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Many metamorphic rocks have a fabric. What is often not clear is how much deformational or metamorphic processes contributed to the formation of these fabrics. Are foliations always the result of strain? When does intrinsic crystallographic anisotropy alone lead to the formation of structural elements? Understanding the relative contributions of deformation and metamorphism in rock fabrics is fundamentally important because it is foundational to understanding the role of stress in reacting and deforming rocks.To this end, we make a major advance in our understanding of fabric development in reacting rocks by showing in time-resolved (4D) synchrotron microtomography (µCT) experiments that when a gypsum dehydration reaction occurs in a differentially stressed sample the reaction products develop orthogonally to the largest principal stress. This is an important finding because we can show with our µCT data that this preferred orientation forms early in the reaction and at very small strains (

Purpose: Opioids are one of the high-risk medication classes that are administered to critically ill patients during their intensive care unit (ICU) stay. However, little attention has been given to inpatient opioid prescribing practices, especially in critically ill patients. The purpose of our study was to characterize opioid prescribing practices across 2 transitions of care during an inpatient hospital stay: medical ICU (MICU)/intermediate care unit (IMC) to floor and floor to hospital discharge and identify potential patient-specific factors that impact opioid continuation. Methods: This is a retrospective cohort study evaluating opioid-naive adult patients with new opioid therapy initiated in MICU/IMC at a tertiary care academic medical center from December 1, 2016, to November 30, 2017. Opioid continuation rate was assessed twice: transition 1 (MICU/IMC to floor) and transition 2 (floor to hospital discharge). Results: In total, 112 opioid-naive patients with initial opioid administration in the MICU/IMC were included. Opioid therapy was continued in 56.1% (37/66) at transition 1 and 56.8% of patients (21/37) at transition 2. Patients with opioids continued at transition 1 had a longer hospital length of stay compared to those not continued on opioids, 22 (interquartile range [IQR] 11-36) vs 8 (IQR 6-14; P = .0004). Among the patients continued on opioids at hospital discharge, intubation during hospital stay and cumulative opioid dosage were greater than those not continued on opioids (17 [80.9%] vs 7 [43.8%], P = .019; and 3482 mcg [IQR 1690-9530] vs 732.5 mcg [IQR 187.5-1360.9], P = .0018, respectively). Conclusions: Opioid-naive patients receiving opioid therapy in the MICU/IMC had a continuation rate of >56% during transitions of care, including hospital discharge. Factors that contributed to the continuation of opioids at transitions of care included longer hospital length of stay, intubation, and cumulative hospital opioid dosage. These findings may help to provide health systems with guidance on targeted opioid stewardship programs.

ObjectivesAntiepileptic and antiarrhythmic drugs inhibit voltage-gated sodium (Na+) channels (VGSCs), and preclinical studies show that these medications reduce tumour growth, invasion and metastasis. We investigated the association between VGSC inhibitor use and survival in breast, bowel and prostate cancer patients.DesignRetrospective cohort study.SettingIndividual electronic primary healthcare records extracted from the Clinical Practice Research Datalink (CPRD).ParticipantsRecords for 132,996 patients with a diagnosis of breast, bowel or prostate cancer.Primary and secondary outcome measuresAdjusted Cox proportional hazards regression was used to analyse cancer-specific survival associated with exposure to VGSC inhibitors. Exposure to non-VGSC-inhibiting antiepileptic medication and other non-VGSC blockers were also considered. Drug exposure was treated as a time-varying covariate to account for immortal time bias.ResultsDuring 1,002,225 person-years of follow-up, there were 42,037 cancer-specific deaths. 53,724 (40.4%) cancer patients had at least one prescription for a VGSC inhibitor of interest. Increased risk of cancer-specific mortality was associated with exposure to this group of drugs (HR 1.59, 95% CI 1.56-1.63, pConclusionsAssociation between VGSC inhibitor use and mortality in cancer patients varies according to indication. Exposure to VGSC-inhibiting antiarrhythmics, but not anticonvulsants, supports findings from preclinical data, with improved survival. However, additional confounding factors may underlie these associations, highlighting the need for further study.Strengths and limitations of this studyPrimary care research data with large sample size and statistical power.No direct information on metastasis as an outcome.Drug exposure data are based on prescriptions.Drug exposure is treated as a time-varying covariate to account for immortal time bias.

Material extrusion additive manufacturing (MEAM) and other additive manufacturing methods provide part design options that would be difficult or impossible to realize with conventional manufacturing methods. However, the mechanical properties of parts produced with MEAM are lower than bulk material properties because of the interfaces between roads and layers inherent to the additive build technique of MEAM. In addition, the success of the MEAM process and the resulting part quality depend on the proper selection of the many settings and variables present in MEAM. The effects of material dependent MEAM process parameters on the interlayer bonding and percent crystallinity of MEAM parts fabricated with polyphenylene sulfide (PPS) were examined in this study using a design of experiments technique known as the Taguchi method. The MEAM parameters studied were print temperature, heat-treatment time, and heat-treatment temperature. MEAM parts were tested perpendicular to the layers in order to characterize the interlayer bonding. Heat-treatment temperature was shown to be the most influential parameter on all the studied properties. Utilizing heat-treatments on MEAM parts increased the ultimate tensile strength (UTS) from 52% of the PPS film UTS to 80%. Similar increases were seen in the Young’s modulus, from 57% of the PPS film Young’s modulus to 72%. The study showed that utilizing post-processing heat-treatments on MEAM parts could improve the interlayer bonding in these parts. The use of these heat-treatments could be applied to other materials in order to increase the use of MEAM parts in end use applications.

