Effects of an Increased Financial Incentive on Follow-up in an Online, Automated Smoking Cessation Trial: A randomized Controlled Study Within a Trial.

INTRODUCTION: Poor retention in clinical trials can impact on statistical power, reliability, validity, and generalizability of findings and is a particular challenge in smoking cessation studies. In online trials with automated follow-up mechanisms, poor response also increases the resource need for manual follow-up. This study compared two financial incentives on response rates at 6 months follow up, in an online, automated smoking cessation feasibility trial of a cessation smartphone app (Quit Sense). AIMS AND METHODS: A study within a trial (SWAT), embedded within a host randomized controlled trial. Host trial participants were randomized 1:1 to receive either a £10 or £20 voucher incentive, for completing the 6-month questionnaire. Stratification for randomization to the SWAT was by minimization to ensure an even split of host trial arm participants and by 6-week response rate. Outcome measures were: Questionnaire completion rate, time to completion, number of completers requiring manual follow-up, and completeness of responses. RESULTS: Two hundred and four participants were randomized to the SWAT. The £20 and £10 incentives did not differ in completion rate at 6 months (79% vs. 74%; p = .362) but did reduce the proportion of participants requiring manual follow-up (46% vs. 62%; p = .018) and the median completion time (7 days vs. 15 days; p = .008). Measure response completeness rates were higher among £20 incentive participants, though differences were small for the host trial's primary smoking outcome. CONCLUSIONS: Benefits to using relatively modest increases in incentive for online smoking cessation trials include more rapid completion of follow-up questionnaires and reduced manual follow-up. IMPLICATIONS: A modest increase in incentive (from £10 to £20) to promote the completion of follow-up questionnaires in online smoking cessation trials may not increase overall response rates but could lead to more rapid data collection, a reduced need for manual follow-up and reduced missing data among those who initiate completing a questionnaire. Such an improvement may help to reduce bias, increase validity and generalizability, and improve statistical power in smoking cessation trials. TRIAL REGISTRATION: Host trial ISRCTN12326962, SWAT repository store ID 164.

An Automated, Online Feasibility Randomized Controlled Trial of a Just-In-Time Adaptive Intervention for Smoking Cessation (Quit Sense).

INTRODUCTION: Learned smoking cues from a smoker's environment are a major cause of lapse and relapse. Quit Sense, a theory-guided Just-In-Time Adaptive Intervention smartphone app, aims to help smokers learn about their situational smoking cues and provide in-the-moment support to help manage these when quitting. METHODS: A two-arm feasibility randomized controlled trial (N = 209) to estimate parameters to inform a definitive evaluation. Smoker's willing to make a quit attempt were recruited using online paid-for adverts and randomized to "usual care" (text message referral to NHS SmokeFree website) or "usual care" plus a text message invitation to install Quit Sense. Procedures, excluding manual follow-up for nonresponders, were automated. Follow-up at 6 weeks and 6 months included feasibility, intervention engagement, smoking-related, and economic outcomes. Abstinence was verified using cotinine assessment from posted saliva samples. RESULTS: Self-reported smoking outcome completion rates at 6 months were 77% (95% CI 71%, 82%), viable saliva sample return rate was 39% (95% CI 24%, 54%), and health economic data 70% (95% CI 64%, 77%). Among Quit Sense participants, 75% (95% CI 67%, 83%) installed the app and set a quit date and, of those, 51% engaged for more than one week. The 6-month biochemically verified sustained abstinence rate (anticipated primary outcome for definitive trial), was 11.5% (12/104) among Quit Sense participants and 2.9% (3/105) for usual care (adjusted odds ratio = 4.57, 95% CIs 1.23, 16.94). No evidence of between-group differences in hypothesized mechanisms of action was found. CONCLUSIONS: Evaluation feasibility was demonstrated alongside evidence supporting the effectiveness potential of Quit Sense. IMPLICATIONS: Running a primarily automated trial to initially evaluate Quit Sense was feasible, resulting in modest recruitment costs and researcher time, and high trial engagement. When invited, as part of trial participation, to install a smoking cessation app, most participants are likely to do so, and, for those using Quit Sense, an estimated one-half will engage with it for more than 1 week. Evidence that Quit Sense may increase verified abstinence at 6-month follow-up, relative to usual care, was generated, although low saliva return rates to verify smoking status contributed to considerable imprecision in the effect size estimate.

