residual disease (MRD) as a surrogate end point in clinical trials. We assessed the prognostic value of MRD, measured during maintenance therapy by next-generation sequencing (NGS). MRD negativity was defined as the absence of tumor plasma cell within 1 000 000 bone marrow cells (

Continental-scale models of malaria climate suitability typically couple well-established temperature-response models with basic estimates of vector habitat availability using rainfall as a proxy. Here we show that across continental Africa, the estimated geographic range of climatic suitability for malaria transmission is more sensitive to the precipitation threshold than the thermal response curve applied. To address this problem we use downscaled daily climate predictions from seven GCMs to run a continental-scale hydrological model for a process-based representation of mosquito breeding habitat availability. A more complex pattern of malaria suitability emerges as water is routed through drainage networks and river corridors serve as year-round transmission foci. The estimated hydro-climatically suitable area for stable malaria transmission is smaller than previous models suggest and shows only a very small increase in state-of-the-art future climate scenarios. However, bigger geographical shifts are observed than with most rainfall threshold models and the pattern of that shift is very different when using a hydrological model to estimate surface water availability for vector breeding., Prior studies mapping climatologically suitable areas for malaria transmission have used relatively simple thresholds for precipitation. Here the authors show that when models incorporate hydrological processes a more complex pattern of malaria suitability emerges in Africa and future shifts in suitability are more pronounced.

Background The Barotse floodplains of the upper Zambezi River and its tributaries are a highly dynamic environment, with seasonal flooding and transhumance presenting a shifting mosaic of potential larval habitat and human and livestock blood meals for malaria vector mosquitoes. However, limited entomological surveillance has been undertaken to characterize the vector community in these floodplains and their environs. Such information is necessary as, despite substantial deployment of insecticide-treated nets (ITNs) and indoor residual spraying (IRS) against Anopheles vectors, malaria transmission persists across Barotseland in Zambia’s Western Province. Methods Geographically extensive larval surveys were undertaken in two health districts along 102 km of transects, at fine spatial resolution, during a dry season and following the peak of the successive wet season. Larvae were sampled within typical Anopheles flight range of human settlements and identified through genetic sequencing of cytochrome c oxidase I and internal transcribed spacer two regions of mitochondrial and nuclear DNA. This facilitated detailed comparison of taxon-specific abundance patterns between ecological zones differentiated by hydrological controls. Results An unexpected paucity of primary vectors was revealed, with An. gambiae s.l. and An. funestus representing < 2% of 995 sequenced anophelines. Potential secondary vectors predominated in the vector community, primarily An. coustani group species and An. squamosus. While the distribution of An. gambiae s.l. in the study area was highly clustered, secondary vector species were ubiquitous across the landscape in both dry and wet seasons, with some taxon-specific relationships between abundance and ecological zones by season. Conclusions The diversity of candidate vector species and their high relative abundance observed across diverse hydro-ecosystems indicate a highly adaptable transmission system, resilient to environmental variation and, potentially, interventions that target only part of the vector community. Larval survey results imply that residual transmission of malaria in Barotseland is being mediated predominantly by secondary vector species, whose known tendencies for crepuscular and outdoor biting renders them largely insensitive to prevalent vector control methods. Graphical Abstract