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.

Digital, multimedia information resources (MMIs) containing text, video, animation and pictures are a promising alternative to written participant information materials designed to inform children, adolescents and parents about healthcare trials, but little research has tested whether they are fit for purpose. This study employed a consecutive groups design and user testing questionnaire to assess whether participants were able to find and understand key information in multimedia resources. Two rounds of testing were completed. In each round, seven children aged 7–11 tested the MMI with a parent; six adolescents aged 12–17 and seven parents tested the MMI independently. After round 1, the resources were revised based on participant scores, behaviour and feedback. Round 1 identified problems with 2/10 information items (length of trial and use of insulin pump); only 3/20 participants could locate all information items without difficulty. After revisions, 14/20 participants scored a clear round. Information comprehension was high: 96% understood in round 1 and 99% in round 2. Participant feedback on the multimedia resources was positive, although presentation preferences varied. User testing was employed successfully with children, adolescents and parents to identify issues with, and improve, multimedia resources developed to inform potential healthcare trial participants.

BackgroundPatient safety measurement remains a global challenge. Patients are an important but neglected source of learning; however, little is known about what patients can add to our understanding of safety. We sought to understand the incidence and nature of patient-reported safety concerns in hospital.MethodsFeedback about the experience of safety within hospital was gathered from 2471 inpatients as part of a multicentre, waitlist cluster randomised controlled trial of an intervention, undertaken within 33 wards across three English NHS Trusts, between May 2013 and September 2014. Patient volunteers, supported by researchers, developed a classification framework of patient-reported safety concerns from a random sample of 231 reports. All reports were then classified using the patient-developed categories. Following this, all patient-reported safety concerns underwent a two-stage clinical review process for identification of patient safety incidents.ResultsOf the 2471 inpatients recruited, 579 provided 1155 patient-reported incident reports. 14 categories were developed for classification of reports, with communication the most frequently occurring (22%), followed by staffing issues (13%) and problems with the care environment (12%). 406 of the total 1155 patient incident reports (35%) were classified by clinicians as a patient safety incident according to the standard definition. 1 in 10 patients (264 patients) identified a patient safety incident, with medication errors the most frequently reported incident.ConclusionsOur findings suggest that patients can provide insight about safety that complements existing patient safety measurement, with a frequency of reported patient safety incidents that is similar to those obtained via case note review. However, patients provide a unique perspective about hospital safety which differs from and adds to current definitions of patient safety incidents.Trial registration numberISRCTN07689702; pre-results.

Objective To evaluate the efficacy of the Patient Reporting and Action for a Safe Environment intervention. Design A multicentre cluster randomised controlled trial. Setting Clusters were 33 hospital wards within five hospitals in the UK. Participants All patients able to give informed consent were eligible to take part. Wards were allocated to the intervention or control condition. Intervention The ward-level intervention comprised two tools: (1) a questionnaire that asked patients about factors contributing to safety (patient measure of safety (PMOS)) and (2) a proforma for patients to report both safety concerns and positive experiences (patient incident reporting tool). Feedback was considered in multidisciplinary action planning meetings. Measurements Primary outcomes were routinely collected ward-level harm-free care (HFC) scores and patient-level feedback on safety (PMOS). Results Intervention uptake and retention of wards was 100% and patient participation was high (86%). We found no significant effect of the intervention on any outcomes at 6 or 12 months. However, for new harms (ie, those for which the wards were directly accountable) intervention wards did show greater, though non-significant, improvement compared with control wards. Analyses also indicated that improvements were largest for wards that showed the greatest compliance with the intervention. Limitations Adherence to the intervention, particularly the implementation of action plans, was poor. Patient safety outcomes may represent too blunt a measure. Conclusions Patients are willing to provide feedback about the safety of their care. However, we were unable to demonstrate any overall effect of this intervention on either measure of patient safety and therefore cannot recommend this intervention for wider uptake. Findings indicate promise for increasing HFC where wards implement ≥75% of the intervention components. Trial registration number ISRCTN07689702; pre-results.