Clinical and cost-effectiveness of social recovery therapy for the prevention and treatment of long-term social disability among young people with emerging severe mental illness (PRODIGY): randomised controlled trial.

BACKGROUND: Young people with social disability and severe and complex mental health problems have poor outcomes, frequently struggling with treatment access and engagement. Outcomes may be improved by enhancing care and providing targeted psychological or psychosocial intervention. AIMS: We aimed to test the hypothesis that adding social recovery therapy (SRT) to enhanced standard care (ESC) would improve social recovery compared with ESC alone. METHOD: A pragmatic, assessor-masked, randomised controlled trial (PRODIGY: ISRCTN47998710) was conducted in three UK centres. Participants (n = 270) were aged 16-25 years, with persistent social disability, defined as under 30 hours of structured activity per week, social impairment for at least 6 months and severe and complex mental health problems. Participants were randomised to ESC alone or SRT plus ESC. SRT was an individual psychosocial therapy delivered over 9 months. The primary outcome was time spent in structured activity 15 months post-randomisation. RESULTS: We randomised 132 participants to SRT plus ESC and 138 to ESC alone. Mean weekly hours in structured activity at 15 months increased by 11.1 h for SRT plus ESC (mean 22.4, s.d. = 21.4) and 16.6 h for ESC alone (mean 27.7, s.d. = 26.5). There was no significant difference between arms; treatment effect was -4.44 (95% CI -10.19 to 1.31, P = 0.13). Missingness was consistently greater in the ESC alone arm. CONCLUSIONS: We found no evidence for the superiority of SRT as an adjunct to ESC. Participants in both arms made large, clinically significant improvements on all outcomes. When providing comprehensive evidence-based standard care, there are no additional gains by providing specialised SRT. Optimising standard care to ensure targeted delivery of existing interventions may further improve outcomes.

Impact of cachexia on outcomes in aggressive lymphomas.

Cancer cachexia is defined as a state of involuntary weight loss, attributed to altered body composition with muscle mass loss and/or loss of adiposity. Identifying the association between cancer cachexia and outcomes may pave the way for novel agents that target the cancer cachexia process. Clinical parameters for measurement of cancer cachexia are needed. We conducted a single-institution retrospective analysis that included 86 NHL patients with the aim of identifying an association between cancer cachexia and outcomes in aggressive lymphomas using the cachexia index (CXI) suggested by Jafri et al. (Clin Med Insights Oncol 9:87-93, 15). Impact of cachexia factors on progression-free survival (PFS) and overall survival (OS) were assessed using log-rank test and Cox proportional hazards regression. Patients were dichotomized around the median CXI into "non-cachectic" (CXI ≥49.8, n = 41) and "cachectic" (CXI <49.8, n = 40) groups. Cachectic patients had significantly worse PFS (HR 2.18, p = 0.044) and OS (HR = 4.05, p = 0.004) than non-cachectic patients. Cachexia as defined by the CXI is prognostic in aggressive lymphomas and implies that novel therapeutic strategies directed at reversing cachexia may improve survival in this population.

Cluster Analysis to Identify Clinical Subtypes of Ménière's Disease.

