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Abstract Background Patient-oriented research is now widely regarded as key to improving health systems and patient outcomes. This shift toward meaningful patient involvement in health research has sparked a growing interest in patient-oriented research training across Canada. Yet some barriers to participation, including distance and scheduling constraints, may impede the provision of in-person patient-oriented research training. Virtual course delivery options may help surmount those barriers, as well as offer unique pedagogical advantages. Objective To help increase patient-oriented research training uptake, the research team adapted the Canadian Institutes of Health Research’s (CIHR) Strategy for Patient-Oriented Research’s Foundations for Patient-Oriented Research course to a virtual format. The course consists of three modules, which focus respectively on patient-oriented research, health research methods, and teamwork skills. The current evaluation of this virtual delivery examines how a diverse set of participants received the online course. Methods Course participants from a variety of professional backgrounds, including researchers, patients, clinicians, and policy decision-makers, were recruited from across Canada to participate in the adapted course. Participant and facilitator feedback was solicited via online surveys that were distributed shortly after the delivery of each module. Results Over the span of the current project, the online course was delivered seven times across Canada. A total of 189 learners and 12 facilitators participated in the course. We received 89 completed feedback surveys in total. These included a total of 78 responses from learners, with 22 on Module 1, 32 on Module 2, and 24 on Module 3, in addition to 11 responses from facilitators. Overall, participants and facilitators were very satisfied with the course, indicating a successful adaptation from traditional to online delivery. Survey respondents were especially pleased with the course’s co-learning elements, which exposed them to fresh perspectives and real patient voices, as well as ample opportunity for discussion. Some participants offered recommendations for minor course revisions. Future iterations of the course will reflect participant and facilitator feedback to enhance accessibility via minor changes to course format (e.g., shorter live sessions), content (e.g., more concrete examples), and workload (e.g., reduced pre-work requirements). Conclusions Sustainable and effective health care depends on health research that includes active partnerships across diverse populations. These collaborative relationships are fostered by strong capacity in patient-oriented research, which in turn hinges on widely accessible training opportunities. This online course overcomes common barriers to face-to-face training and offers the accessible, inclusive training environment required for sustained progress in patient-oriented research.

International and transnational cooperation is needed to strengthen environmental governance initiatives with advanced technologies. In January 2023, Ontario Tech University hosted a symposium entitled Tech With a Green Governance Conscience: Exploring the Technology–Environmental Policy Nexus. Attendees spanned diverse disciplines, sectors, and countries, bringing unique and diverse perspectives to the technology–environmental policy nexus. Emergent themes arising from the symposium include the role of artificial intelligence in environmental governance, while eliminating the detrimental social impacts associated with these advanced technologies via algorithmic bias, misunderstanding, and unaccountability. The symposium explored the tech–society–ecology interface, such as the authoritarian intensification of digitalized environmental governance, “technocracy”, and the ethical implications of sacrificing democratic legitimacy in the face of imminent environmental destruction. Select participants (i.e., co-authors) at the symposium provided input on a preliminary framework, which led to this perspective article focused on the politics surrounding green governance in the 21st century. We conclude that while emerging technologies are being deployed to address grand environmental challenges such as climate change, biodiversity loss, and resource depletion, the use of these various technologies for progressive environmental policy development and enforcement requires co-productivist approaches to constructive technology assessments and embracing the concept of technologies of humility. This necessitates a space for dialogue, reflection, and deliberation on leading adaptive environmental governance in the face of power and politics, as we interrogate the putative neutrality of advanced technology and techno-solutionism.

Abstract Background Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed to manage anxiety in adults with an autism diagnosis. However, their effectiveness and adverse effect profile in the autistic population are not well known. This trial aims to determine the effectiveness and cost-effectiveness of the SSRI sertraline in reducing symptoms of anxiety and improving quality of life in adults with a diagnosis of autism compared with placebo and to quantify any adverse effects. Methods STRATA is a two-parallel group, multi-centre, pragmatic, double-blind, randomised placebo-controlled trial with allocation at the level of the individual. It will be delivered through recruiting sites with autism services in 4 regional centres in the United Kingdom (UK) and 1 in Australia. Adults with an autism diagnosis and a Generalised Anxiety Disorder Assessment (GAD-7) score ≥ 10 at screening will be randomised 1:1 to either 25 mg sertraline or placebo, with subsequent flexible dose titration up to 200 mg. The primary outcome is GAD-7 scores at 16 weeks post-randomisation. Secondary outcomes include adverse effects, proportionate change in GAD-7 scores including 50% reduction, social anxiety, obsessive-compulsive symptoms, panic attacks, repetitive behaviours, meltdowns, depressive symptoms, composite depression and anxiety, functioning and disability and quality of life. Carer burden will be assessed in a linked carer sub-study. Outcome data will be collected using online/paper methods via video call, face-to-face or telephone according to participant preference at 16, 24 and 52 weeks post-randomisation, with brief safety checks and data collection at 1–2, 4, 8, 12 and 36 weeks. An economic evaluation to study the cost-effectiveness of sertraline vs placebo and a QuinteT Recruitment Intervention (QRI) to optimise recruitment and informed consent are embedded within the trial. Qualitative interviews at various times during the study will explore experiences of participating and taking the trial medication. Discussion Results from this study should help autistic adults and their clinicians make evidence-based decisions on the use of sertraline for managing anxiety in this population. Trial registration ISRCTN, ISRCTN15984604 . Registered on 08 February 2021. EudraCT 2019-004312-66. ANZCTR ACTRN12621000801819. Registered on 07 April 2021.

BackgroundPeople with chronic diseases tend to experience more mental health issues than their peers without these health conditions. Mental health chatbots offer a potential source of mental health support for people with chronic diseases. ObjectiveThe aim of this study was to determine whether a mental health chatbot can improve mental health in people with chronic diseases. We focused on 2 chronic diseases in particular: arthritis and diabetes. MethodsIndividuals with arthritis or diabetes were recruited using various web-based methods. Participants were randomly assigned to 1 of 2 groups. Those in the treatment group used a mental health chatbot app (Wysa [Wysa Inc]) over a period of 4 weeks. Those in the control group received no intervention. Participants completed measures of depression (Patient Health Questionnaire–9), anxiety (Generalized Anxiety Disorder Scale–7), and stress (Perceived Stress Scale–10) at baseline, with follow-up testing 2 and 4 weeks later. Participants in the treatment group completed feedback questions on their experiences with the app at the final assessment point. ResultsA total of 68 participants (n=47, 69% women; mean age 42.87, SD 11.27 years) were included in the analysis. Participants were divided evenly between the treatment and control groups. Those in the treatment group reported decreases in depression (P

Abstract Objective To determine the carbon savings potential of incorporating virtual care into surgical care pathways for pediatric patients with obstructive sleep apnea or otitis media with effusion. Methods Pediatric patients with obstructive sleep apnea or otitis media with effusion were not enrolled, instead, a modeling cohort study design was used. This study utilized the British Columbia healthcare system and geography to model emissions. Care pathways were developed for pediatric patients with obstructive sleep apnea or otitis media with effusion requiring care at a tertiary pediatric center. Home addresses were located at the geographical center of the two most populated municipalities within each of the 10 most populated regional districts in 2020. Virtual visits replaced up to three clinically equivalent in‐person visits. Emissions (kgCO2e) for transport and virtual visits were estimated. Population‐weighted means and descriptive statistics were calculated. Results Utilizing 1, 2, or 3 virtual visits in the obstructive sleep apnea care pathway yielded potential emissions savings of 19.9%, 39.9%, and 59.8% respectively. Integrating 1, 2, or 3 virtual visits into the otitis media with effusion care pathway produced potential emissions savings of 16.6%, 33.2%, and 49.7%, respectively. Integrating 3 virtual visits can save up to 2156.8 kgCO2e per patient. Conclusions Appropriately conducting up to 50% of clinical encounters virtually for children with obstructive sleep apnea or otitis media with effusion reduced theoretical carbon emissions. For a single child, emission savings could reach over 2150 kgCO2e. Level of Evidence Level 5.