Background Randomised controlled trials are considered the best method for determining the effectiveness and safety of health interventions. Trials involving children are essential to ensure that treatments are safe and effective. However, many trials, in both adult and paediatric populations, do not achieve recruitment targets and/or maintain retention of participants, which can lead to a reduction in the internal and external validity of the results. Identifying ways of improving trial efficiency are important in order to increase the successful completion of trials. Main body A ‘Study Within A Trial’ (SWAT) is a self-contained study embedded within an ongoing trial, which aims to establish evidence to improve the management and delivery of trials in healthcare. Increasing numbers of SWATs have been undertaken in recent years yet very few within paediatric trials. Herein, we describe some of the challenges with undertaking a programme of SWATs within paediatric clinical trials in the UK. The TRECA (TRials Engagement in Children and Adolescents) study involves developing multimedia websites for use within paediatric trials to provide recruitment information to children, young people and their families about the clinical trial. Challenges encountered included governance issues such as host trial approval processes and sharing of anonymised data, funding issues for host trials, internet quality and accessibility within the healthcare setting, and ethical concerns associated with SWAT methodology. We believe the ethical concerns are more pronounced in the paediatric setting, perhaps because of the fewer SWATs undertaken in these settings or that a more cautious, risk-averse approach to undertaking research with children is taken. Conclusion SWATs are becoming increasingly common to provide an evidence base for methods to improve trial efficiency. However, we encountered a number of unanticipated challenges to embedding TRECA that have not been previously reported within the scientific literature. We believe that, if these issues were addressed through wider promotion and explanation of undertaking SWATs involving all key stakeholders, as well as by exploration of alternative funding models for SWATs, this would enable more streamlined, appropriate and timely processes for SWATs and a stronger evidence base for what works to increase trial efficiency. Trial registration The TRECA study is registered on ISRCTN, ID 73136092. Registered on 24 August 2016.

BackgroundEstimates suggest that, in NHS hospitals, incidents causing harm to patients occur in 10% of admissions, with costs to the NHS of > £2B. About one-third of harmful events are believed to be preventable. Strategies to reduce patient safety incidents (PSIs) have mostly focused on changing systems of care and professional behaviour, with the role that patients can play in enhancing the safety of care being relatively unexplored. However, although the role and effectiveness of patient involvement in safety initiatives is unclear, previous work has identified a general willingness among patients to contribute to initiatives to improve health-care safety.AimOur aim in this programme was to design, develop and evaluate four innovative approaches to engage patients in preventing PSIs: assessing risk, reporting incidents, direct engagement in preventing harm and education and training.Methods and resultsWe developed tools to report PSIs [patient incident reporting tool (PIRT)] and provide feedback on factors that might contribute to PSIs in the future [Patient Measure of Safety (PMOS)]. These were combined into a single instrument and evaluated in the Patient Reporting and Action for a Safe Environment (PRASE) intervention using a randomised design. Although take-up of the intervention by, and retention of, participating hospital wards was 100% and patient participation was high at 86%, compliance with the intervention, particularly the implementation of action plans, was poor. We found no significant effect of the intervention on outcomes at 6 or 12 months. The ThinkSAFE project involved the development and evaluation of an intervention to support patients to directly engage with health-care staff to enhance their safety through strategies such as checking their care and speaking up to staff if they had any concerns. The piloting of ThinkSAFE showed that the approach is feasible and acceptable to users and may have the potential to improve patient safety. We also developed a patient safety training programme for junior doctors based on patients who had experienced PSIs recounting their own stories. This approach was compared with traditional methods of patient safety teaching in a randomised controlled trial. The study showed that delivering patient safety training based on patient narratives is feasible and had an effect on emotional engagement and learning about communication. However, there was no effect on changing general attitudes to safety compared with the control.ConclusionThis research programme has developed a number of novel interventions to engage patients in preventing PSIs and protecting them against unintended harm. In our evaluations of these interventions we have been unable to demonstrate any improvement in patient safety although this conclusion comes with a number of caveats, mainly about the difficulty of measuring patient safety outcomes. Reflecting this difficulty, one of our recommendations for future research is to develop reliable and valid measures to help efficiently evaluate safety improvement interventions. The programme found patients to be willing to codesign, coproduce and participate in initiatives to prevent PSIs and the approaches used were feasible and acceptable. These factors together with recent calls to strengthen the patient voice in health care could suggest that the tools and interventions from this programme would benefit from further development and evaluation.Trial registrationCurrent Controlled Trials ISRCTN07689702.FundingThe National Institute for Health Research Programme Grants for Applied Research programme.

Background: There is scope for additional research into the specific linguistic and sequential structures used in speech and language therapist (SLT)-led therapeutic conversations with people with aphasia (PWA). Whilst there is some evidence that SLTs use different conversational strategies than the partners of PWA, research to date has focussed mainly on measuring the effects of conversation-based therapies—not on analysing therapeutic conversations taking place between SLTs and PWA.\ud \ud Aims: This paper presents an analysis of the use of oh-prefacing by some PWA during therapeutic supported conversations with SLTs.\ud \ud Methods & Procedures: Normally occurring therapeutic conversations between SLTs and PWA after stroke were qualitatively analysed using Conversation Analysis. Interactions with five PWA were video-recorded, involving three different specialist stroke SLTs.\ud \ud Outcomes & Results: The analysis revealed a difference in the way some PWA use turns that display understanding (e.g., oh right) versus those that continue the conversation, merely claiming understanding (e.g., right). This use of oh-prefacing is similar to that described in the literature on typical conversations. In our data, SLTs are shown to treat oh-prefaced turns differently from non-oh-prefaced turns, by pursuing the topic in the latter, and progressing on to a new topic in the former.\ud \ud Conclusions: At least some PWA use oh-prefacing in the same way as non-language-impaired adults to display understanding of information versus merely claiming to understand. The SLTs in our data are shown to treat non-oh-prefaced turns as mere claims of understanding by providing the PWA with additional information, using supported conversation techniques, and pursuing additional same-topic talk, whereas oh-prefaced turns are treated as displays of understanding by being confirmed, and leading to changes of topic. This study is a first step in providing SLTs with a clearer understanding of the ways in which they are assessing the understanding of PWA, which may in turn help them better support non-therapy staff.

