Building trust and increasing inclusion in public health research: co-produced strategies for engaging UK ethnic minority communities in research.

Patient and public involvement and engagement (PPIE) is essential for improved research outcomes and reduced research waste. To be effective, PPIE should provide opportunities for diverse groups to contribute to all research stages. However, UK ethnic minority communities remain underrepresented in research. This article describes strategies adopted in a public health research project that were effective in building trust and increasing inclusion of ethnic minority communities. The study team of researchers and PPIE partners reflects lessons learnt during the project and describe six main strategies that built meaningful levels of trust and inclusion: 1) early start to recruitment of PPIE partners; 2) relationship-focused engagement; 3) co-production and consultation activities; 4) open communication and iterative feedback; 5) co-production of project closure activities, and; 6) diverse research team. Meaningful outcomes for the community included the involvement of people from ethnic minorities as research participants and PPIE partners, community wellbeing, co-production of public health recommendations co-presented at the UK Houses of Parliament, and consortium-wide impact evidenced by the enrolment of 51 active PPIE partners. PPIE partners reflect on their research involvement, offering advice to researchers and encouraging people from ethnic minority communities to take part in research. An important message from PPIE partners is that involvement should not be restricted to projects specific to ethnic minorities but become a routine part of general population research, recognising ethnic minorities as an integral part of UK society. In conclusion, this article demonstrates that with appropriate strategies, inclusion and diversity can be achieved in public health research. We recommend researchers, practitioners and policy makers adopt these strategies when planning their public health projects.

ATP-dependent conformational dynamics in a photoactivated adenylate cyclase revealed by fluorescence spectroscopy and small-angle X-ray scattering.

Structural insights into the photoactivated adenylate cyclases can be used to develop new ways of controlling cellular cyclic adenosine monophosphate (cAMP) levels for optogenetic and other applications. In this work, we use an integrative approach that combines biophysical and structural biology methods to provide insight on the interaction of adenosine triphosphate (ATP) with the dark-adapted state of the photoactivated adenylate cyclase from the cyanobacterium Oscillatoria acuminata (OaPAC). A moderate affinity of the nucleotide for the enzyme was calculated and the thermodynamic parameters of the interaction have been obtained. Stopped-flow fluorescence spectroscopy and small-angle solution scattering have revealed significant conformational changes in the enzyme, presumably in the adenylate cyclase (AC) domain during the allosteric mechanism of ATP binding to OaPAC with small and large-scale movements observed to the best of our knowledge for the first time in the enzyme in solution upon ATP binding. These results are in line with previously reported drastic conformational changes taking place in several class III AC domains upon nucleotide binding.

Evaluation of electropolymerized molecularly imprinted polymers (E-MIPs) on disposable electrodes for detection of SARS-CoV-2 in saliva.

We investigate electropolymerized molecularly imprinted polymers (E-MIPs) for the selective recognition of SARS-CoV-2 whole virus. E-MIPs imprinted with SARS-CoV-2 pseudoparticles (pps) were electrochemically deposited onto screen printed electrodes by reductive electropolymerization, using the water-soluble N-hydroxmethylacrylamide (NHMA) as functional monomer and crosslinked with N,N'-methylenebisacrylamide (MBAm). E-MIPs for SARS-CoV-2 showed selectivity for template SARS-CoV-2 pps, with an imprinting factor of 3:1, and specificity (significance = 0.06) when cross-reacted with other respiratory viruses. E-MIPs detected the presence of SARS-CoV-2 pps in <10 min with a limit of detection of 4.9 log10 pfu/mL, suggesting their suitability for detection of SARS-CoV-2 with minimal sample preparation. Using electrochemical impedance spectroscopy (EIS) and principal component analysis (PCA), the capture of SARS-CoV-2 from real patient saliva samples was also evaluated. Fifteen confirmed COVID-19 positive and nine COVID-19 negative saliva samples were compared against the established loop-mediated isothermal nucleic acid amplification (LAMP) technique used by the UK National Health Service. EIS data demonstrated a PCA discrimination between positive and negative LAMP samples. A threshold real impedance signal (ZRe) ≫ 4000 Ω and a corresponding charge transfer resistance (RCT) ≫ 6000 Ω was indicative of absence of virus (COVID-19 negative) in agreement with values obtained for our control non-imprinted polymer control. A ZRe at or below a threshold value of 600 Ω with a corresponding RCT of <1200 Ω was indicative of a COVID-19 positive sample. The presence of virus was confirmed by treatment of E-MIPs with a SARS-CoV-2 specific monoclonal antibody.