Flexible social attention, including visually attending to social interaction partners, coupled with positive affect may facilitate adaptive social functioning. However, most research assessing social attention relies on static computer-based paradigms, overlooking the dynamics of social interactions and limiting understanding of individual differences in the deployment of naturalistic attention. The current study used mobile eye-tracking to examine relations between social attention, expressed affect, and behavioral inhibition during naturalistic play in young children. Children (N = 28, M[subscript age] = 6.12, 46.4% girls, 92.9% White) participated in a 5-min free play with a novel age- and sex-matched peer while mobile eye-tracking data were collected. Interactions were coded for social attention and expressed affect and modeled second-by-second, generating 4,399 observations. Children spent more time dwelling on toys than on peers or anywhere else in the room. Further analyses demonstrated children were almost twice as likely to gaze at their peer when simultaneously self-expressing positive affect. Additionally, children were more than twice as likely and more than three times as likely to self-express positive affect when dwelling on peer or in the presence of peer-expressed positive affect, respectively. Behavioral inhibition was not significantly related to social attention. However, children higher in behavioral inhibition were less likely to self-express positive affect in the presence of peer-expressed positive affect. The current results provide a snapshot of relations between social attention, expressed affect and individual differences during play and provide guidance for future work assessing the roles of social attention and positive affect in facilitating positive social interactions.

Background: The chloroplast genomes of Cactaceae exhibit boundary modifications in the inverted repeat regions (IRs), gene inversions, and deletions. Among nine Mammillaria species, three distinct chloroplast structures have been identified, although not all of these correspond to the morphology-based classification of the genus. Question: Is there a distinct chloroplast genome structure in the species of Mammillaria series Stylothelae? Studied species: Mammillaria bocasana and M. erythrosperma. Study site and dates: Mexico from 2019 to 2023. Methods: Chloroplast DNA was sequenced, and chloroplast genomes were de novo assembled using the Fast-Plast program. Complete plastome sequences were annotated and verified. The sequences were aligned in MAUVE program to detect possible structural changes. A maximum likelihood phylogeny was executed to evaluate the relationships of the studied species. Results: The plastomes ranged from 107,368 bp in Mammillaria bocasana to 108,069 bp in M. erythrosperma. Both presented a quadripartite structure and contained 108 genes. The IRs were ~ 1,600 bp long and included the genes rpl2, rpl23 (pseudo), and trnI-CAU. MAUVE identified a ~ 21 kb inversion in the large single copy containing a block of genes related to photosynthesis. The phylogenetic analysis placed both species in a single clade separated from the other species within Mammillaria subg. Mammillaria. Conclusions: The studied species of Mammillaria series Stylothelae exhibited a different and synapomorphic chloroplast genome structure. Other Mammillaria chloroplast genome structures have evolved independently in different lineages.