BackgroundDissemination of clinical guidelines is necessary but seldom sufficient by itself to ensure the reliable uptake of evidence-based practice. There are further challenges in implementing multiple clinical guidelines and clinical practice recommendations in the pressurised environment of general practice.ObjectivesWe aimed to develop and evaluate an implementation package that could be adapted to support the uptake of a range of clinical guideline recommendations and be sustainably integrated within general practice systems and resources. Over five linked work packages, we developed ‘high-impact’ quality indicators to show where a measurable change in clinical practice can improve patient outcomes (work package 1), analysed adherence to selected indicators (work package 2), developed an adaptable implementation package (work package 3), evaluated the effects and cost-effectiveness of adapted implementation packages targeting four indicators (work package 4) and examined intervention fidelity and mechanisms of action (work package 5).Setting and participantsHealth-care professionals and patients from general practices in West Yorkshire, UK.DesignWe reviewed recommendations from existing National Institute for Health and Care Excellence clinical guidance and used a multistage consensus process, including 11 professionals and patients, to derive a set of ‘high-impact’ evidence-based indicators that could be measured using routinely collected data (work package 1). In 89 general practices that shared data, we found marked variations and scope for improvement in adherence to several indicators (work package 2). Interviews with 60 general practitioners, practice nurses and practice managers explored perceived determinants of adherence to selected indicators and suggested the feasibility of adapting an implementation package to target different indicators (work package 3). We worked with professional and patient panels to develop four adapted implementation packages. These targeted risky prescribing involving non-steroidal anti-inflammatory and antiplatelet drugs, type 2 diabetes control, blood pressure control and anticoagulation for atrial fibrillation. The implementation packages embedded behaviour change techniques within audit and feedback, educational outreach and (for risky prescribing) computerised prompts. We randomised 178 practices to implementation packages targeting either diabetes control or risky prescribing (trial 1), or blood pressure control or anticoagulation (trial 2), or to a further control (non-intervention) group, and undertook economic modelling (work package 4). In trials 1 and 2, practices randomised to the implementation package for one indicator acted as control practices for the other package, and vice versa. A parallel process evaluation included a further eight practices (work package 5).Main outcome measuresTrial primary end points at 11 months comprised achievement of all recommended levels of glycated haemoglobin, blood pressure and cholesterol; risky prescribing levels; achievement of recommended blood pressure; and anticoagulation prescribing.ResultsWe recruited 178 (73%) out of 243 eligible general practices. We randomised 80 practices to trial 1 (40 per arm) and 64 to trial 2 (32 per arm), with 34 non-intervention controls. The risky prescribing implementation package reduced risky prescribing (odds ratio 0.82, 97.5% confidence interval 0.67 to 0.99;p = 0.017) with an incremental cost-effectiveness ratio of £2337 per quality-adjusted life-year. The other three packages had no effect on primary end points. The process evaluation suggested that trial outcomes were influenced by losses in fidelity throughout intervention delivery and enactment, and by the nature of the targeted clinical and patient behaviours.LimitationsOur programme was conducted in one geographical area; however, practice and patient population characteristics are otherwise likely to be sufficiently diverse and typical to enhance generalisability to the UK. We used an ‘opt-out’ approach to recruit general practices to the randomised trials. Subsequently, our trial practices may have engaged with the implementation package less than if they had actively volunteered. However, this approach increases confidence in the wider applicability of trial findings as it replicates guideline implementation activities under standard conditions.ConclusionsThis pragmatic, rigorous evaluation indicates the value of an implementation package targeting risky prescribing. In broad terms, an adapted ‘one-size-fits-all’ approach did not consistently work, with no improvement for other targeted indicators.Future workThere are challenges in designing ‘one-size-fits-all’ implementation strategies that are sufficiently robust to bring about change in the face of difficult clinical contexts and fidelity losses. We recommend maximising feasibility and ‘stress testing’ prior to rolling out interventions within a definitive evaluation. Our programme has led on to other work, adapting audit and feedback for other priorities and evaluating different ways of delivering feedback to improve patient care.Trial registrationCurrent Controlled Trials ISRCTN91989345.FundingThis project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full inProgramme Grants for Applied Research; Vol. 8, No. 4. See the NIHR Journals Library website for further project information.