Development of the Manchester framework for the evaluation of emergency department pharmacy services.

BACKGROUND: Many countries, including the United Kingdom, have established Emergency Department (ED) pharmacy services where some ED pharmacists now work as practitioners. They provide both traditional pharmaceutical care and novel practitioner care i.e. clinical examination, yet their impact on quality of care is unknown. AIM: To develop a framework of structures, processes and potential outcome indicators to support evaluation of the quality of ED pharmacy services in future studies. METHOD: Framework components (structures, processes and potential outcome indicators) were identified in three ways: from a narrative review of relevant international literature, and separate panel meetings with ED pharmacists and then other ED healthcare professionals. Structures and processes were collated into categories developed iteratively throughout data collection, with outcome indicators collated into six domains of quality as proposed by the Institute of Medicine. These raw data were then processed e.g. outcome indicators screened for clarity i.e. those which explicitly stated what would be measured were included in the framework. RESULTS: A total of 190 structures, 533 processes, and 503 outcome indicators were identified. Through data processing a total of 153 outcome indicators were included in the final framework divided into the domains safe (32), effective (50), patient centred (18), timely (24), efficient (20) and equitable (9). CONCLUSION: The first framework specific to the quality evaluation ED pharmacy services, service evaluators should validate potential outcome indicators prior to their use. The minimum expected of a high-quality service should also be defined to enable interpretation of relevant measurements.

Social environmental impact of COVID-19 and erectile dysfunction: an explorative review.

BACKGROUND: To date, no attempt has been made to collate literature on the relationship between the social environmental impact of COVID-19 and erectile dysfunction. The aim of this explorative review was to assess and compare the prevalence of erectile dysfunction (ED) in male healthcare workers and males during the COVID-19 pandemic. METHODS: A systematic review of major databases from inception to February 2021 was conducted. Prevalence data were extracted, and a random-effects meta-analysis was undertaken. OUTCOMES: The pooled prevalence of ED amongst healthcare workers working in COVID-19 specific environments, and non-healthcare during the COVID-19 pandemic. RESULTS: Of 52 initial studies, six were included for the final analysis. The pooled prevalence of ED in healthcare workers working in a COVID-19 environment was 63.6% (95% CI 20.3-92.3%), and in non-healthcare workers during the COVID-19 pandemic was 31.9% (95% CI 19.5-47.6%). CONCLUSION: The prevalence of ED in healthcare workers working in COVID-19 environments was higher than representative samples and is of concern. Sexual health (and by extension, overall health), should be a priority when considering ways to care for this population. Considering the social environmental impact of COVID-19 on sexual health and in particular on ED, it is important to provide adequate psychological support systems and to promote quality of life with particular attention to sexual health.

Transitioning into the workforce during the COVID-19 pandemic: Understanding the experiences of student diagnostic radiographers.

INTRODUCTION: The COVID-19 pandemic, with associated pressures on healthcare services and workforce, had implications for final year Diagnostic Radiography students completing their training and transitioning into employment. The aim of this study was to explore their experience as novice practitioners starting work and integrating into the workforce during a time of national crisis. METHODS: Five early career Diagnostic Radiographers, eligible to join the temporary HCPC register, were recruited. One to one interviews were completed online exploring their thoughts, feelings and experiences. Participants had the option of using photographs to aid communication. RESULTS: Interviews were transcribed, emerging themes identified and coded. Four main themes emerged specifically related to the COVID-19 pandemic, (i) perceived challenges associated with joining the workforce, (ii) managing expectations and unexpected outcomes during transition, (iii) adapting to changes in systems and structures, (iv) sense of uncertainty relating to professional identity. The impacts were experienced beyond the work environment into social and personal lives. Participants demonstrated resilience as they adapted to their shifting lives and drew on the support of clinical colleagues and University academics for help. They did report feelings of concern and anxiety. The participants all expressed a sense of feeling valued and supported in their new roles. CONCLUSION: The Pandemic was unprecedented and created uncertainty in terms of workforce requirements. This study highlights the personal impact and professional responses of novice practitioners, who felt a sense of duty and care to help support the NHS and others. IMPLICATIONS FOR PRACTICE: This will help in the understanding of the transition of student into employment and what wider support needs to be in place prior, during and after this phase.