Vancomycin, a glycopeptide antimicrobial, is commonly employed for empirical and definitive treatment of infections due to resistant gram-positive pathogens, notably methicillin-resistant Staphylococcus aureus (MRSA). Given wide interpatient and intrapatient pharmacokinetic variability coupled with

BackgroundEnsuring patient safety is vital in primary care. One mechanism to increase patient safety is through a practice known as safety netting. Safety netting is widely recommended in national guidelines; however, a variety of definitions exist with no consensus on when safety netting should be used and what advice or actions it should contain.AimThis study aimed to identify different definitions of safety netting to provide conceptual clarity and propose a common approach to safety netting in primary care.Design and settingLiterature review and evidence synthesis of international articles relating to safety netting in primary care.MethodAn electronic database and grey-literature search was conducted using terms around the theme of safety netting with broad inclusion criteria.ResultsA total of 47 studies were included in the review. Safety netting was defined as a consultation technique to communicate uncertainty, provide patient information on red-flag symptoms, and plan for future appointments to ensure timely re-assessment of a patient’s condition. Safety-netting advice may include information on the natural history of the illness, advice on worrying symptoms to look out for, and specific information on how and when to seek help. In addition to advice within the consultation, safety netting includes follow-up of investigations and hospital referrals. Safety netting was considered to be particularly important when consulting with children, the acutely unwell, patients with multimorbidity, and those with mental health problems.ConclusionSafety netting is more than solely the communication of uncertainty within a consultation. It should include plans for follow-up as well as important administrative aspects, such as the communication of test results and management of hospital letters.

Background Primary care physicians are particularly prone to high levels of burnout and poor well-being. Despite this, no qualitative studies have specifically investigated the best ways to improve well-being and prevent burnout in primary care physicians. Previous interventions within primary care have been person-oriented and mainly focused on mindfulness, but there has been no prior research on whether general practitioners (GPs) deem this to be the best approach. Objectives To explore strategies that could improve GP well-being and reduce or prevent burnout, based on GP perceptions of the workplace factors that affect their levels of well-being and burnout. Methods Five focus groups were conducted, with 25 GPs (locums, salaried, trainees, and partners) in the UK, between September 2015 and February 2016. Focus groups took place in GP practices and private meeting rooms. Discussions were centered on the workplace factors that they perceived to influence their well-being, along with strategies that they use either personally, or as a practice, to try and prevent burnout. Furthermore, strategies that could feasibly be implemented by individuals and practices to improve well-being, as well as changes that are needed by groups or organizations that are external to their practice (e.g., the government) to improve the working conditions, were explored. Thematic analysis was conducted on the transcripts. Results Based on the contributors to burnout and workplace well-being that the participants identified, the following feasible strategies were suggested: compulsory daily coffee breaks, increasing self- and organizational awareness of the risks of burnout and mentoring or buddy systems. System-level organizational changes were voiced as vital, however, to improve the well-being of all primary care physicians. Increasing resources seemed to be the ideal solution, to allow for more administrative staff and GPs. Conclusion These strategies merit further consideration by researchers, physicians, healthcare organizations and policy makers both in the UK and beyond. Failure to do so may result in healthcare staff becoming even more burntout, potentially leading to a loss of doctors from the workforce.

Objectives To compare a new co-designed, patient incident reporting tool with three established methods of detecting patient safety incidents and identify if the same incidents are recorded across methods. Method Trained research staff collected data from inpatients in nine wards in one university teaching hospital during their stay. Those classified as patient safety incidents were retained. We then searched for patient safety incidents in the corresponding patient case notes, staff incident reports and reports to the Patient Advice and Liaison Service specific to the study wards. Results In the nine wards, 329 patients were recruited to the study, of which 77 provided 155 patient reports. From these, 68 patient safety incidents were identified. Eight of these were also identified from case note review, five were also identified in incident reports, and two were also found in the records of a local Patient Advice and Liaison Service. Reports of patients covered a range of events from their immediate environment, involving different health professionals and spanning the entire spectrum of care. Conclusion Patient safety incidents reported by patients are unlikely to be found through other established methods of incident detection. When hospitalized patients are asked about their care, they can provide a unique perspective on patient safety. Co-designed, real-time reporting could be a helpful addition to existing methods of gathering patient safety intelligence.