The availability of water at the ground surface for vector mosquito larval habitats is a critical environmental control of malaria transmission. While ambient air temperature controls the rate of several components of the malaria transmission cycle, extensive laboratory and field studies mean that suitable temperature ranges are well established. In contrast, estimation of surface water availability from current global datasets remains challenging. Instead, monthly rainfall is typically used as a proxy for habitat availability; a threshold of 80 mm per month has gained traction as a proxy for breeding habitat in continental-scale models of malaria climate suitability in Africa and has been applied across the globe. However, since complex and spatially variable hydrological processes (e.g. infiltration, evaporation, soil moisture storage, transfer through and storage in river networks) are omitted, a wide variety of rainfall thresholds are found in the literature that leads to large differences in environmental suitability estimates. Moreover, irrigated areas have been observed to provide suitable year-round habitat for Anopheles mosquitos but are not included in such models. Here we show that across continental Africa, the estimated geographic range of climatic suitability for malaria transmission is more sensitive to precipitation thresholds than the thermal response curves applied. To address this problem and provide a more physical-basis for larval habitat estimation, we use daily climate predictions from seven downscaled general circulation models to run a continental-scale hydrological model (Lisflood) for a process-based representation of mosquito breeding habitat availability. A more complex pattern of malaria climatic suitability emerges as water is routed through drainage networks and river corridors serve as year-round transmission foci. The area estimated to be hydro-climatically suitable for stable malaria transmission is smaller than previous models suggest; however, more people are found in longer-transmission season areas due to higher-density populations along rivers and in irrigated areas. Hydro-climatic predictions of malaria suitable areas show only a very small increase in state-of-the-art future climate scenarios; however, bigger geographical shifts are observed than with most rainfall threshold models and the pattern of that shift is very different when a hydrological model is used to estimate surface water availability for vector breeding.

The Barotse floodplain in the Western Province of Zambia, is a major feature of the Upper Zambezi River, covering an area of 11,000km2, and is inundated annually by a flood cycle that ranges from minimum values in September, to peak levels in April. The annual flooding of the area provides a number of challenges, and critically is a significant component of the life cycle of mosquitos, the principle vector for the transmission of malaria. A research project, FLOODMAL, has been developed to apply process based modelling approaches to the life cycle of the mosquito in the floodplain. A significant component of this approach is the development of a 1D-2D model which can be used to predict the formation of water bodies that are essential to the mosquito breeding cycle. This research presents the uncertainties associated with developing the flood model, with an emphasis on model performance through simulation time. In a typical model exercise, the calibration of input parameters are associated with ensuring that model performance is optimised for representing the peak of a flood event. This can be at the cost of providing a consistent level of model performance throughout a simulation, which is essential in this research.Using the LISFLOOD-FP computer code, and TanDEM-X1 terrain data, a baseline model of the Barotse floodplain was developed for the 2009 and 2018 events. A set of initial model runs identified key processes to be represented in the model, including evaporation and infiltration. The calibration of the model was focused on defining parameters for surface roughness, channel roughness, evaporation, infiltration, and defining channel topography. A number of datasets were available for model calibration, such as LandSAT imagery to compare observed and modelled extent at various points throughout the year, and downstream river gauge data. To further understand the uncertainties associated with the modelling, sensitivity analysis was undertaken using an emulator- based approach to define the contribution of the input parameters to overall model variance. The results indicate that parameters that control the movement of water across the floodplain (surface roughness) are generally the most significant of the inputs at all points in the year, although the level of this significance changes at different phases.

BackgroundPatient and public involvement (PPI) is often an essential requirement for research funding. Distinctions can be drawn between clinical research, which generally focuses on patients, and implementation research, which generally focuses on health professional behaviour. There is uncertainty about the role of PPI in this latter field. We explored and defined the roles of PPI in implementation research to inform relevant good practice guidance.MethodsWe used a structured consensus process using a convenience sample panel of nine experienced PPI and two researcher members. We drew on available literature to identify 21 PPI research roles. The panel rated their agreement with roles independently online in relation to both implementation and clinical research. Disagreements were discussed at a face-to-face meeting prior to a second online rating of all roles. Median scores were calculated and a final meeting held to review findings and consider recommendations.ResultsTen panellists completed the consensus process. For clinical research, there was strong support and consensus for the role of PPI throughout most of the research process. For implementation research, there were eight roles with consensus and strong support, seven roles with consensus but weaker support and six roles with no consensus. There were more disagreements relating to PPI roles in implementation research compared with clinical research. PPI was rated as contributing less to the design and management of implementation research than for clinical research.ConclusionsThe roles of PPI need to be tailored according to the nature of research to ensure authentic and appropriate involvement. We provide a framework to guide the planning, conduct and reporting of PPI in implementation research, and encourage further research to evaluate its use.