Physical activity, sedentary behaviour and cannabis use in 15,822 US adults: cross-sectional analyses from NHANES.

OBJECTIVES: The aim was to analyse the overall and sex-specific associations between cannabis use and physical activity and sedentary behaviour. STUDY DESIGN: Cross-sectional analyses from the National Health and Nutrition Examination Survey (NHANES). METHODS: Data on cannabis use and leisure time physical activity and sedentary behaviour from NHANES cycles 2007-2008 to 2015-2016 were analysed. Multivariable regression models were carried out. RESULTS: About 15,822 participants were analysed (mean age ± standard error = 37.5 ± 0.19 years, range 20-59 years). Significantly higher odds were found for being active and ever used cannabis in the overall sample (odds ratio [OR] = 1.2, 95% confidence interval [CI]: 1.1-1.4) and in males (OR = 1.3, 95% CI: 1.1 to 1.5) and females (OR = 1.2, 95% CI: 1.0-1.4), respectively. In respective of sedentary behaviour, ever used cannabis was associated with higher odds of TV viewing ≥2 h/day in the overall sample (OR = 1.2, 95% CI: 1.0-1.4). However, this association was observed in males only (OR = 1.3, 95% CI: 1.1-1.6). Ever used cannabis was associated with total sitting time (beta-coefficient = 0.3, 95%CI: 0.1-0.4), which was more evident in females (beta-coefficient = 0.4, 95% CI: 0.1-0.6). CONCLUSIONS: Cannabis consumption was associated with higher levels of physical activity and sitting time. When intervening to reduce cannabis consumption in the US populations, it may be appropriate to promote physical activity and ensure physical activity is maintained once cannabis consumption is stopped.

The description and definition of Emergency Department Pharmacist Practitioners in the United Kingdom (the ENDPAPER study).

Background Due to a shortage of emergency department doctors and nurses, hospitals have started to employ pharmacists who have additional clinical skills, known as Emergency Department Pharmacist Practitioners, to help deliver services. Objective To describe, compare and define the Emergency Department Pharmacist Practitioner role. Setting UK emergency departments. Method Using a purpose developed questionnaire hosted on a tablet computer, Emergency Department Pharmacist Practitioners were asked to report their contribution to patient care and the wider emergency department over 10 work days. Main outcome measure Emergency Department Pharmacist Practitioners' work. Results Twenty Emergency Department Pharmacist Practitioners from 15 UK hospitals were recruited. Of 682 patients cared for, 4.8% (n=33) were of blue triage category (least urgent) and 4.1% (n=28) red (immediate need). Specific activities to inform patient diagnosis included clinical examinations (264/682 patients, 38.7%) and the review of investigation/test/procedure results (270, 39.6%). For treatment, EDPPs prescribed a total of 603 medicines (for administration in the ED) to 266 patients (39.0%) and performed procedures for 63 (9.2%). Eleven of the practitioners also took on the role of designated care provider (i.e. the healthcare professional with overall clinical responsibility) for at least some of their patients. From application of the care typology, all 20 practitioners carried out both 'traditional' and 'practitioner' activity and 9/20 of them sometimes provided more 'practitioner' than 'traditional' care to individual patients. Seven key role attributes were identified including how these pharmacists support patients with medical complaints and injuries of any severity and at any stage of their visit. Conclusion Emergency Department Pharmacist Practitioners combine traditional clinical pharmacy activities with more hands-on medical practise including being designated care provider. The role is versatile in that care and support provided to patients and the wider emergency department professional team is varied and therefore somewhat adaptable to situations which present.