OBJECTIVE: To identify distinct clinical subtypes of Ménière's disease by analyzing data acquired from a UK registry of patients who have been diagnosed with Ménière's disease. STUDY DESIGN: Observational study. METHODS: Patients with Ménière's disease were identified at secondary/tertiary care clinics. Cluster analysis was performed by grouping participants sharing similar characteristics and risk factors into groups based on a defined measure of similarity. RESULTS: A total of 411 participants were recruited into this study. Two main clusters were identified: participants diagnosed with ear infections (OR = 0.30, p < 0.014, 95% CI: 0.11-0.78) were more likely to be allocated in Cluster 1 (C1). Participants reporting tinnitus in both ears (OR = 11.89, p < 0.001, 95% CI: 4.08-34.64), low pitched tinnitus (OR = 21.09, p < 0.001, 95% CI: 7.47-59.54), and those reporting stress as a trigger for vertigo attacks (OR = 14.94, p < 0.001, 95% CI: 4.54-49.10) were significantly more likely to be in Cluster 2 (C2). Also, participants diagnosed with Benign Paroxysmal Positional Vertigo (OR = 13.14, <0.001, 95% CI: 4.35-39.74), autoimmune disease (OR = 5.97, p < 0.007, 95% CI: 1.62-22.03), depression (OR = 4.72, p < 0.056, 95% CI: 0.96-23.24), migraines (OR = 3.13, p < 0.008, 95% CI: 1.34-7.26), drug allergy (OR = 3.25, p < 0.029, 95% CI: 1.13-9.34), and hay fever (OR = 3.12, p < 0.009, 95% CI: 1.33-7.34) were significantly more likely to be clustered in C2. CONCLUSIONS: This study supports the hypothesis that Ménière's disease is a heterogeneous condition with subgroups that may be identifiable by clinical features. Two main clusters were identified with differing putative etiological factors. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3286-3292, 2024.

A smoking cessation smartphone app that delivers real-time 'context aware' behavioural support: the Quit Sense feasibility RCT.

Background: During a quit attempt, cues from a smoker's environment are a major cause of brief smoking lapses, which increase the risk of relapse. Quit Sense is a theory-guided Just-In-Time Adaptive Intervention smartphone app, providing smokers with the means to learn about their environmental smoking cues and provides 'in the moment' support to help them manage these during a quit attempt. Objective: To undertake a feasibility randomised controlled trial to estimate key parameters to inform a definitive randomised controlled trial of Quit Sense. Design: A parallel, two-arm randomised controlled trial with a qualitative process evaluation and a 'Study Within A Trial' evaluating incentives on attrition. The research team were blind to allocation except for the study statistician, database developers and lead researcher. Participants were not blind to allocation. Setting: Online with recruitment, enrolment, randomisation and data collection (excluding manual telephone follow-up) automated through the study website. Participants: Smokers (323 screened, 297 eligible, 209 enrolled) recruited via online adverts on Google search, Facebook and Instagram. Interventions: Participants were allocated to 'usual care' arm (n = 105; text message referral to the National Health Service SmokeFree website) or 'usual care' plus Quit Sense (n = 104), via a text message invitation to install the Quit Sense app. Main outcome measures: Follow-up at 6 weeks and 6 months post enrolment was undertaken by automated text messages with an online questionnaire link and, for non-responders, by telephone. Definitive trial progression criteria were met if a priori thresholds were included in or lower than the 95% confidence interval of the estimate. Measures included health economic and outcome data completion rates (progression criterion #1 threshold: ≥ 70%), including biochemical validation rates (progression criterion #2 threshold: ≥ 70%), recruitment costs, app installation (progression criterion #3 threshold: ≥ 70%) and engagement rates (progression criterion #4 threshold: ≥ 60%), biochemically verified 6-month abstinence and hypothesised mechanisms of action and participant views of the app (qualitative). Results: Self-reported smoking outcome completion rates were 77% (95% confidence interval 71% to 82%) and health economic data (resource use and quality of life) 70% (95% CI 64% to 77%) at 6 months. Return rate of viable saliva samples for abstinence verification was 39% (95% CI 24% to 54%). The per-participant recruitment cost was £19.20, which included advert (£5.82) and running costs (£13.38). In the Quit Sense arm, 75% (95% CI 67% to 83%; 78/104) installed the app and, of these, 100% set a quit date within the app and 51% engaged with it for more than 1 week. The rate of 6-month biochemically verified sustained abstinence, which we anticipated would be used as a primary outcome in a future study, was 11.5% (12/104) in the Quit Sense arm and 2.9% (3/105) in the usual care arm (estimated effect size: adjusted odds ratio = 4.57, 95% CIs 1.23 to 16.94). There was no evidence of between-arm differences in hypothesised mechanisms of action. Three out of four progression criteria were met. The Study Within A Trial analysis found a £20 versus £10 incentive did not significantly increase follow-up rates though reduced the need for manual follow-up and increased response speed. The process evaluation identified several potential pathways to abstinence for Quit Sense, factors which led to disengagement with the app, and app improvement suggestions. Limitations: Biochemical validation rates were lower than anticipated and imbalanced between arms. COVID-19-related restrictions likely limited opportunities for Quit Sense to provide location tailored support. Conclusions: The trial design and procedures demonstrated feasibility and evidence was generated supporting the efficacy potential of Quit Sense. Future work: Progression to a definitive trial is warranted providing improved biochemical validation rates. Trial registration: This trial is registered as ISRCTN12326962. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (NIHR award ref: 17/92/31) and is published in full in Public Health Research; Vol. 12, No. 4. See the NIHR Funding and Awards website for further award information.