Complete remission (CR) rates for multiple myeloma (MM) have increased to 60% with current treatment approaches, including high dose melphalan-based autologous stem cell transplant (ASCT) and novel agents, and are associated with improved survival.[1][1]–[3][2] Despite this improvement, highly

Background. Doctors have a special role in helping patients make lifestyle changes, and they are more credible and effective if they are role models. Yet few medical schools have incorporated lifestyle medicine into their curricula. We ascertained the influence of a lifestyle medicine curriculum during the first year of medical school. Methods. The curriculum, involving 140 students, consisted of one intensive day at medical school entry and 16 hours of teaching 8 months later. It addressed students’ own lifestyle choices and topics related to lifestyle medicine. A survey was delivered at the beginning and end of the academic year. Results. A total of 114 students completed the first survey and 64 the second. They rated the course highly for personal and professional value. At baseline, students exhibited lifestyle behaviors typical for young adults and showed an appreciation of the physician’s role in lifestyle change. However, over time they showed a significant reduction in quality of lifestyle, with increased stress, weight gain, and fast food consumption and less exercise. Conclusions. Although lifestyle medicine knowledge is valued by medical students, a 24-hour intensive lifestyle medicine curriculum delivered over 3 days appears to be ineffective in preventing worsening lifestyle behaviors over the course of the year. This is especially concerning as physicians are unlikely to provide effective guidance if they cannot sustain healthy behaviors themselves.

Efflux pumps contribute to antibiotic resistance in Gram-negative pathogens. Correspondingly, efflux pump inhibitors (EPIs) may reverse this resistance. D13-9001 specifically inhibits MexAB-OprM in Pseudomonas aeruginosa Mutants with decreased susceptibility to MexAB-OprM inhibition by D13-9001 were identified, and these fell into two categories: those with alterations in the target MexB (F628L and ΔV177) and those with an alteration in a putative sensor kinase of unknown function, PA1438 (L172P). The alterations in MexB were consistent with reported structural studies of the D13-9001 interaction with MexB. The PA1438L172P alteration mediated a >150-fold upregulation of MexMN pump gene expression and a >50-fold upregulation of PA1438 and the neighboring response regulator gene, PA1437. We propose that these be renamed mmnR and mmnS for M ex MN r egulator and M ex MN sensor, respectively. MexMN was shown to partner with the outer membrane channel protein OprM and to pump several β-lactams, monobactams, and tazobactam. Upregulated MexMN functionally replaced MexAB-OprM to efflux these compounds but was insusceptible to inhibition by D13-9001. MmnSL172P also mediated a decrease in susceptibility to imipenem and biapenem that was independent of MexMN-OprM. Expression of oprD, encoding the uptake channel for these compounds, was downregulated, suggesting that this channel is also part of the MmnSR regulon. Transcriptome sequencing (RNA-seq) of cells encoding MmnSL172P revealed, among other things, an interrelationship between the regulation of mexMN and genes involved in heavy metal resistance.

One in five children in England are overweight/obese at school entry. Tackling obesity is therefore a priority. Right from the Start with HENRY is a widely-commissioned programme delivered by trained facilitators to small groups of parents over eight weekly sessions. It is designed to provide parents of infants and preschool children with the skills, knowledge and confidence required for a healthier family lifestyle. The aim of this work was to investigate programme impact using data collected routinely for quality control purposes.Analysis of routinely collected pre-post data from programmes delivered in the UK from January 2012 to February 2014.Data were analysed from 144 programmes, including questionnaires relating to parenting, family eating behaviours, dietary intake, and physical activity/screen time.Over 24 months, 1100 parents attended programmes running in 86 locations. 788 (72%) completed5 sessions of whom 624 (79%) provided baseline and completion questionnaires. Parents reported increases in healthiness of family lifestyle, parenting attributes, and emotional wellbeing following attendance (all P .001). Both parents and children were reported to have increased their daily fruit/vegetable consumption, and reduced their consumption of high fat/sugar foods (both P .001). There were also positive changes in eating behaviours, physical activity (P .001) and children's screen time (P .001).Significant changes were reported in all domains similar to those reported in a previous, smaller study in locations selected for experience and quality. The HENRY approach appears to have a beneficial impact even when delivered at scale in non-selected locations. Such changes, if maintained, may serve to protect against later obesity.