What maximizes the effectiveness and implementation of technology-based interventions to support healthcare professional practice? A systematic literature review.

BACKGROUND: Technological support may be crucial in optimizing healthcare professional practice and improving patient outcomes. A focus on electronic health records has left other technological supports relatively neglected. Additionally, there has been no comparison between different types of technology-based interventions, and the importance of delivery setting on the implementation of technology-based interventions to change professional practice. Consequently, there is a need to synthesise and examine intervention characteristics using a methodology suited to identifying important features of effective interventions, and the barriers and facilitators to implementation. Three aims were addressed: to identify interventions with a technological component that are successful at changing professional practice, to determine if and how such interventions are theory-based, and to examine barriers and facilitators to successful implementation. METHODS: A literature review informed by realist review methods was conducted involving a systematic search of studies reporting either: (1) behavior change interventions that included technology to support professional practice change; or (2) barriers and facilitators to implementation of technological interventions. Extracted data was quantitative and qualitative, and included setting, target professionals, and use of Behaviour Change Techniques (BCTs). The primary outcome was a change in professional practice. A thematic analysis was conducted on studies reporting barriers and facilitators of implementation. RESULTS: Sixty-nine studies met the inclusion criteria; 48 (27 randomized controlled trials) reported behavior change interventions and 21 reported practicalities of implementation. The most successful technological intervention was decision support providing healthcare professionals with knowledge and/or person-specific information to assist with patient management. Successful technologies were more likely to operationalise BCTs, particularly "instruction on how to perform the behavior". Facilitators of implementation included aligning studies with organisational initiatives, ensuring senior peer endorsement, and integration into clinical workload. Barriers included organisational challenges, and design, content and technical issues of technology-based interventions. CONCLUSIONS: Technological interventions must focus on providing decision support for clinical practice using recognized behavior change techniques. Interventions must consider organizational context, clinical workload, and have clearly defined benefits for improving practice and patient outcomes.

Comparing accelerometer, pedometer and a questionnaire for measuring physical activity in bronchiectasis: a validity and feasibility study?

BACKGROUND: There are challenges for researchers and clinicians to select the most appropriate physical activity tool, and a balance between precision and feasibility is needed. Currently it is unclear which physical activity tool should be used to assess physical activity in Bronchiectasis. The aim of this research is to compare assessment methods (pedometer and IPAQ) to our criterion method (ActiGraph) for the measurement of physical activity dimensions in Bronchiectasis (BE), and to assess their feasibility and acceptability. METHODS: Patients in this analysis were enrolled in a cross-sectional study. The ActiGraph and pedometer were worn for seven consecutive days and the IPAQ was completed for the same period. Statistical analyses were performed using SPSS 20 (IBM). Descriptive statistics were used; the percentage agreement between ActiGraph and the other measures were calculated using limits of agreement. Feedback about the feasibility of the activity monitors and the IPAQ was obtained. RESULTS: There were 55 (22 male) data sets available. For step count there was no significant difference between the ActiGraph and Pedometer, however, total physical activity time (mins) as recorded by the ActiGraph was significantly higher than the pedometer (mean ± SD, 232 (75) vs. 63 (32)). Levels of agreement between the two devices was very good for step count (97% agreement); and variation in the levels of agreement were within accepted limits of ±2 standard deviations from the mean value. IPAQ reported more bouted- moderate - vigorous physical activity (MVPA) [mean, SD; 167(170) vs 6(9) mins/day], and significantly less sedentary time than ActiGraph [mean, SD; 362(115) vs 634(76) vmins/day]. There were low levels of agreement between the two tools (57% sedentary behaviour; 0% MVPA10+), with IPAQ under-reporting sedentary behaviour and over-reporting MVPA10+ compared to ActiGraph. The monitors were found to be feasible and acceptable by participants and researchers; while the IPAQ was accepta ble to use, most patients required assistance to complete it. CONCLUSIONS: Accurate measurement of physical activity is feasible in BE and will be valuable for future trials of therapeutic interventions. ActiGraph or pedometer could be used to measure simple daily step counts, but ActiGraph was superior as it measured intensity of physical activity and was a more precise measure of time spent walking. The IPAQ does not appear to represent an accurate measure of physical activity in this population. TRIAL REGISTRATION: Clinical Trials Registration Number NCT01569009 : Physical Activity in Bronchiectasis.