In this study, phenolic compounds were analyzed in developing berries of four Canadian grown sea buckthorn (Hippophae rhamnoides L.) cultivars ('RC-4', 'E6590', 'Chuyskaya' and 'Golden Rain') and in leaves of two of these cultivars. Among phenolic acids, p-coumaric acid was the highest in berries, while gallic acid was predominant in leaves. In the flavonoid class of compounds, myricetin/rutin, kaempferol, quercetin and isorhamnetin were detected in berries and leaves. Berries of the 'RC-4' cultivar had approximately ⩾ 2-fold higher levels of myricetin and quercetin at 17.5mg and 17.2 mg/100 g FW, respectively, than the other cultivars. The flavonoid content in leaves was considerably more than in berries with rutin and quercetin levels up to 135 mg and 105 mg/100 g FW, respectively. Orthologs of 15 flavonoid biosynthesis pathway genes were identified within the transcriptome of sea buckthorn mature seeds. Semi-quantitative RT-PCR analysis of these genes in developing berries indicated relatively higher expression of genes such as CHS, F3'H, DFR and LDOX in the 'RC-4' cultivar than in the 'Chuyskaya' cultivar. Vitamin C levels in ripened berries of the Canadian cultivars were on the high end of the concentration range reported for most other sea buckthorn cultivars. Orthologs of genes involved in vitamins C and E biosynthesis were also identified, expanding the genomic resources for this nutritionally important plant.

Discussion of unanticipated problems in care with patients and their families (‘open disclosure’) is now widely advocated. Despite international efforts and the introduction of a range of policies and guidance to promote such discussions, the expectations of policy makers and patients are often not matched in practice. We consider some reasons for the persistence of shortfalls in the occurrence and quality of open disclosure. We draw on research conducted to investigate the implementation of a ‘ Being open’ policy in England, reflecting particularly on insights derived from interviews with health care professionals. Health care professionals were broadly supportive of the idea of open disclosure. Some expressed well-recognized concern about punishment and being blamed, but this did not appear to be the main driver of their communication practices. Their accounts of what happened around particular problems in health care indicated that they brought a complex range of considerations to bear on questions of whether and how these were discussed with patients and relatives. Guidance about open disclosure based on assessments of levels of harm to patients can complicate and perhaps distort health care professionals’ approaches, particularly when the extent and/or cause of harm was uncertain. Health care professionals who engage in open disclosure must be able to negotiate appropriate ways through complex and sensitive discussions. The responses of patients and relatives are not always predictable and even the best open disclosure practice may not resolve problems and concerns. Guidance, training and support for staff need to reflect these challenges.

Objectives The aims of the study were (1) to explore whether primary care physicians (general practitioners [GPs]) perceive burnout and well-being to impact on the quality and safety of patient care and (2) to determine potential mechanisms behind these associations. Method Five focus groups with 25 practicing GPs were conducted in England, either in the participants’ practice or in a private meeting room outside of their workplace. An interview schedule with prompts was followed with questions asking how participants perceive GP burnout and poor well-being could impact on patient care delivery. Audio recordings were transcribed verbatim and analyzed using thematic analysis. Results General practitioners believed that poor well-being and burnout affect the quality of care patients receive through reducing doctors’ abilities to empathize, to display positive attitudes and listening skills, and by increasing the number of inappropriate referrals made. Participants also voiced that burnout and poor well-being can have negative consequences for patient safety, through a variety of mechanisms including reduced cognitive functioning and decision-making abilities, a lack of headspace, and fatigue. Furthermore, it was suggested that the relationship between well-being/burnout and mistakes is likely to be circular. Conclusions Further research is needed to ascertain the validity of these perceptions. If found, physicians, healthcare organizations, and policy makers should examine how they can improve physician well-being and prevent burnout, because this may be a route to ensure high-quality and safe patient care.

Objective To identify and examine tensions and uncertainties in person-centred approaches to self-management support – approaches that take patients seriously as moral agents and orient support to enable them to live (and die) well on their own terms. Methods Interviews with 26 UK clinicians about working with people with diabetes or Parkinson’s disease, conducted within a broader interdisciplinary project on self-management support. The analysis reported here was informed by philosophical reasoning and discussions with stakeholders. Results Person-centred approaches require clinicians to balance tensions between the many things that can matter in life, and their own and each patient’s perspectives on these. Clinicians must ensure that their supportive efforts do not inadvertently disempower people. When attending to someone’s particular circumstances and perspectives, they sometimes face intractable uncertainties, including about what is most important to the person and what, realistically, the person can or could do and achieve. The kinds of professional judgement that person-centred working necessitates are not always acknowledged and supported. Conclusion Practical and ethical tensions are inherent in person-centred support and need to be better understood and addressed. Practice implications Professional development and service improvement initiatives should recognise these tensions and uncertainties and support clinicians to navigate them well.