Assessing uncertainty is a critical part of understanding and developing flood inundation models for use in risk assessment. Typically, uncertainties are investigated by comparing the effects of an ensemble of key model inputs, such as friction values and hydrographic uncertainties, on model outputs. In this study, an approach is adopted that also consider the uncertainty associated with the computational models. Using the LISFLOOD-FP code, which contains multiple methods for solving floodplain flow, two test cases with different hydraulic characteristics are used in a systematic uncertainty analysis. An ensemble of inputs including cell size, hydrological uncertainty, and representation of buildings are assessed for impact on modelling results. Results show the numerical complexity is a significant source of uncertainty in complex flow regimes, but this reduces in typical fluvial flood events. The method of assessing the modelling output is also found to be important in determining the overall influence of parameters.

Background Interpreting evaluations of complex interventions can be difficult without sufficient description of key intervention content. We aimed to develop an implementation package for primary care which could be delivered using typically available resources and could be adapted to target determinants of behaviour for each of four quality indicators: diabetes control, blood pressure control, anticoagulation for atrial fibrillation and risky prescribing. We describe the development and prospective verification of behaviour change techniques (BCTs) embedded within the adaptable implementation packages. Methods We used an over-lapping multi-staged process. We identified evidence-based, candidate delivery mechanisms—mainly audit and feedback, educational outreach and computerised prompts and reminders. We drew upon interviews with primary care professionals using the Theoretical Domains Framework to explore likely determinants of adherence to quality indicators. We linked determinants to candidate BCTs. With input from stakeholder panels, we prioritised likely determinants and intervention content prior to piloting the implementation packages. Our content analysis assessed the extent to which embedded BCTs could be identified within the packages and compared them across the delivery mechanisms and four quality indicators. Results Each implementation package included at least 27 out of 30 potentially applicable BCTs representing 15 of 16 BCT categories. Whilst 23 BCTs were shared across all four implementation packages (e.g. BCTs relating to feedback and comparing behaviour), some BCTs were unique to certain delivery mechanisms (e.g. ‘graded tasks’ and ‘problem solving’ for educational outreach). BCTs addressing the determinants ‘environmental context’ and ‘social and professional roles’ (e.g. ‘restructuring the social and ‘physical environment’ and ‘adding objects to the environment’) were indicator specific. We found it challenging to operationalise BCTs targeting ‘environmental context’, ‘social influences’ and ‘social and professional roles’ within our chosen delivery mechanisms. Conclusion We have demonstrated a transparent process for selecting, operationalising and verifying the BCT content in implementation packages adapted to target four quality indicators in primary care. There was considerable overlap in BCTs identified across the four indicators suggesting core BCTs can be embedded and verified within delivery mechanisms commonly available to primary care. Whilst feedback reports can include a wide range of BCTs, computerised prompts can deliver BCTs at the time of decision making, and educational outreach can allow for flexibility and individual tailoring in delivery. Electronic supplementary material The online version of this article (10.1186/s13012-017-0704-7) contains supplementary material, which is available to authorized users.