Statin prescription initiation and lifestyle behaviour: a primary care cohort study.

BACKGROUND: Statin prescribing and healthy lifestyles contribute to declining cardiovascular disease mortality. Recent guidelines emphasise the importance of giving lifestyle advice in association with prescribing statins but adherence to healthy lifestyle recommendations is sub-optimal. However, little is known about any change in patients' lifestyle behaviours when starting statins or of their recall of receiving advice. This study aimed to examine patients' diet and physical activity (PA) behaviours and their recall of lifestyle advice following initiation of statin prescribing in primary care. METHOD: In 12 general practices, patients with a recent initial prescription of statin therapy, were invited to participate. Those who agreed received a food diary by post, to record food consumed over 4 consecutive days and return to the researcher. We also telephoned participants to administer brief validated questionnaires to assess typical daily diet (DINE) and PA level (Godin). Using the same methods, food diaries and questionnaires were repeated 3 months later. At both times participants were asked if they had changed their behaviour or received advice about their diet or PA. RESULTS: Of 384 invited, 122 (32 %) participated; 109 (89.3 %) completed paired datasets; 50 (45.9 %) were male; their mean age was 64 years. 53.2 % (58/109) recalled receiving lifestyle advice. Of those who did, 69.0 % (40/58) reported having changed their diet or PA, compared to 31.4 % (16/51) of those who did not recall receiving advice. Initial mean daily saturated fat intake (12.9 % (SD3.5) of total energy) was higher than recommended; mean fibre intake (13.8 g/day (SD5.5)), fruit/vegetable consumption (2.7 portions/day (SD1.3)) and PA levels (Godin score 7.1 (SD13.9)) were low. Overall, although some individuals showed evidence of behaviour change, there were no significant changes in the proportions who reported high or medium fat intake (42.2 % v 49.5 %), low fibre (51.4 % v 55.0 %), or insufficient PA (80.7 % v 83.5 %) at 3-month follow-up. CONCLUSION: Whilst approximately half of our cohort recalled receiving lifestyle advice associated with statin prescribing this did not translate into significant changes in diet or PA. Further research is needed to explore gaps between people's knowledge and behaviours and determine how best to provide advice that supports behaviour change.

A systematic review of the prevalence and incidence of prescribing errors with high-risk medicines in hospitals.

WHAT IS KNOWN: Prescribing errors are the most common type of error in the medication use process. However, there is a paucity of literature regarding the prevalence or incidence of prescribing errors in high-risk medicines (HRMs). HRMs bear a heightened risk of causing significant patient harm when they are used in error. OBJECTIVE: The aim of this research was to systematically investigate the literature regarding the prevalence and incidence of prescribing errors in HRMs in inpatient settings. METHODS: A search strategy was developed based on four categories of keywords: prescribing errors, HRMs, hospital inpatients, and prevalence or incidence. All keywords were searched for in Medline, Embase, Cochrane and the International Pharmaceutical Abstracts. The search was limited to English quantitative studies that reported the incidence or prevalence of prescribing errors by medical prescribers, whether they were seniors or juniors, since 1985. RESULTS: Of the 3507 records identified, nine studies met the review criteria. The most frequent denominator in the included studies was medication orders, in eight studies, ranged from 0·24 to 89·6 errors per 100 orders of HRMs. Two studies reported 107 and 218 errors per 100 admissions prescribed HRMs, and one study reported 27·2 errors per 100 prescriptions with a HRM. The incidence of prescribing errors could not be calculated. WHAT IS NEW AND CONCLUSION: The prevalence of prescribing errors in HRMs in the inpatient setting has a very wide range that reflects the different data collection methods used within the included studies. Future studies in prescribing errors should use standardized approaches to enable comparison.