Background Support for self-management (SSM) is a prominent strand of health policy internationally, particularly for primary care. It is often discussed and evaluated in terms of patients’ knowledge, skills and confidence, health-related behaviours, disease control or risk reduction, and service use and costs. However, these goals are limited, both as guides to professional practice and as indicators of its quality. In order to better understand what it means to support self-management well, we examined health professionals’ views of success in their work with people with long-term conditions. This study formed part of a broader project to develop a conceptual account of SSM that can reflect and promote good practice. Methods Semi-structured individual interviews (n = 26) and subsequent group discussions (n = 5 groups, 30 participants) with diverse health professionals working with people with diabetes and/or Parkinson’s disease in NHS services in London, northern England or Scotland. The interviews explored examples of more and less successful work, ways of defining success, and ideas about what facilitates success in practice. Subsequent group discussions considered the practical implications of different accounts of SSM. Interviews and group discussions were audio-recorded, transcribed and analysed thematically. Results Participants identified a wide range of interlinked aspects or elements of success relating to: health, wellbeing and quality of life; how well people (can) manage; and professional-patient relationships. They also mentioned a number of considerations that have important implications for assessing the quality of their own performance. These considerations in part reflect variations in what matters and what is realistically achievable for particular people, in particular situations and at particular times, as well as the complexity of questions of attribution. Conclusions A nuanced assessment of the quality of support for self-management requires attention to the responsiveness of professional practice to a wide, complex range of personal and situational states, as well as actions and interactions over time. A narrow focus on particular indicators can lead to insensitive or even perverse judgements and perhaps counterproductive effects. More open, critical discussions about both success and the assessment of quality are needed to facilitate good professional practice and service improvement initiatives. Electronic supplementary material The online version of this article (doi:10.1186/s12875-017-0611-7) contains supplementary material, which is available to authorized users.

BackgroundThe Health and Social Care Act mandated research use as a core consideration ofhealth service commissioning arrangements in England. We undertook a controlled before and after study to evaluate whether access to a demand-led evidence briefing service improved use of research evidence by commissioners compared with less intensive and less targeted alternatives.MethodsNine Clinical Commissioning Groups (CCGs) in the North of England received one of three interventions: A) access to an evidence briefing service; B) contact plus an unsolicited push of non-tailored evidence; or C) unsolicited push of non-tailored evidence. Data for the primary outcome measure were collected at baseline and 12 months using a survey instrument devised to assess an organisations' ability to acquire, assess, adapt and apply research evidence to support decision-making.Documentary and observational evidence of the use of the outputs of the service were sought and interviews with CCG participants were undertaken.ResultsOver the course of the study the service addressed 24 topics raised by participating CCGs. At 12 months, the evidence briefing service was not associated with increases in CCG capacity to acquire, assess, adapt and apply research evidence to support decision making, individual intentions to use research findings or perceptions of CCG relationships with researchers. Regardless of intervention received, participating CCGs indicated that they remained inconsistent in their research seeking behaviours and in their capacity to acquire research. The informal nature of decision making processes meant that there was little traceability of the use of evidence. Low baseline and followup response rates and missing data limit the reliability of the findings.ConclusionsAccess to a demand-led evidence briefing service did not improve the uptake and use of research evidence by NHS commissioners compared with less intensive and less targeted alternatives. Commissioners appear well intentioned but ad hoc users of research. Further research is required on the effects of interventions and strategies to build individual and organisational capacity to use research.

BackgroundThere has been an increase in the utilisation of acupuncture in recent years, yet the evidence base is insufficiently well established to be certain about its clinical effectiveness and cost-effectiveness. Addressing the questions related to the evidence base will reduce uncertainty and help policy- and decision-makers with regard to whether or not wider access is appropriate and provides value for money.AimOur aim was to establish the most reliable evidence on the clinical effectiveness and cost-effectiveness of acupuncture for chronic pain by drawing on relevant evidence, including recent high-quality trials, and to develop fresh evidence on acupuncture for depression. To extend the evidence base we synthesised the results of published trials using robust systematic review methodology and conducted a randomised controlled trial (RCT) of acupuncture for depression.Methods and resultsWe synthesised the evidence from high-quality trials of acupuncture for chronic pain, consisting of musculoskeletal pain related to the neck and low back, osteoarthritis of the knee, and headache and migraine, involving nearly 18,000 patients. In an individual patient data (IPD) pairwise meta-analysis, acupuncture was significantly better than both sham acupuncture (p p ConclusionWe have provided the most robust evidence from high-quality trials on acupuncture for chronic pain. The synthesis of high-quality IPD found that acupuncture was more effective than both usual care and sham acupuncture. Acupuncture is one of the more clinically effective physical therapies for osteoarthritis and is also cost-effective if only high-quality trials are analysed. When all trials are analysed, TENS is cost-effective. Promising clinical and economic evidence on acupuncture for depression needs to be extended to other contexts and settings. For the conditions we have investigated, the drawing together of evidence on acupuncture from this programme of research has substantially reduced levels of uncertainty. We have identified directions for further research. Our research also provides a valuable basis for considering the potential role of acupuncture as a referral option in health care and enabling providers and policy-makers to make decisions based on robust sources of evidence.Trial registrationCurrent Controlled Trials ISRCTN63787732.FundingThe National Institute for Health Research Programme Grants for Applied Research programme.