Objective: To explore factors that influence decision-making in relation to prenatal diagnostic testing (PDT) for inherited retinal disease (IRD). Method: Semi-structured interviews were conducted with 50 adults with IRD, selected from a larger sample to provide a diversity of backgrounds and opinions on genetic testing. Interviews were transcribed verbatim and analysed using thematic analysis. Results: Mostly participants supported PDT, believing that it would provide information to help them prepare for and plan the future care of the child and the potential for early access to emerging therapies. Opposition to PDT stemmed from its use to justify termination of pregnancy, with participants feeling that it was not justified as they retained a good quality of life despite their visual impairment. Participants raised concerns about the risk of PDT and the accuracy of the results. However, most suggested that it should be available as an option for others, but for specific reasons and not as a part of routine care. Conclusion: The variation in attitudes towards PDT and uncertainty about the risk and accuracy of results suggest that individuals at risk of having a child with IRD should have access to genetic counselling to support decision making.

Aims/Hypothesis: The aim of this research was to explore the relationship between incident epilepsy and type 1 diabetes in British participants. Methods: Using The Health Improvement Network database, we conducted a retrospective, open-cohort study. Patients who were newly diagnosed with type 1 diabetes mellitus at the age of ≤40 years were identified and followed-up from 1 January 1990 to 15 September 2015. These patients, identified as not suffering from epilepsy at the time of diagnosis, were randomly matched with up to four individuals without type 1 diabetes mellitus, based on age, sex and participating general practice. A Cox regression analysis was subsequently performed using Townsend deprivation index, cerebral palsy, head injury and learning disabilities as model covariates. Results: The study population consisted of a total of 24,610 individuals (4922 with type 1 diabetes and 19,688 controls). These individuals were followed up for a mean of 5.4 years (approximately 132,000 person-years of follow up). Patients with type 1 diabetes were significantly more likely to be diagnosed with epilepsy during the observation period compared with controls (crude HR [95% CI]: 3.02 [1.95, 4.69]). The incidence rate was estimated to be 132 and 44 per 100,000 person-years in patients and controls, respectively. This finding persisted after adjusting for model covariates (adjusted HR [95% CI]: 3.01 [1.93, 4.68]) and was also robust to sensitivity analysis, excluding adult-onset type 1 diabetes mellitus. Conclusions/Interpretation: Patients with type 1 diabetes are at approximately three-times greater risk of developing epilepsy compared with matched controls without type 1 diabetes. This should be considered when investigating seizure-related disorders in patients with type 1 diabetes mellitus. © 2016, The Author(s).

Background: Diagnostic tests are often evaluated according to how the results will change clinical management. Patients may value information even if the management does not change. Objective: To investigate the willingness of adults with inherited retinal disease to undergo and pay for diagnostic genetic testing in three hypothetical scenarios and to explore the factors that influence decision making. Methods: Fifty patients were purposively sampled from an initial cohort of 200 participants and presented with three scenarios whereby genetic testing provided increasing information: (i) confirming the diagnosis and inheritance pattern alone, (ii) providing additional information on future visual function, and (iii) identifying in addition a new treatment which could stabilise their condition. Willingness-to-pay (WTP) was elicited using an iterative bidding game. Regression analysis was used to investigate the probability of agreeing to and paying for testing. Qualitative data were also reviewed to provide a comprehensive understanding of WTP and decision making. Results: The majority of participants agreed to undergo genetic testing in each of the three scenarios. Scenario 2 was the least acceptable with 78% of participants agreeing to genetic testing. The probability of agreeing genetic testing decreased with age. Between 72%-96% of participants reported a WTP for genetic testing. Average WTP was £539, £1,516 and £6,895 for scenarios 1, 2 and 3 respectively. WTP appeared to rise with age and income. Qualitative data provided additional detail about the rationale behind participants’ decisions. Conclusions: The study suggests that patients with inherited retinal disease were willing to undergo and to pay for diagnostic genetic testing, suggesting that they valued the information it may provide. However, several patients preferred not to receive prognostic information and were less willing to pay for genetic testing that yielded such detail.