Background Conservative therapies are recommended as initial treatment for male lower urinary tract symptoms. However, there is a lack of evidence on effectiveness and uncertainty regarding approaches to delivery. Objective The objective was to determine whether or not a standardised and manualised care intervention delivered in primary care achieves superior symptomatic outcome for lower urinary tract symptoms to usual care. Design This was a two-arm cluster randomised controlled trial. Setting The trial was set in 30 NHS general practice sites in England. Participants Participants were adult men (aged ≥ 18 years) with bothersome lower urinary tract symptoms. Interventions Sites were randomised 1 : 1 to deliver the TReatIng Urinary symptoms in Men in Primary Health care using non-pharmacological and non-surgical interventions trial intervention or usual care to all participants. The TReatIng Urinary symptoms in Men in Primary Health care using non-pharmacological and non-surgical interventions intervention comprised a standardised advice booklet developed for the trial from the British Association of Urological Surgeons’ patient information sheets, with patient and expert input. Patients were directed to relevant sections by general practice or research nurses/healthcare assistants following urinary symptom assessment, providing the manualised element. The healthcare professional provided follow-up contacts over 12 weeks to support adherence to the intervention. Main outcome measures The primary outcome was the validated patient-reported International Prostate Symptom Score 12 months post consent. Rather than the minimal clinically important difference of 3.0 points for overall International Prostate Symptom Score, the sample size aimed to detect a difference of 2.0 points, owing to the recognised clinical impact of individual symptoms. Results A total of 1077 men consented to the study: 524 in sites randomised to the intervention arm (n = 17) and 553 in sites randomised to the control arm (n = 13). A difference in mean International Prostate Symptom Score at 12 months was found (adjusted mean difference of –1.81 points, 95% confidence interval –2.66 to –0.95 points), with a lower score in the intervention arm, indicating less severe symptoms. Secondary outcomes of patient-reported urinary symptoms, quality of life specific to lower urinary tract symptoms and perception of lower urinary tract symptoms all showed evidence of a difference between the arms favouring the intervention. No difference was seen between the arms in the proportion of urology referrals or adverse events. In qualitative interviews, participants welcomed the intervention, describing positive effects on their symptoms, as well as on their understanding of conservative care and their attitude towards the experience of lower urinary tract symptoms. The interviews highlighted that structured, in-depth self-management is insufficiently embedded within general practitioner consultations. From an NHS perspective, mean costs and quality-adjusted life-years were similar between trial arms. The intervention arm had slightly lower mean costs (adjusted mean difference of –£29.99, 95% confidence interval –£109.84 to £22.63) than the usual-care arm, and a small gain in quality-adjusted life-years (adjusted mean difference of 0.001, 95% confidence interval –0.011 to 0.014). Conclusions The intervention showed a small, sustained benefit for men’s lower urinary tract symptoms and quality of life across a range of outcome measures in a UK primary care setting. Qualitative data showed that men highly valued the intervention. Intervention costs were marginally lower than usual-care costs. Limitations of the study included that trial participants were unmasked, with limited diversity in ethnicity and deprivation level. Additional research is needed to assess the applicability of the intervention for a more ethnically diverse population.. Trial registration This trial is registered as ISRCTN11669964. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/90/03) and is published in full in Health Technology Assessment; Vol. 28, No. 13. See the NIHR Funding and Awards website for further award information. Plain language summary Urinary problems among men become more common with age. Nearly one-third of all men aged > 65 years experience some urinary symptoms, which can have a substantial effect on their daily lives. Symptoms include needing to pass urine more often, urgently or during the night, and difficulties in passing urine. Men are usually diagnosed and treated by their general practitioner, and should be offered advice on controlling their symptoms themselves (e.g. lifestyle changes and exercises) before trying tablets or surgery. However, it is not known how helpful such advice is, and how general practices can effectively provide it. Thirty general practices in the West of England and Wessex took part in the study. Practices were split into two groups, with each practice providing either the TReatIng Urinary symptoms in Men in Primary Health care using non-pharmacological and non-surgical interventions care package or the practice’s usual care to all of its patients in the trial. The TReatIng Urinary symptoms in Men in Primary Healthcare using nonpharmacological and non-surgical interventions care package included a booklet of advice to help control urinary symptoms, with a nurse or healthcare assistant directing men to relevant sections according to their symptoms, and providing follow-up contacts. We mainly assessed the benefits of the TReatIng Urinary symptoms in Men in Primary Healthcare using nonpharmacological and non-surgical interventions care package, compared with usual care, by using a questionnaire on urinary symptoms completed by participants. A total of 1077 men with urinary symptoms that bothered them joined the study. The main result was that men reported greater improvement in urinary symptoms with the TRIUMPH care package than with usual care, 12 months after joining the study. We also found that men receiving the TRIUMPH care package had a slight improvement in quality of life and outlook on their urinary symptoms. There was no difference between the two groups in the number of patients referred to hospital for treatment, the type, number and severity of side effects or cost to the NHS. Overall, the TRIUMPH care package was more effective in treating men with urinary symptoms than usual care by their general practice. Scientific summary Background Lower urinary tract symptoms (LUTS) can relate to urinary storage or voiding. Among men, the prevalence and severity of symptoms increase with age, with a substantial impact on quality of life. The majority of men presenting with urinary symptoms are assessed and managed by their general practitioner (GP) in the first instance, with conservative therapies recommended as initial treatment. However, there is a lack of evidence on the effectiveness of conservative therapies, and uncertainty regarding approaches to delivery. Provision in primary care is variable and can be time and resource limited, and GPs require practical resources to enhance patient engagement with such interventions. The TReatIng Urinary symptoms in Men in Primary Health care using non-pharmacological and non-surgical interventions (TRIUMPH) trial aimed to address this need in primary care. Objectives The key aim of this research was to determine whether or not a standardised and manualised care intervention achieves superior symptomatic outcome, compared with usual care, for male LUTS, with a primary outcome of overall International Prostate Symptom Score (IPSS) measured 12 months after consent, in a primary care setting. Secondary objectives were to compare the two trial arms with regard to: disease-specific quality of life symptomatic outcomes cost effectiveness relative harms use of NHS resources overall quality of life and general health acceptability of assessment and provision of care patients’ perception of their LUTS. Design This was a pragmatic two-arm cluster randomised controlled trial randomising general practice sites 1 : 1 between a care pathway based on a standardised and manualised care intervention (intervention arm) and one based on usual care (comparator arm) for men with LUTS. The trial design included an internal pilot recruitment phase of 4 months’ duration, primarily to verify feasibility of recruitment before progression to the main phase of the trial. Setting Thirty general practice sites were recruited within nine Clinical Commissioning Groups across the West of England and Wessex Clinical Research Network (CRN) regions in the UK. Participants were identified and recruited from these sites. Participants General Practice Recruitment The CRNs invited general practices to express an interest in taking part in the study. To achieve a balanced range of practices, the following factors were considered in practice selection: number of potentially eligible patients, on conduct of a preliminary database search patient list size deprivation score (calculated using a general practice’s postcode) preference for method of intervention delivery (by practice staff or trial research nurses) treatment room space available for intervention delivery. Participating sites underwent site initiation training. An internal pilot phase was conducted with eight initial sites over a period of 4 months before the main phase of the trial. Participant recruitment This was a pragmatic trial in adult men who considered themselves to have bothersome LUTS and who had presented to primary care within the preceding 5 years with at least one symptom of LUTS. Only men already known to have LUTS (prevalent cases) were screened for inclusion in the trial. Screening was undertaken once by each site pre randomisation, so men newly presenting with LUTS (incident cases) after site randomisation were not included. Interventions Practices were randomised 1 : 1 to deliver the TRIUMPH intervention or a usual-care pathway. The TRIUMPH intervention comprises a LUTS advice booklet developed for the trial from the British Association of Urological Surgeons’ patient information sheets, with patient and expert input, providing the standardised element. Practices in the intervention arm could choose whether the intervention was delivered by central study research nurses or general practice nurses/healthcare assistants (HCAs), who received a 1-hour training session. Patients were directed to relevant sections by the nurses/HCA following symptom assessment, providing the manualised element. The healthcare professional (HCP) provided follow-up contacts over 12 weeks to encourage adherence. Usual care (the comparator arm for the TRIUMPH trial) in this study requested that sites continue to follow their standard local practice for trial patients in terms of delivery and follow-up. Main outcome measures The primary outcome measure was the patient-reported IPSS at 12 months after consent. Key secondary outcomes included quality of life, patient-reported urinary symptoms, adverse events, referrals to secondary care, patient perception of their LUTS, cost effectiveness, number of GP consultations and a qualitative evaluation of patients’ experiences of the intervention. Patient-reported outcomes were collected by questionnaire at baseline and at 6 and 12 months. Other clinical outcomes and NHS resource use were extracted from primary care electronic medical records a minimum of 1 month after the final participant at each site had completed the 12-month follow-up. Qualitative interviews were conducted throughout the trial. Results The trial was successful in meeting general practice site recruitment targets, and participant recruitment exceeded that anticipated. In total, 1077 men consented to the study: 524 in sites randomised to the intervention arm (n = 17) and 553 in sites randomised to the control arm (n = 13). A total of 887 patients (82%) were included in the primary analysis at 12 months post consent. The treatment groups were broadly balanced on baseline characteristics, but the primary outcome measure (IPSS) was slightly lower in the intervention arm than in the usual-care arm (intervention: 13.62 points; usual care: 14.59 points). The intervention was successfully delivered: 98% of men received their intervention booklet and 90% had all three contacts forming the intervention. The primary outcome analysis found that, although there was a reduction in IPSS between baseline and 12 months in both arms, suggesting improved symptoms, symptom improvement was greater in the intervention arm [–1.81, 95% confidence interval (CI) –2.66 to –0.95]. The difference was smaller than the difference we sought to detect in the sample size calculation of 2 points in overall IPSS, and the minimal clinically important difference of 3 points. The improvement in IPSS, however, was mirrored by improvements in the secondary outcomes of incontinence (measured using the International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form), IPSS quality-of-life measures and patients’ perception of their LUTS (measured using the Brief Illness Perception Questionnaire). The primary analysis estimates were robust to ways of accounting for clustering and multiple imputation of missing data. High levels of adherence to intervention delivery meant that per-protocol analyses largely reflected the primary analysis. Although there was no strong evidence that the treatment effect was modified by the nature of LUTS at baseline, by who delivered the intervention or by how contact was delivered in the intervention, a post hoc analysis suggests that the treatment effect may have been stronger in the pre-COVID period. No difference was seen between the arms in the proportion of urology referrals or adverse events. In terms of the health economic analysis, from an NHS perspective, costs and quality-adjusted life-years (QALYs) were similar across both trial arms. Compared with the usual-care arm, the intervention arm had slightly lower mean costs (adjusted mean difference of –£29.99, 95% CI –£109.84 to £22.63) and a small gain in QALYs (adjusted mean difference of 0.001, 95% CI –0.011 to 0.014). Two sensitivity analyses adjusting for missing data reversed this finding, reflecting the similar costs and outcomes between the two arms. Overall, the results of the economic evaluation indicate that the costs should not be seen as a limiting factor for the roll-out of the TRIUMPH intervention. Qualitative interviews indicated that many men in both intervention and usual-care arms lived with distressing LUTS for long periods without seeking help. Men tolerated symptoms they portrayed as mundane and inevitable parts of ageing, unworthy of clinical attention, unless severe enough to warrant often unpalatable medication or surgery. Mostly men were unaware that a range of self-management techniques existed and might offer support. In this context, men in the intervention arm strongly welcomed the guidance offered. Men appreciated the accessibility of the booklet, the targeted self-management techniques offered, the interest in their neglected LUTS, the HCP meeting and follow-up contact. Men in the intervention arm reported not only symptom improvement, but also better understanding and a renewed sense of self-efficacy in relation to their symptom management, and an accompanying erosion of the stigma that entangled notions of age, LUTS and inevitable irredeemable bodily decline. Men reported feeling both better able to take action to redress symptoms and more cheerful about their LUTS (and, more broadly, about ageing). Men in the usual-care arm continued to live with distressing symptoms with resigned tolerance. Interviews with both trial participants and GPs in participating practices indicated that self-management guidance for LUTS is currently insufficiently embedded within primary care consultations. Despite describing their contact with primary care positively, men rarely recalled being offered in-depth, structured self-help guidance; men in the usual-care arm remained unfamiliar with the guidance, despite enduring LUTS. Men tended to visit their GP when symptoms were alarming or severe, which may explain why GP encounters often focused on prostate cancer concerns, or moved quickly to medication, forgoing detailed self-management discussions. Most men, and also some GPs, associated pelvic floor exercises with women’s, but not men’s, LUTS. As a result, interviews provided strong grounds for making the intervention guidance routinely available within primary care, to better meet clinical recommendations promoting conservative care for men with LUTS and to better support men’s knowledge and understanding both of their symptoms and of self-management approaches, and to alleviate distressing and neglected symptoms. The strengths of the trial include recruitment to target and excellent follow-up rates, with a clustered trial design to reduce contamination, resulting in informative and robust conclusions. The primary outcome was also intentionally timed to allow the longer-term benefit of the TRIUMPH intervention to be captured, at 12 months post consent, following a 12-week intervention delivery. Sustained benefit was identified, which can be an issue in the longer-term effectiveness of lifestyle and conservative interventions. The limitations of the trial include the necessity of the trial participants being unmasked. In addition, the trial population had only a small number of non-white men, and included only those who had previously sought help from their GP for their LUTS, so may not apply to all men with LUTS. A potential limitation is that sites recruiting to the usual-care arm would potentially have developed renewed awareness of the condition and the current approaches to management as a result of participating in the study. Potentially, this would decrease the observed differences between randomised groups, given that there was some improvement in the usual-care arm in the primary outcome. Conclusions The TRIUMPH intervention showed a sustained benefit for men’s LUTS and quality of life across a range of outcome measures in a UK primary care setting. Although the effect sizes were small, qualitative data showed that men highly valued the intervention. Intervention costs were marginally lower than usual-care costs. The findings show the potential for a short training process to enable nurses or HCA to assess patients and direct them towards appropriate conservative measures in a standardised information booklet. This delivers improved symptoms at low cost, with minimal adverse events. The potential for the same intervention to achieve symptom improvement in incident patients, or for GPs to screen for LUTS to offer the intervention, should be considered. The implications of outcomes in a more diverse population of men need to be evaluated. Trial registration The trial is registered as ISRCTN11669964. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/90/03) and is published in full in Health Technology Assessment; Vol. 28, No. 13. See the NIHR Funding and Awards website for further award information.