Smokers often fail to quit because of urges to smoke triggered by their surroundings (e.g. being around smokers). We developed a smartphone app ('Quit Sense') which learns about an individual's surroundings and locations where they smoke. During a quit attempt, Quit Sense uses in-built sensors to identify when smokers are in those locations and sends 'in the moment' advice to help prevent them from smoking. We ran a feasibility study to help plan for a future large study to see if Quit Sense helps smokers to quit. This feasibility study was designed to tell us how many participants complete study measures; recruitment costs; how many participants install and use Quit Sense; and estimate whether Quit Sense may help smokers to stop and how it might do this. We recruited 209 smokers using online adverts on Google search, Facebook and Instagram, costing £19 per participant. Participants then had an equal chance of receiving a web link to the National Health Service SmokeFree website ('usual care group') or receive that same web link plus a link to the Quit Sense app ('Quit Sense group'). Three-quarters of the Quit Sense group installed the app on their phone and half of these used the app for more than 1 week. We followed up 77% of participants at 6 months to collect study data, though only 39% of quitters returned a saliva sample for abstinence verification. At 6 months, more people in the Quit Sense group had stopped smoking (12%) than the usual care group (3%). It was not clear how the app helped smokers to quit based on study measures, though interviews found that the process of training the app helped people quit through learning about what triggered their smoking behaviour. The findings support undertaking a large study to tell us whether Quit Sense really does help smokers to quit.

Risk Factors for the Development of Bilateral Ménière's Disease.

OBJECTIVE: To identify key risk factors for the development of bilateral Ménière's disease. STUDY DESIGNS: Observational study. SETTING: Four NHS Trusts and four independent hospitals or clinics, within three distinct urban and rural regions within the United Kingdom (Norfolk, Leicestershire, and London). METHODS: Patients with Ménière's disease were identified at ENT or audiovestibular medicine secondary/tertiary care and specialist private clinics. A range of patient-reported data, questionnaire data, and clinical data (audiometric, radiological, and specialist balance testing data) was inputted into a bespoke database. A logistic regression model was used to identify potential risk factors for bilateral Ménière's disease compared with unilateral Ménière's disease. RESULTS: A total of 411 participants were recruited into this study, 263 from NHS Trusts and 148 from independent hospitals or clinics. In our cohort of patients, 22% of individuals were identified as having bilateral Ménière's disease. Two statistically significant independent variables were identified as risk factors for the development of bilateral Ménière's disease: the presence of psoriasis and a history of ear infections. CONCLUSIONS: Psoriasis and a history of ear infection have been identified as key risk factors for the development of bilateral Ménière's disease. It is anticipated that further work based on this finding will allow a better understanding of the underlying pathophysiological mechanisms that predispose to the development of Ménière's disease symptoms.