Bundle interventions used to reduce prescribing and administration errors in hospitalized children: a systematic review.

WHAT IS KNOWN AND OBJECTIVE: Bundle interventions are becoming increasingly used as patient safety interventions. The objective of this study was to describe and categorize which bundle interventions are used to reduce prescribing errors (PEs) and administration errors (AEs) in hospitalized children and to assess the quality of the published literature. METHODS: Articles published in English and Arabic between 1985 and September 2015 were sought in MEDLINE, EMBASE and CINHAL. Bibliographies of included articles were screened for additional studies. We included any study with a comparator group reporting rates of PEs and AEs. Two authors independently extracted data, classified interventions in each bundle and assessed the studies for potential risk of bias. Constituent interventions of the bundles were categorized using both the Cochrane Effective Practice and Organization of Care Group (EPOC) taxonomy of intervention and the Behavioural Change Wheel (BCW). RESULTS AND DISCUSSION: Seventeen studies met the inclusion criteria. All bundles contained interventions that were either professional, organizational or a mixture of both. According to the BCW, studies used interventions with functions delivering environmental restructuring (17/17), education (16/17), persuasion (4/17), training (3/17), restriction (3/17), incentivization (1/17), coercion (1/17), modelling (1/17) and enablement (1/17). Nine studies had bundles with two intervention functions, and eight studies had three or more intervention functions. All studies were low quality before/after studies. Selection bias varied between studies. Performance bias was either low or unclear. Attrition bias was unclear, and detection bias was rated high in most studies. Ten studies described the interventions fairly well, and seven studies did not adequately explain the interventions used. WHAT IS NEW AND CONCLUSION: This novel analysis in a systematic review showed that bundle interventions delivering two or more intervention functions have been investigated but that the study quality was too poor to assess impact.

Factors influencing nurse and pharmacist willingness to take or not take responsibility for non-medical prescribing.

BACKGROUND: In the UK, the majority of non-medical prescribers (NMPs) are nurses or pharmacists working in community or primary care. However, little is known about what influences their decisions to prescribe, unlike with medical prescribing. It is also unclear whether the medical findings can be extrapolated, given their very different prescribing training. OBJECTIVES: To explore the factors influencing whether nurse and pharmacist NMPs in community and primary care settings take responsibility for prescribing. METHODS: Initially, 20 NMPs (15 nurses and 5 pharmacists) were purposively selected and interviewed using the critical incident technique about situations where they felt it was inappropriate for them to take responsibility for prescribing or where they were uneasy about doing so. In addition, more general factors influencing their decision to take or not take prescribing responsibility were discussed. Subsequently, the themes from the interview analysis were validated in three focus groups with a total of 10 nurse NMPs. All data were analyzed using a constant comparison approach. RESULTS: Fifty-two critical incidents were recorded--12 from pharmacist NMPs and 40 from nurse NMPs. Participants experienced situations where they were reluctant to accept responsibility for prescribing. Perceptions of competency, role and risk influenced their decision to prescribe. Workarounds such as delaying the prescribing decision or refer the patient to a doctor were used. CONCLUSIONS: For NMPs to feel more confident about taking responsibility for prescribing, these issues of competency, role and perceived risk need to be addressed. Roles of NMPs must be clear to colleagues, doctors and patients. Training and support must be provided to enable professional development and increasing competence of NMPs.

Molecular mechanisms of acrolein-mediated myelin destruction in CNS trauma and disease.

Myelin is a critical component of the nervous system facilitating efficient propagation of electrical signals and thus communication between the central and peripheral nervous systems and the organ systems that they innervate throughout the body. In instances of neurotrauma and neurodegenerative disease, injury to myelin is a prominent pathological feature responsible for conduction deficits, and leaves axons vulnerable to damage from noxious compounds. Although the pathological mechanisms underlying myelin loss have yet to be fully characterized, oxidative stress (OS) appears to play a prominent role. Specifically, acrolein, a neurotoxic aldehyde that is both a product and an instigator of OS, has been observed in studies to elicit demyelination through calcium-independent and -dependent mechanisms and also by affecting glutamate uptake and promoting excitotoxicity. Furthermore, pharmacological scavenging of acrolein has demonstrated a neuroprotective effect in animal disease models, by conserving myelin's structural integrity and alleviating functional deficits. This evidence indicates that acrolein may be a key culprit of myelin damage while acrolein scavenging could potentially be a promising therapeutic approach for patients suffering from nervous system trauma and disease.