Objectives To estimate the cost-effectiveness of a primary care intervention for male lower urinary tract symptoms (LUTS) compared with usual care.Design Economic evaluation alongside a cluster randomised controlled trial from a UK National Health Service (NHS) perspective with a 12-month time horizon.Setting Thirty NHS general practice sites in England.Participants 1077 men aged 18 or older identified in primary care with bothersome LUTS.Interventions A standardised and manualised intervention for the treatment of bothersome LUTS was compared with usual care. The intervention group (n=524) received a standardised information booklet with guidance on conservative treatment for LUTS, urinary symptom assessment and follow-up contacts for 12 weeks. The usual care group (n=553) followed local guidelines between general practice sites.Measures Resource use was obtained from electronic health records, trial staff and participants, and valued using UK reference costs. Quality-adjusted life-years (QALYs) were calculated from the EQ-5D-5L questionnaire. Adjusted mean differences in costs and QALYs and incremental net monetary benefit were estimated.Results 866 of 1077 (80.4%) participants had complete data and were included in the base-case analysis. Over the 12-month follow-up period, intervention and usual care arms had similar mean adjusted costs and QALYs. Mean differences were lower in the intervention arm for adjusted costs −£29.99 (95% CI −£109.84 to £22.63) while higher in the intervention arm for adjusted QALYs 0.001 (95% CI −0.011 to 0.014). The incremental net monetary benefit statistic was £48.01 (95% CI −£225.83 to £321.85) at the National Institute for Health and Care Excellence UK threshold of £20 000 per QALY. The cost-effectiveness acceptability curve showed a 63% probability of the intervention arm being cost-effective at this threshold.Conclusions Costs and QALYs were similar between the two arms at 12 months follow-up. This indicates that the intervention can be implemented in general practice at neutral cost.Trial registration number ISRCTN11669964.

Learning Objectives: We sought to 1) teach the approach to core complaints in EM, 2) teach key skills in EM, 3) de-mystify the process of applying to an EM residency program, and 4) connect students with residents and faculty in the field of EM.Introduction/Background: Despite having a diverse patient population, emergency medicine (EM) remains among the medical specialties with the lowest number of residents and attendings underrepresented in medicine (URiM). Increasing awareness of the field of EM in medical schools that are affiliated with Historically Black Colleges and Universities (HBCUs) is one way to increase the pipeline of URiM in EM. Currently, however, there are zero HBCUs with academic emergency medicine departments. As representatives of four departments of EM, we partnered with one HBCU to attempt to fill this gap for EM-interested students on their 4th year EM home rotation.Educational Objectives: We sought to 1) teach the approach to core complaints in EM, 2) teach key skills in EM, 3) de-mystify the process of applying to an EM residency program, and 4) connect students with residents and faculty in the field of EM.Curricular Design: Educational objectives were developed in conjunction with the faculty advisor to the 4th year EM rotation. We created a 4-week didactic program, with content organized into weekly 4-hour blocks, each led by a different department of EM, on a virtual, interactive platform. Content was mapped and coordinated, pre-reading was assigned and each day included a mix of clinical topics and “advising” sessions.Impact/Effectiveness: A post-curricular survey found universal agreement from students on whether the curriculum was effective in meeting the above goals. Narrative feedback from students highlighted the value of meeting with faculty and residents from different programs, and from going through cases in real time. Informal feedback from supervising faculty at the host-institution was also very positive, particularly in terms of readying students for away rotations. Although our program was targeted towards students at one HBCU, it could be expanded to any medical school without an academic emergency medicine department.