Advances in sequencing technology and the movement of genetic testing into all areas of medicine will increase opportunities for molecular confirmation of a clinical diagnosis. For health-care professionals without formal genetics training, there is a need to know what patients understand about genetics and genetic testing and their information needs and preferences for the disclosure of genetic testing results. These topics were explored during face-to-face interviews with 50 adults with inherited retinal disease, selected in order to provide a diversity of opinions. Participants had variable understanding of genetics and genetic testing, including basic concepts such as inheritance patterns and the risk to dependents, and many did not understand the term ‘genetic counselling'. Most were keen for extra information on the risk to others, the process for genetic testing and how to share the information with other family members. Participants were divided as to whether genetic testing should be offered at the time of the initial diagnosis or later. Many would prefer the results to be given by face-to-face consultation, supplemented by further information in a format accessible to those with visual impairment. Health-care professionals and either leaflets or websites of trusted agencies were the preferred sources of information. Permission should be sought for disclosure of genetic information to other family members. The information needs of many patients with inherited retinal disease appear to be unmet. An understanding of their information needs and preferences is required to help health-care professionals provide optimal services that meet patient expectations.

Summary Background: One-quarter of children in England are overweight/obese at school entry. We investigated the impact of a programme designed to provide parents of infants and preschool children with the skills required for a healthier family lifestyle. Method: A cohort of families was followed across the 8-week HENRY (Health Exercise Nutrition for the Really Young) parent course at nine locations in England. Seventy-seven parents enrolled on the course, of which 71 agreed to complete questionnaires addressing eating behaviours, dietary intake and parental self-efficacy. Pre- and post-course data was available from 60 (84.5%) parents (8-week follow-up data from 58 parents) and was analysed using repeated measures analyses. Results: Significant changes were observed, with most sustained at follow-up. Parents reported increased self-efficacy and ability to encourage good behaviour (P < 0.001). Increased consumption of fruits and vegetables was reported in both children and adults, together with reduced consumption of sweets, cakes and fizzy drinks in adults (all P < 0.01). There were also positive changes in eating behaviours (e.g. frequency of family mealtimes and eating while watching television or in response to negative emotion [P < 0.01] ) and reduced screen time in adults (P < 0.001). Discussion: The results build upon earlier evaluation, indicating that the HENRY intervention has a beneficial impact upon the families of infants and preschool children. Furthermore, the findings suggest that positive changes inspired by the programme can be maintained beyond its completion. Such changes may serve to protect against later obesity.

Background/aims The views of people with inherited retinal disease are important to help develop health policy and plan services. This study aimed to record levels of understanding of and attitudes to genetic testing for inherited retinal disease, and views on the availability of testing. Methods Telephone questionnaires comprising quantitative and qualitative items were completed with adults with inherited retinal disease. Participants were recruited via postal invitation (response rate 48%), approach at clinic or newsletters of relevant charitable organisations. Results Questionnaires were completed with 200 participants. Responses indicated that participants’ perceived understanding of genetic testing for inherited retinal disease was variable. The majority (90%) considered testing to be good/very good and would be likely to undergo genetic testing (90%) if offered. Most supported the provision of diagnostic (97%) and predictive (92%) testing, but support was less strong for testing as part of reproductive planning. Most (87%) agreed with the statement that testing should be offered only after the individual has received genetic counselling from a professional. Subgroup analyses revealed differences associated with participant age, gender, education level and ethnicity (p

Catastrophizing about sleeplessness has been investigated in adults and children, but little is known about adolescents. This article aimed to (a) investigate whether early adolescent girls catastrophized about consequences of sleeplessness, (b) describe topics in catastrophizing sequences, (c) examine the association between sleep quality and catastrophizing, and (d) assess whether puberty moderated this association. Girls (n = 115) between 11 and 12 years old completed adapted versions of the Pittsburgh Sleep Quality Index, the Pubertal Developmental Scale, and the Catastrophizing Interview. Twenty-four (21%) participants produced catastrophizing sequences, including concerns about school and mood. Sleep quality was associated with catastrophizing (β = 0.19, p = .042); however, puberty did not moderate this association (β = 0.15, p = .126). Findings highlight the importance of sleep-related cognitions in adolescent girls.