An investigation into the content validity of the Antimicrobial Self-Assessment Toolkit for NHS Trusts (ASAT v15a) using cognitive interviews with antimicrobial pharmacists.

WHAT IS KNOWN AND OBJECTIVE: The Antimicrobial Self-Assessment Toolkit for NHS Trusts (ASAT) was developed to evaluate the organizational strategies used to implement hospital-based antimicrobial stewardship programmes. An iterative approach was used to develop ASAT v15a, which has been previously investigated for face validity; however, further investigation into other types of validity was required. Therefore, the aim of this study was to investigate the content validity of ASAT v15a and hence modify and improve the content validity of the toolkit. METHODS: A purposive sample of eight antimicrobial pharmacists was interviewed using cognitive interviewing techniques from within the former North-west Strategic Health Authority in England. Respondents were asked to 'think aloud' and to verbally express their thought processes as they generated responses to each question with the ASAT. RESULTS: There were no cognitive difficulties reported by respondents in response to 26/83 (31·3%) questions within the ASAT. However, cognitive difficulties were reported by respondents at each stage of the cognitive processing pathway in response to 57/83 (68·7%) questions. These difficulties were comprehension/interpretation in 27/83 (32·5%) questions, information retrieval in 10/83 (12%) questions, judgment/decision in 6/83 (7·2%) questions and response generation/formatting in 13/83 (15·7%) questions. Other findings included disagreement with the weightings applied to 13/83 (15·7%) questions. Respondents recommended that these questions should be modified to reflect their impact on hospital-based antimicrobial stewardship programmes (ASPs). Based on these findings, modifications were made to ASAT v15a to produce the next iteration (ASAT v16). Furthermore, respondents indicated that the role of clinical microbiologists was underrepresented in the current version of the toolkit; therefore, seven proposed questions were drafted, based on a literature review. WHAT IS NEW AND CONCLUSION: Cognitive interviews were effectively able to detect problems encountered by respondents along the cognitive processing pathway by identifying words and/or phrases that required further modifications. Also, this method highlighted that there was a disparity between the respondents' interpretation and the ASAT developers' intent within some questions. Although respondents indicated that the toolkit evaluated the most pertinent components of ASPs, further modifications and testing would be required to improve its validity. These results highlight the importance of the inclusion of end-users in the development of reporting and/or evaluation tools or questionnaires.

Exploring lay views on physical activity and their implications for public health policy. A case study from East Belfast.

It is now recognised that inactive lifestyles underpin much of the disease burden evident in the richer nations of the world. Indeed, the WHO has identified physical inactivity as a 'global public health problem' and has established minimum physical activity (PA) targets for people at different stages of the life-course. Yet, according to WHO, just under 1/3 of working age adults across the globe meet those targets and it is not at all clear how the disjunction between the recommendations of policy makers and the behaviour of ordinary people might be surmounted. Using an opportunity to examine the impact of an urban regeneration project on community residents in East Belfast (Northern Ireland) this paper examines the views of some 113 people on how to increase rates of PA in an area of multiple deprivation. The results of the analysis suggest that lay people rarely consider PA as a discrete issue, or one that centres on individuals and their motivation, but rather as one component in a complex web of concerns, processes and events that include such things as the actions of neighbours and relatives, material and political environments, vandalism, violence, and the weather. We explore and unravel the nature of those concerns using novel methods of content analysis that generate 'issue webs'. Particular attention is paid to the ways in which lay people conceptualize 'activity' and to the manner in which they point to ways of encouraging activity that are rooted in everyday life rather than in the corpocentric, agent-centred and often sport dominated strategies favoured by local policy makers. Our results support those who argue that interventions to increase rates of PA need to move beyond behavioural approaches that focus on individuals and consider the social, political and material contexts in which 'activity' occurs.