Abstract Background Cognitive behavioural therapy (CBT) is an effective treatment for depression. Self-directed online CBT interventions have made CBT more accessible at a lower cost. However, adherence is often poor and, in the absence of therapist support, effects are modest and short-term. Delivering CBT online using instant messaging is clinically and cost-effective; however, most existing platforms are limited to instant messaging sessions, without the support of between-session “homework” activities. The INTERACT intervention integrates online CBT materials and ‘high-intensity’ therapist-led CBT, delivered remotely in real-time. The INTERACT trial will evaluate this novel integration in terms of clinical and cost-effectiveness, and acceptability to therapists and clients. Methods Pragmatic, two parallel-group multi-centre individually randomised controlled trial, with 434 patients recruited from primary care practices in Bristol, London and York. Participants with depression will be identified via General Practitioner record searches and direct referrals. Inclusion criteria: aged ≥ 18 years; score ≥ 14 on Beck Depression Inventory (BDI-II); meeting International Classification of Diseases (ICD-10) criteria for depression. Exclusion criteria: alcohol or substance dependency in the past year; bipolar disorder; schizophrenia; psychosis; dementia; currently under psychiatric care for depression (including those referred but not yet seen); cannot complete questionnaires unaided or requires an interpreter; currently receiving CBT/other psychotherapy; received high-intensity CBT in the past four years; participating in another intervention trial; unwilling/unable to receive CBT via computer/laptop/smartphone. Eligible participants will be randomised to integrated CBT or usual care. Integrated CBT utilises the standard Beckian intervention for depression and comprises nine live therapist-led sessions, with (up to) a further three if clinically appropriate. The first session is 60–90 min via videocall, with subsequent 50-min sessions delivered online, using instant messaging. Participants allocated integrated CBT can access integrated online CBT resources (worksheets/information sheets/videos) within and between sessions. Outcome assessments at 3-, 6-, 9- and 12-month post-randomisation. The primary outcome is the Beck Depression Inventory (BDI-II) score at 6 months (as a continuous variable). A nested qualitative study and health economic evaluation will be conducted. Discussion If clinically and cost-effective, this model of integrated CBT could be introduced into existing psychological services, increasing access to, and equity of, CBT provision. Trial registration ISRCTN, ISRCTN13112900. Registered on 11/11/2020. Currently recruiting participants. Trial registration data are presented in Table 1.

The sliding clamp PCNA is a key player in eukaryotic genome replication and stability, acting as a platform onto which components of the DNA replication and repair machinery are assembled. Interactions with PCNA are frequently mediated via a short protein sequence motif known as the PCNA-interacting protein (PIP) motif. Here we describe the binding mode of a PIP motif peptide derived from C-terminus of the PolD3 protein from the thermophilic ascomycete fungus C. thermophilum, a subunit of both DNA polymerase δ (Pol δ) and the translesion DNA synthesis polymerase Pol ζ, characterised by isothermal titration calorimetry (ITC) and protein X-ray crystallography. In sharp contrast to the previously determined structure of a Chaetomium thermophilum PolD4 peptide bound to PCNA, binding of the PolD3 peptide is strictly canonical, with the peptide adopting the anticipated 310 helix structure, conserved Gln441 inserting into the so-called Q-pocket on PCNA, and Ile444 and Phe448 forming a two-fork plug that inserts into the hydrophobic surface pocket on PCNA. The binding affinity for the canonical PolD3 PIP-PCNA interaction determined by ITC is broadly similar to that previously determined for the non-canonical PolD4 PIP-PCNA interaction. In addition, we report the structure of a PIP peptide derived from the C. thermophilum Fen1 nuclease bound to PCNA. Like PolD3, Fen1 PIP peptide binding to PCNA is achieved by strictly canonical means. Taken together, these results add to an increasing body of information on how different proteins bind to PCNA, both within and across species.

Abstract Background Adolescence is a developmental period during which youth experience vulnerability to psychopathology. To build the foundation for a parsimonious psychopathology risk calculator while capturing the complexity and dynamic nature of the environment, the current study aimed to identify distinct risk and resilience profiles with a wide range of environmental factors guided by Bronfenbrenner's biopsychosocial ecological system theory. The association between the early‐mid childhood risk profiles and psychopathology in adolescence were examined. Moreover, the predictive utility of early childhood irritability was evaluated in addition to the risk profiles. Methods The data from Future of Families and Child Wellbeing Study a nation‐wide longitudinal study, were used in the latent profile analyses to identify the risk profiles with family, school, and neighborhood characteristics from 3 to 9 years old. To capture the socio‐environmental and cultural nuances, we extracted three subsamples, including Black/African American (n = 2587), Hispanic/Latinx (n = 1577), and White (n = 776) for separate analyses. Risk profile memberships were used to predict adolescence psychopathology, including depression, anxiety, attention deficits, oppositional defiant disorder, and conduct disorder symptoms. The predictive utility of early childhood irritability above and beyond environmental risk profiles was evaluated using stepwise regression. Results Three risk profiles were identified in the Hispanic/Latinx and Black/African American subsamples, while four profiles were identified in White subsample. Almost all risk profile membership predicted both internalizing and externalizing psychopathology, while some profiles are predictive of externalizing symptoms only. Higher level of irritability predicted higher symptomatology in all five mental health outcomes above and beyond the environmental profiles. Conclusions Distinct risk and resilience profiles primarily driven by parent and family characteristics were identified for all three major race/ethnicity groups. Our findings lay the foundation for a more efficient multi‐tiered information gathering process in mental health clinical settings to aid the decision making for intervention and prevention.

Abstract Objectives In light of the youth mental health crisis, as 1 in 5 children have a mental disorder diagnosis by age 3, identification of transdiagnostic behavioral vulnerability prior to impairing psychopathology must occur at an earlier phase of the clinical sequence. Here, we lay the groundwork for a pragmatic irritability measure to identify at‐risk infant‐toddlers. Methods Data comprised N = 350 diverse infant‐toddlers and their mothers assessed at ∼14 months old for irritability (Multidimensional Assessment Profiles‐ Temper Loss‐Infant/Toddler (MAPS‐TL‐IT) and impairment (Early Childhood Irritability‐Related Impairment Interview, E‐CRI; and Family Life Impairment Scale (FLIS). Bimonthly follow‐up surveys assessed impairment (FLIS) over the following year. Results Stepwise logistic regression indicated that 5 MAPS‐TL‐IT items were most informative for differentiating concurrent impairment on the FLIS: “frustrated about small things”; “hit, bite, or kick during tantrums”; “trouble cheering up when grumpy”; “grumpy during fun activities” and “tantrums in public”. With this summed score, Receiver Operating Characteristics analysis differentiating concurrent impairment on the E‐CRI indicated good classification accuracy for (Area under the curve = 0.755, p

Abstract Objectives Characterizing the scope and import of early childhood irritability is essential for real‐world actualization of this reliable indicator of transdiagnostic mental health risk. Thus, we utilize pragmatic assessment to establish prevalence, stability, and predictive utility of clinically significant early childhood irritability. Methods Data included two independent, diverse community samples of preschool age children (N = 1857; N = 1490), with a subset enriched for risk (N = 425) assessed longitudinally from early childhood through preadolescence (∼4–9 years old). A validated, brief (2‐item) scale pragmatically assessed clinically significant irritability. In the longitudinal subsample, clinical interviews assessed internalizing/externalizing disorders. Results One in five preschool‐age children had clinically significant irritability, which was independently replicated. Irritability was highly stable through preadolescence. Children with versus without clinically significant early childhood irritability had greater odds of early onset, persistent internalizing/externalizing disorders. The pragmatic assessment effectively screened out low‐risk children and identified 2/3 of children with early‐onset, persistent psychopathology. Conclusions Clinically significant early childhood irritability prevalence is akin to the pediatric obesity epidemic and may warrant similar universal screening/intervention. Also, irritability's stability demonstrates the common guidance “they'll grow out of it” to be false. Finally, pragmatic irritability assessment has transdiagnostic predictive power and addresses a need for feasible measures to flag risk.