Background To explore the benefits, barriers and disadvantages of implementing an electronic record system (ERS). The extent that the system has become ‘normalised’ into routine practice was also explored. Methods Qualitative semi-structured interviews were conducted with 19 members of NHS staff who represented a variety of staff groups (doctors, midwives of different grades, health care assistants) and wards within a maternity unit at a NHS teaching hospital. Interviews were conducted during the first year of the phased implementation of ERS and were analysed thematically. The four mechanisms of Normalisation Process Theory (NPT) (coherence, cognitive participation, collective action and reflexive monitoring) were adapted for use within the study and provided a theoretical framework to interpret the study’s findings. Results Coherence (participants’ understanding of why the ERS has been implemented) was mixed – whilst those involved in ERS implementation anticipated advantages such as improved access to information; the majority were unclear why the ERS was introduced. Participants’ willingness to engage with and invest time into the ERS (cognitive participation) depended on the amount of training and support they received and their willingness to change from paper to electronic records. Collective action (the extent the ERS was used) may be influenced by whether participants perceived there to be benefits associated with the system. Whilst some individuals reported benefits such as improved legibility of records, others felt benefits were yet to emerge. The parallel use of paper and the lack of integration of electronic systems within and between the trust and other healthcare organisations hindered ERS use. When appraising the ERS (reflexive monitoring) participants perceived the system to negatively impact the patient-clinician relationship, time and patient safety. Conclusions Despite expectations that the ERS would have a number of advantages, its implementation was perceived to have a range of disadvantages and only a limited number of ‘clinical benefits’. The study highlights the complexity of implementing electronic systems and the associated longevity before they can become ‘embedded’ into routine practice. Through the identification of barriers to the employment of electronic systems this process could be streamlined with the avoidance of any potential detriment to clinical services. Electronic supplementary material The online version of this article (doi:10.1186/s12911-016-0406-0) contains supplementary material, which is available to authorized users.

Study design Methodological study nested within a multicentre randomised controlled trial (RCT) of yoga plus usual general practitioner (GP) care vs usual GP care for chronic low back pain. Objective To explore the treatment effects of non-compliance using three approaches in an RCT evaluating yoga for low back pain. Summary of background data A large multicentre RCT using intention-to-treat (ITT) analysis found that participants with chronic low back pain who were offered a 12-week progressive programme of yoga plus usual GP care had better back function than those offered usual GP care alone. However, ITT analysis can underestimate the effect of treatment in those who comply with treatment. As such, the data were analysed using other approaches to assess the problem of non-compliance. The main outcome measure was the self-reported Roland Morris Disability Questionnaire (RMDQ). Methods Complier average causal effect (CACE) analysis, per-protocol analysis and on-treatment analysis were conducted on the data of participants who were fully compliant, predefined as attendance of at least three of the first six sessions and at least three other sessions. The analysis was repeated for participants who had attended at least one yoga session (i.e. any compliance), which included participants who were fully compliant. Each approach was described, including strengths and weaknesses, and the results of the different approaches were compared with those of the ITT analysis. Results For the participants who were fully compliant (n = 93, 60%), a larger beneficial treatment effect was seen using CACE analysis compared with per-protocol, on-treatment and ITT analyses at 3 and 12 months. The difference in mean change in RMDQ score between randomised groups was −3.30 [95% confidence interval (CI) −4.90 to −1.70, P

BackgroundIn 2009 the UK National Patient Safety Agency relaunched its Being Open framework to facilitate the open disclosure of adverse events to patients in the NHS. The implementation of the framework has been, and remains, challenging in practice.AimThe aim of this work was to both critically evaluate and extend the current evidence base relating to open disclosure, with a view to supporting the implementation of a policy of open disclosure of adverse events in the NHS.MethodsThis work was conducted in three phases. The first phase comprised two focused systematic literature reviews, one summarising empirical research on the effectiveness of interventions to enhance open disclosure, and a second, broader scoping review, looking at reports of current opinion and practice and wider knowledge. The second phase involved primary qualitative research with the objective of generating new knowledge about UK-based stakeholders’ views on their role in and experiences of open disclosure. Stakeholder interviews were analysed using the framework approach. The third phase synthesised the findings from the first two phases to inform and develop a set of short pragmatic suggestions for NHS trust management, to facilitate the implementation and evaluation of open disclosure.ResultsA total of 610 papers met the inclusion criteria for the broad review. A large body of literature discussed open disclosure from a number of related, but sometimes conflicted, perspectives. Evidential gaps persist and current practice is based largely on expert consensus rather than evidence. There appears to be a tension between the existing pragmatic guidance and the more in-depth critiques of what being consistent and transparent in health care really means. Eleven papers met the inclusion criteria for the more focused review. There was little evidence for the effectiveness of disclosure alone on organisational or individual outcomes or of interventions to promote and support open disclosure. Interviews with stakeholders identified strong support for the basic principle of being honest with patients or relatives when someone was seriously harmed by health care. In practice however, the issues are complex and there is confusion about a number of issues relating to disclosure policies in the UK. The interviews generated insights into the difficulties perceived within health care at individual and institutional levels, in relation to fully implementing the Being Open guidance.ConclusionsThere are several clear strategies that the NHS could learn from to implement and sustain a policy of openness. Literature reviews and stakeholder accounts both identified the potential benefits of a culture that was generally more open (not just retrospectively open about serious harm). Future work could usefully evaluate the impact of disclosure on legal challenges within the NHS, best practice in models of support and training for open disclosure, embedding disclosure conversations in critical incident analysis and disclosure of less serious events.FundingThe National Institute for Health Research Health Services and Delivery Research programme.