Scleraxis expression is coordinately regulated in a murine model of patellar tendon injury.

This study investigated the expression of Scleraxis in a murine model of patellar tendon injury in which the central third of the patellar tendon was unilaterally injured. The presence of tendon pathology was assessed using dual photon microscopy, conventional histology and microCT. Tendon pathology was also quantified noninvasively over a 12-week period using high-frequency ultrasound and laser Doppler flowmetry. Gene expression (Scx, Tnmd, and Col1a1) was determined at defined end-points (1, 4, 8, and 12 weeks) using qPCR on RNA from individual patellar tendons on injured and uninjured sides. There was significant development of tendon pathology as gauged by ultrasound and laser Doppler over 12 weeks. Injured tendons demonstrated significant histological and microCT evidence of pathological change, and disorganized collagen with reduced density. The expression of Scx and Col1a1 was unchanged at 1 week, significantly upregulated at 4 and 8 weeks, and had returned to baseline by 12 weeks. Tnmd expression was unchanged at 1 week, and significantly increased at 4, 8, and 12 weeks. Patellar tendon injury was associated with marked increases in the expression of Scx, Tnmd, and Col1a1. Our data suggest new roles for Scleraxis in coordinating the response to injury in the pathogenesis of tendon disorders.

Anti-acrolein treatment improves behavioral outcome and alleviates myelin damage in experimental autoimmune encephalomyelitis mouse.

Oxidative stress is considered a major contributor in the pathology of multiple sclerosis (MS). Acrolein, a highly reactive aldehyde byproduct of lipid peroxidation, is thought to perpetuate oxidative stress. In this study, we aimed to determine the role of acrolein in an animal model of MS, experimental autoimmune encephalomyelitis (EAE) mice. We have demonstrated a significant elevation of acrolein protein adduct levels in EAE mouse spinal cord. Hydralazine, a known acrolein scavenger, significantly improved behavioral outcomes and lessened myelin damage in spinal cord. We postulate that acrolein is an important pathological factor and likely a novel therapeutic target in MS.

The retinoic acid binding protein CRABP2 is increased in murine models of degenerative joint disease.

INTRODUCTION: Osteoarthritis (OA) is a debilitating disease with poorly defined aetiology. Multiple signals are involved in directing the formation of cartilage during development and the vitamin A derivatives, the retinoids, figure prominently in embryonic cartilage formation. In the present study, we examined the expression of a retinoid-regulated gene in murine models of OA. METHODS: Mild and moderate forms of an OA-like degenerative disease were created in the mouse stifle joint by meniscotibial transection (MTX) and partial meniscectomy (PMX), respectively. Joint histopathology was scored using an Osteoarthritis Research Society International (OARSI) system and gene expression (Col1a1, Col10a1, Sox9 and Crabp2) in individual joints was determined using TaqMan quantitative PCR on RNA from microdissected articular knee cartilage. RESULTS: For MTX, there was a significant increase in the joint score at 10 weeks (n = 4, p < 0.001) in comparison to sham surgeries. PMX surgery was slightly more severe and produced significant changes in joint score at six (n = 4, p < 0.01), eight (n = 4, p < 0.001) and 10 (n = 4, p < 0.001) weeks. The expression of Col1a1 was increased in both surgical models at two, four and six weeks post-surgery. In contrast, Col10a1 and Sox9 for the most part showed no significant difference in expression from two to six weeks post-surgery. Crabp2 expression is induced upon activation of the retinoid signalling pathway. At two weeks after surgery in the MTX and PMX animals, Crabp2 expression was increased about 18-fold and about 10-fold over the sham control, respectively. By 10 weeks, Crabp2 expression was increased about three-fold (n = 7, not significant) in the MTX animals and about five-fold (n = 7, p < 0.05) in the PMX animals in comparison to the contralateral control joint. CONCLUSIONS: Together, these findings suggest that the retinoid signalling pathway is activated early in the osteoarthritic process and is sustained during the course of the disease.