Background Emollients are recommended for children with eczema (atopic eczema/dermatitis). A lack of head-to-head comparisons of the effectiveness and acceptability of the different types of emollients has resulted in a ‘trial and error’ approach to prescribing. Objective To compare the effectiveness and acceptability of four commonly used types of emollients for the treatment of childhood eczema. Design Four group, parallel, individually randomised, superiority randomised clinical trials with a nested qualitative study, completed in 2021. A purposeful sample of parents/children was interviewed at ≈ 4 and ≈ 16 weeks. Setting Primary care (78 general practitioner surgeries) in England. Participants Children aged between 6 months and 12 years with eczema, of at least mild severity, and with no known sensitivity to the study emollients or their constituents. Interventions Study emollients sharing the same characteristics in the four types of lotion, cream, gel or ointment, alongside usual care, and allocated using a web-based randomisation system. Participants were unmasked and the researcher assessing the Eczema Area Severity Index scores was masked. Main outcome measures The primary outcome was Patient-Oriented Eczema Measure scores over 16 weeks. The secondary outcomes were Patient-Oriented Eczema Measure scores over 52 weeks, Eczema Area Severity Index score at 16 weeks, quality of life (Atopic Dermatitis Quality of Life, Child Health Utility-9 Dimensions and EuroQol-5 Dimensions, five-level version, scores), Dermatitis Family Impact and satisfaction levels at 16 weeks. Results A total of 550 children were randomised to receive lotion (analysed for primary outcome 131/allocated 137), cream (137/140), gel (130/135) or ointment (126/138). At baseline, 86.0% of participants were white and 46.4% were female. The median (interquartile range) age was 4 (2–8) years and the median Patient-Oriented Eczema Measure score was 9.3 (SD 5.5). There was no evidence of a difference in mean Patient-Oriented Eczema Measure scores over the first 16 weeks between emollient types (global p = 0.765): adjusted Patient-Oriented Eczema Measure pairwise differences – cream–lotion 0.42 (95% confidence interval –0.48 to 1.32), gel–lotion 0.17 (95% confidence interval –0.75 to 1.09), ointment–lotion –0.01 (95% confidence interval –0.93 to 0.91), gel–cream –0.25 (95% confidence interval –1.15 to 0.65), ointment–cream –0.43 (95% confidence interval –1.34 to 0.48) and ointment–gel –0.18 (95% confidence interval –1.11 to 0.75). There was no effect modification by parent expectation, age, disease severity or the application of UK diagnostic criteria, and no differences between groups in any of the secondary outcomes. Median weekly use of allocated emollient, non-allocated emollient and topical corticosteroids was similar across groups. Overall satisfaction was highest for lotions and gels. There was no difference in the number of adverse reactions and there were no significant adverse events. In the nested qualitative study (n = 44 parents, n = 25 children), opinions about the acceptability of creams and ointments varied most, yet problems with all types were reported. Effectiveness may be favoured over acceptability. Parents preferred pumps and bottles over tubs and reported improved knowledge about, and use of, emollients as a result of taking part in the trial. Limitations Parents and clinicians were unmasked to allocation. The findings may not apply to non-study emollients of the same type or to children from more ethnically diverse backgrounds. Conclusions The four emollient types were equally effective. Satisfaction with the same emollient types varies, with different parents/children favouring different ones. Users need to be able to choose from a range of emollient types to find one that suits them. Future work Future work could focus on how best to support shared decision-making of different emollient types and evaluations of other paraffin-based, non-paraffin and ‘novel’ emollients. Trial registration This trial is registered as ISRCTN84540529 and EudraCT 2017-000688-34. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (HTA 15/130/07) and will be published in full in Health Technology Assessment; Vol. 27, No. 19. See the NIHR Journals Library website for further project information. Plain language summary One in five children in the UK have eczema, a long-term, itchy, dry skin condition. It can significantly affect both the child and their family. Most children are diagnosed and looked after by their family doctor (general practitioner) and are prescribed moisturisers (also called emollients) to relieve skin dryness and other creams (topical corticosteroids) to control flare-ups. However, there are many different types of emollients and, to our knowledge, limited research to show which is better. In the Best Emollients for Eczema clinical trial, we compared the four main types of moisturisers – lotions, creams, gels and ointments. These types vary in their consistency, from thin to thick. We recruited 550 children (most of whom were white and had moderate eczema) and randomly assigned them to use one of the four different types as their main moisturiser for 16 weeks. We found no difference in effectiveness. Parent-reported eczema symptoms, eczema severity and quality of life were the same for all the four types of moisturisers. However, overall satisfaction was highest for lotions and gels. Ointments may need to be used less and cause less stinging. We interviewed 44 parents and 25 children who took part. Opinions of all four types of moisturisers varied. What one family liked about a moisturiser was not necessarily the same for another and preferences were individual to each user. Sometimes there was a tension between how well a moisturiser worked (effectiveness) and how easy it was to use (acceptability). In these cases, effectiveness tended to decide whether or not parents kept using it. People found moisturisers in pumps and bottles easier to use than those in tubs. A number of participants valued the information they were given about how to use moisturisers. Our results suggest that the type of moisturiser matters less than finding one that suits the child and family. Scientific summary Background Eczema (also called atopic eczema/dermatitis) is a common condition that usually first appears in early childhood. It is characterised by dry, itchy skin. Emollients are recommended for all patients, used as a ‘leave-on’ treatment to add and help retain moisture in the skin. For all but the mildest disease, they are used in combination with topical anti-inflammatory (topical corticosteroids or calcineurin inhibitors) to treat and prevent eczema flare-ups. Despite the accepted importance of emollients in treating the dry skin of eczema, there is limited evidence to guide prescribers and users on what types to use. In previous research, parents/carers (hereafter, parents) of children with eczema have spoken of a ‘trial and error’ approach to finding an emollient that suits them and their child, with the attendant frustration, waste and costs to both users and the health service. Objectives We sought to: compare the effectiveness and acceptability of four commonly used types of emollients (lotion, cream, gel and ointment) in the treatment of childhood eczema explore carers’ and children’s experiences of study emollient use and their views about perceived effectiveness and/or acceptability of study emollients. Methods We recruited children with eczema via general practitioners’ (GPs’) surgeries based in three centres (West of England, Wessex and East Midlands). To be eligible, children had to be aged between 6 months and 12 years and to have at least a mild form of disease, and parents had to be willing to be randomly allocated to any of the types as their main emollient. Children with a known sensitivity to study emollients or their constituents were excluded. Participants were randomised to lotion, cream, gel or ointment groups in a 1 : 1 : 1 : 1 manner, stratified by centre and minimised by baseline eczema severity as determined by the Patient Orientated Eczema Measure (POEM) score [mild (3–7 points) vs. moderate/severe (≥ 8 points)] and participant age (< 2 years vs. ≥ 2 years). Participants received their allocated type of emollient via their GP, who prescribed products on their local formulary that were study approved. All study emollients were paraffin based and none contained antimicrobials or urea. Study lotions contained glycerol [Cetraben (Thornton & Ross Ltd, Huddersfield, UK), Diprobase (Bayer UK Ltd, Reading, UK), QV (QV Skincare, Melbourne, VIC, Australia)], study creams had no humectant or lanolin [AproDerm (Fontus Health, Walsall, UK), Aquamax (Intrapharm Laboratories, Maidenhead, UK), Diprobase, Epimax (Aspire Pharma, Petersfield, UK), Zerobase (Thornton & Ross Ltd, Huddersfield, UK)], gels did not contain povidine [AproDerm (Fontus Health, Walsall, UK), Doublebase (Diomed Developments, Hitchin, UK), Isomol (Aspire Pharma, Petersfield, UK), MyriBase (Penlan Healthcare,Weybridge, UK) and Zerodouble (Thornton & Ross Ltd, Huddersfield, UK)] and study ointments had no additives (Diprobase, Emulsifying, Paraffin White soft, Paraffin Yellow soft ointment, White soft/Liquid paraffin 50/50). Participants were asked to use their study emollient as their only leave-on treatment for the first 16 weeks; thereafter, they were free to change. However, if they had problems with or disliked their study emollient, they could stop it and seek an alternative from their GP. Participants’ skin was assessed using the Eczema Area Severity Index (EASI) at baseline and at 16 weeks by a researcher masked to treatment allocation. Other data were collected by self-completed questionnaires weekly (first 16 weeks) and then 4-weekly (until 52 weeks). The primary outcome was eczema symptoms measured using the POEM over 16 weeks. We sought to recruit 520 children to detect a difference of 3.0 points in POEM scores between any two groups with 90% power and a significance level of 0.05, allowing for 20% loss to follow-up and multiple comparison testing. We conducted semistructured interviews with parents and older children at around 4 weeks and 16 weeks after randomisation, sampling on the characteristics of the children. The interviews were conducted face to face and by telephone, informed by a topic guide that was revised during the course of the study. Interviews were audio-recorded and transcribed verbatim. Analysis was thematic and carried out alongside data collection, which stopped once saturation was reached. Ethics approval was granted by the NHS Research Ethics Committee (South West – Central Bristol Research Ethics Committee 17/SW/0089). Results Between January 2018 and October 2019, 78 GP surgeries sent 9437 invitations to potentially eligible children. Expressions of interest were received from 910 parents, and 550 children attended a baseline visit, were eligible and enrolled. At baseline, the characteristics of participants were balanced except for sex, as there were more girls in the cream group (55%) than in the gel group (40%). Most children were white (86.0%), with a median age of 4 years (interquartile range 2–8 years) and moderate severity eczema (mean POEM score 9.32 points; standard deviation 5.46 points). Creams (94.5%) were most likely to have been used before, followed by ointments (66%), lotions (63.0%) and gels (25.0%). Participants were randomised to receive lotion (n = 137), cream (n = 140), gel (n = 135) or ointment (n = 138), with prescriptions issued by their GP. The median number of days between randomisation and reported first use of emollient was 4 days (interquartile range 3–7 days), with 80% reporting first use within 7 days of randomisation. There were 29 withdrawals (24 in the first 16 weeks). A total of 95% of participants provided at least one post-baseline POEM score and, therefore, were included in the primary outcome analysis. The researcher undertaking the EASI assessment identified the correct allocation in seven participants. There was no difference in the primary outcome (repeated-measures analysis of weekly POEM scores over the first 16 weeks) between the different groups (global p = 0.765). The adjusted differences in mean POEM scores [95% confidence interval (CI)] for pairwise comparisons were as follows: lotion versus cream 0.42 (95% CI –0.48 to 1.32; p = 0.360); lotion versus gel 0.17 (95% CI –0.75 to 1.09; p = 0.718); lotion versus ointment –0.01 (95% CI –0.93 to 0.91; p = 0.983); cream versus gel –0.25 (95% CI –1.15 to 0.65; p = 0.586); cream versus ointment –0.43 (95% CI –1.34 to 0.48; p = 0.354); and gel versus ointment –0.18 (95% CI –1.11 to 0.75; p = 0.704). Adjusting for sex imbalance at baseline and imputing missing data using multiple imputation did not meaningfully alter these results. There was no evidence of a difference in mean POEM scores between treatment groups or in any of the pairwise comparisons in first 16 weeks in ‘per-protocol’ analysis (p = 0.238) or over the 52 weeks (p = 0.909). There was no evidence of effect modification in prespecified subgroup analyses by parent prior emollient expectation (p = 0.935), participant age (p = 0.343), participant eczema severity (p = 0.042), or UK diagnostic criteria for atopic dermatitis (p = 0.291). No differences between groups were seen in the following secondary outcomes at 16 weeks (or 52 weeks, if also collected): EASI scores, Atopic Dermatitis Quality of Life scores, Child Health Utility 9-Dimension scores, Dermatitis Family Impact scores and well-controlled weeks. During the first 16 weeks, median reported weekly use of the allocated emollient appeared to be higher in the lotion and cream groups (6 days per week) and lower in the gel (5 days) and ointment (3 days) groups, but this difference in usage was not statistically significant (p = 0.481). Similarly, there was no difference between groups in median reported daily use of non-allocated emollient or topical corticosteroids. Overall satisfaction was highest with lotions and gels (67.3% and 64.5% very or mostly satisfied, respectively) and dissatisfaction was highest with creams and ointments (34.2% and 40.4% dissatisfied or very dissatisfied, respectively) (p = 0.003). Overall, 37% of participants reported at least one adverse reaction, the most common being ‘application site reactions’ (e.g. worsening of eczema). There was no evidence that the proportion of children reporting adverse reactions in the first 16 weeks of follow-up differed by treatment group (p = 0.794). There were no significant adverse events. In the nested qualitative study, 44 parents were interviewed, 20 at both weeks 4 and 24 (including five repeat interviews at week 16). Children took part in 25 interviews. Participants judged the effectiveness of study emollients by comparing them with others they had used in the past (i.e. the perceived hydrating action of the emollient, skin feel after application, skin symptoms and appearance, the number of flare-ups, and the need for topical corticosteroid use). Other factors identified as affecting effectiveness were weather and the frequency and quantity of emollient application. Acceptability was usually considered alongside or as part of the effectiveness of an emollient. Characteristics of the emollients that participants considered were how it felt on the skin, ease of application and absorbency, with smell being less important. In terms of containers, participants favoured pumps and squeezer bottles for practical reasons, including older child being able to self-apply. Many participants in the lotion and gel groups reported ease of application but felt that these types of emollients had to be used more often, and there was a perception that they ‘maintained’ rather than improved the skin. Although participants using study creams and study ointment were more likely to report improvements, opinions about their acceptability were more divergent. Problems were reported with all types of emollients. At 16 weeks, there was no clear pattern or differentiation between the emollient types in terms of continued use over and above the factors listed above. Parents of children with very dry and/or rough skin tended to prefer an emollient with a thicker consistency, such as a cream or an ointment. Age was also reported to influence emollient use: application may be easier/more frequent in younger children, accompanying nappy changes, and more difficult in older children as they become more independent and attend school. Some participants thought that their child’s eczema and the effectiveness of their emollient was related to their ethnicity. Changes in behaviour and knowledge were reported as a result of taking part in the trial. For some, the regular study questionnaires had reminded them to apply their emollient regularly. Others reported persisting more with one treatment or that the emollient information sheet had improved their knowledge of eczema management. Conclusions No one type of emollient was found to be superior, although these findings may not apply to children from more ethnically diverse backgrounds. Parents and children should be made aware that application site reactions are common; persistence may be required to find an emollient that works for them; and preferences may change with time, season and body site. We have also demonstrated the need for choice and education around the use of emollients for the treatment of eczema in children. Without this, emollients may be applied incorrectly or not as frequently as prescribed. Most children with eczema will need, in addition to their emollient, a topical anti-inflammatory treatment (usually corticosteroids) appropriate to the site and severity of their eczema to get, and keep, control of their condition. Guidelines should advocate for, and formularies support, a range of emollients, with lotions, creams, gels and ointments all available. Prescribers and pharmacists have an important role in ensuring that families are aware of the different emollients available, to support them in selecting a type most likely to suit them and to advise on optimal use. Verbal advice could be accompanied by written or online information (including videos) on the role of emollients and how to use them, perhaps accompanied by a planned review at the end of an agreed trial period. Future research could evaluate a decision aid to support parents and clinicians in deciding which type of emollient to try first and the clinical effectiveness and cost-effectiveness of providing ‘tester pots’ of each type of emollient to try before selecting their preferred emollient. Further trials may be appropriate to compare emollients in more ethnically diverse populations and of different types not evaluated in this study, for example ointments with emulsifiers and humectant-containing, plant-based and ‘novel’ emollients, including those designed to alter the skin microbiome. Research in this field would benefit from an internationally agreed system of classifying different emollients and a common approach to measuring and reporting treatment use. Finally, further research is needed to determine how emollients best fit into an overall package of eczema care, which includes frequency of use, bathing, use of other topical treatments and avoidance of triggers. Trial registration This trial is registered as ISRCTN84540529 and EudraCT 2017-000688-34. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (HTA 15/130/07) and will be published in full in Health Technology Assessment; Vol. 27, No. 19. See the NIHR Journals Library website for further project information.