Background Estimates show that as many as one in 10 patients are harmed while receiving hospital care. Previous strategies to improve safety have focused on developing incident reporting systems and changing systems of care and professional behaviour, with little involvement of patients. The need to engage with patients about the quality and safety of their care has never been more evident with recent high profile reviews of poor hospital care all emphasising the need to develop and support better systems for capturing and responding to the patient perspective on their care. Over the past 3 years, our research team have developed, tested and refined the PRASE (Patient Reporting and Action for a Safe Environment) intervention, which gains patient feedback about quality and safety on hospital wards. Methods/design A multi-centre, cluster, wait list design, randomised controlled trial with an embedded qualitative process evaluation. The aim is to assess the efficacy of the PRASE intervention, in achieving patient safety improvements over a 12-month period. The trial will take place across 32 hospital wards in three NHS Hospital Trusts in the North of England. The PRASE intervention comprises two tools: (1) a 44-item questionnaire which asks patients about safety concerns and issues; and (2) a proforma for patients to report (a) any specific patient safety incidents they have been involved in or witnessed and (b) any positive experiences. These two tools then provide data which are fed back to wards in a structured feedback report. Using this report, ward staff are asked to hold action planning meetings (APMs) in order to action plan, then implement their plans in line with the issues raised by patients in order to improve patient safety and the patient experience. The trial will be subjected to a rigorous qualitative process evaluation which will enable interpretation of the trial results. Methods: fieldworker diaries, ethnographic observation of APMs, structured interviews with APM lead and collection of key data about intervention wards. Intervention fidelity will be assessed primarily by adherence to the intervention via scoring based on an adapted framework. Discussion This study will be one of the largest patient safety trials ever conducted, involving 32 hospital wards. The results will further understanding about how patient feedback on the safety of care can be used to improve safety at a ward level. Incorporating the ‘patient voice’ is critical if patient feedback is to be situated as an integral part of patient safety improvements. Trial registration ISRCTN07689702, 16 Aug 2013 Electronic supplementary material The online version of this article (doi:10.1186/1745-6215-15-420) contains supplementary material, which is available to authorized users.

Background: There is an increasing emphasis on the importance of the palliative and end-of-life care being provided in the community. Key to the success of this is the availability of information and educational support to facilitate carers in their role. The aim of the paper is to explore the educational needs of adult carers providing physical and other care to people at the end of life Methods: A qualitative evidence synthesis was conducted using meta-ethnography. Five electronic databases were searched to January 2014, combining terms for: cancer, chronic obstructive pulmonary disease, neurodegenerative conditions, renal disease, heart failure and dementia, with terms for carers and education. Results: A total of 35 papers were included in the review, reporting the experiences of over 900 carers. Throughout the illness trajectory carers were either enabled or hindered in their role by the nature and way information and education were provided. Enabling factors included: a sense of trust in health professionals; timely and accurate information delivered compassionately; access to professionals for information and support particularly during out-of-hours. Where carers experienced a lack of information or support this added to the strain of caring. Carers then felt the need to take on a more active role, acting both as an advocate and decision maker. Conclusions: Carers express information and educational needs throughout the illness trajectory. The quality of health professionals’ communication with carers was fundamental in ensuring carers felt confident and supported. Timely access to information and support from appropriately qualified health professionals should be made available to carers, including the out-of-hours period.

ObjectivesTo understand stakeholders’ views regarding the content and design of paediatric clinical trial multimedia websites. To describe how this knowledge informed the development of the multimedia websites.DesignQualitative study comprising two rounds of interviews or focus groups, with thematic analysis of interview transcripts.ParticipantsSixty-two people (21 children and young people with long-term health conditions, 24 parents and 17 professionals).SettingOne UK children’s hospital and one UK Young Persons’ Advisory Group.ResultsWhen asked what was important in deciding whether to join a trial, children, young people and parents prioritised information about what participation would involve, what the trial was testing, potential benefits and risks of participation and knowing they could leave the trial if they later changed their minds. Young people and parents trusted trial teams to follow regulatory and quality requirements and therefore did not think such information was a priority for the websites, although logos of trusted organisations could lend credibility. Professionals largely concurred with these views. Children and young people advised on the importance of designing the multimedia website to ensure its appearance, tone and wording suited the intended audience and on using animated characters to facilitate children’s engagement.ConclusionsOur study provides insights into the information that families value when deciding about healthcare trial participation. It provides guidance on the design of information resources to appeal to children and young people, while also being acceptable to parents and professionals who are often gatekeepers of children’s access to information. Our findings will be of use to others developing similar multimedia websites. We report specific information needs and new visual preferences that are not usually addressed in printed trial information. Our work illustrates what qualitative research and participatory design practices can contribute to the development of information resources more generally.Trial registration numberISRCTN73136092; Pre-results.