Abstract Background Stroke is a significant contributor of worldwide disability and morbidity with substantial economic consequences. Rehabilitation is a vital component of stroke recovery, but inpatient stroke rehabilitation programs can struggle to meet the recommended hours of therapy per day outlined by the Canadian Stroke Best Practices and American Heart Association. Mobile applications (apps) are an emerging technology which may help bridge this deficit, however this area is understudied. The purpose of this study is to review the effect of mobile apps for stroke rehabilitation on stroke impairments and functional outcomes. Specifically, this paper will delve into the impact of varying mobile app types on stroke rehabilitation. Methods This systematic review included 29 studies: 11 randomized control trials and 18 quasi-experimental studies. Data extrapolation mapped 5 mobile app types (therapy apps, education apps, rehab videos, reminders, and a combination of rehab videos with reminders) to stroke deficits (motor paresis, aphasia, neglect), adherence to exercise, activities of daily living (ADLs), quality of life, secondary stroke prevention, and depression and anxiety. Results There were multiple studies supporting the use of therapy apps for motor paresis or aphasia, rehab videos for exercise adherence, and reminders for exercise adherence. For permutations involving other app types with stroke deficits or functional outcomes (adherence to exercise, ADLs, quality of life, secondary stroke prevention, depression and anxiety), the results were either non-significant or limited by a paucity of studies. Conclusion Mobile apps demonstrate potential to assist with stroke recovery and augment face to face rehabilitation, however, development of a mobile app should be carefully planned when targeting specific stroke deficits or functional outcomes. This study found that mobile app types which mimicked principles of effective face-to-face therapy (massed practice, task-specific practice, goal-oriented practice, multisensory stimulation, rhythmic cueing, feedback, social interaction, and constraint-induced therapy) and education (interactivity, feedback, repetition, practice exercises, social learning) had the greatest benefits. Protocol registration PROPSERO (ID CRD42021186534). Registered 21 February 2021

Abstract Background The UK’s living-donor kidney transplant (LDKT) activity falls behind that of many other countries internationally, with less than 20% of those eligible receiving a LDKT each year. Certain individuals with kidney disease in the UK appear to be particularly disadvantaged in accessing a LDKT; the most socioeconomically deprived people with kidney disease are 60% less likely to receive a LDKT than the least deprived. Improving equity in living-donor kidney transplantation has been highlighted as an international research priority. Methods This feasibility trial was designed to determine the feasibility of delivery and acceptability of a multicomponent intervention designed to improve access to living-donor kidney transplantation. The intervention comprises three main components: (i) a meeting between a home educator and the transplant candidate for a dedicated discussion about living-donor kidney transplantation, living kidney donation and potential donors; (ii) a standardized letter from a healthcare professional to a candidate’s potential donors and (iii) a home-based education and family engagement session including two home educators, the transplant candidate and their family. The primary objectives are to establish the feasibility (i) of delivering the developed intervention in existing care pathways and (ii) of undertaking a randomised controlled trial of the intervention. A mixed-methods parallel process evaluation will investigate the acceptability, implementation and mechanisms of impact of the intervention. The trial is based at two UK hospitals: a transplanting hospital and a non-transplanting referral hospital. Individuals are eligible if they are ≥ 18 years old, are active on the kidney transplant waiting list or have been referred for transplant listing and do not have a potential living-donor undergoing surgical assessment. Randomisation will be undertaken with concealed allocation. Participants will be randomly allocated 1:1 to (i) the intervention or (ii) usual care, stratified by site to ensure a balance in terms of local differences. Minimisation will be used to ensure balance in sex, age group and socioeconomic strata, with probability weighting of 0.8 in order to reduce predictability. The primary outcomes are recruitment (% of those eligible and invited who consent to randomisation) and retention (% of participants completing follow-up). Discussion Findings will inform the design of a future fully powered, randomised controlled trial to formally evaluate the effectiveness of the intervention at improving equitable access to living-donor kidney transplantation. Trial registration ISRCTN Registry ISRCTN10989132 Applied 30/10/20.

This scoping review explores current practices for obtaining consent in research on risky behaviours among adolescents in Canada. The JBI methodology for scoping reviews was used. The database search was conducted in August 2021 and updated in November 2022. Papers published in 2010 or later were included. Extracted data included study characteristics, sample characteristics, and consent procedures. The review included 83 reports covering 57 studies. Nearly 60% of studies relied on adolescent self-consent for participation. Adolescent self-consent was more common than parental/guardian consent for studies using in-person research methods, older adolescent groups, and particularly vulnerable populations. Parental/guardian consent was more common for studies using younger age groups and general population samples. Adolescent self-consent was more common than parental/guardian consent for most risky behaviours covered by this review. These results provide insight into current consent practices in this area and offer guidance to researchers and institutional review boards in Canada. [ABSTRACT FROM AUTHOR]