Hospital-based caregiver intervention for people following hip fracture surgery (HIP HELPER): multicentre randomised controlled feasibility trial with embedded qualitative study in England.

OBJECTIVES: To assess the feasibility of conducting a pragmatic, multicentre randomised controlled trial (RCT) to test the clinical and cost-effectiveness of an informal caregiver training programme to support the recovery of people following hip fracture surgery. DESIGN: Two-arm, multicentre, pragmatic, open, feasibility RCT with embedded qualitative study. SETTING: National Health Service (NHS) providers in five English hospitals. PARTICIPANTS: Community-dwelling adults, aged 60 years and over, who undergo hip fracture surgery and their informal caregivers. INTERVENTION: Usual care: usual NHS care. EXPERIMENTAL: usual NHS care plus a caregiver-patient dyad training programme (HIP HELPER). This programme comprised three, 1 hour, one-to-one training sessions for a patient and caregiver, delivered by a nurse, physiotherapist or occupational therapist in the hospital setting predischarge. After discharge, patients and caregivers were supported through three telephone coaching sessions. RANDOMISATION AND BLINDING: Central randomisation was computer generated (1:1), stratified by hospital and level of patient cognitive impairment. There was no blinding. MAIN OUTCOME MEASURES: Data collected at baseline and 4 months post randomisation included: screening logs, intervention logs, fidelity checklists, acceptability data and clinical outcomes. Interviews were conducted with a subset of participants and health professionals. RESULTS: 102 participants were enrolled (51 patients; 51 caregivers). Thirty-nine per cent (515/1311) of patients screened were eligible. Eleven per cent (56/515) of eligible patients consented to be randomised. Forty-eight per cent (12/25) of the intervention group reached compliance to their allocated intervention. There was no evidence of treatment contamination. Qualitative data demonstrated the trial and HIP HELPER programme was acceptable. CONCLUSIONS: The HIP HELPER programme was acceptable to patient-caregiver dyads and health professionals. The COVID-19 pandemic impacting on site's ability to deliver the research. Modifications are necessary to the design for a viable definitive RCT. TRIAL REGISTRATION NUMBER: ISRCTN13270387.

Evaluation of effectiveness and safety of pharmacist independent prescribers in care homes: cluster randomised controlled trial.

OBJECTIVE: To estimate the effectiveness, cost effectiveness (to be reported elsewhere), and safety of pharmacy independent prescribers in care homes. DESIGN: Cluster randomised controlled trial, with clusters based on triads of a pharmacist independent prescriber, a general practice, and one to three associated care homes. SETTING: Care homes across England, Scotland, and Northern Ireland, their associated general practices, and pharmacy independent prescribers, formed into triads. PARTICIPANTS: 49 triads and 882 residents were randomised. Participants were care home residents, aged ≥65 years, taking at least one prescribed drug, recruited to 20 residents/triad. INTERVENTION: Each pharmacy independent prescriber provided pharmaceutical care to approximately 20 residents across one to three care homes, with weekly visits over six months. Pharmacy independent prescribers developed a pharmaceutical care plan for each resident, did medicines reviews/reconciliation, trained staff, and supported with medicines related procedures, deprescribing, and authorisation of prescriptions. Participants in the control group received usual care. MAIN OUTCOMES MEASURES: The primary outcome was fall rate/person at six months analysed by intention to treat, adjusted for prognostic variables. Secondary outcomes included quality of life (EQ-5D by proxy), Barthel score, Drug Burden Index, hospital admissions, and mortality. Assuming a 21% reduction in falls, 880 residents were needed, allowing for 20% attrition. RESULTS: The average age of participants at study entry was 85 years; 70% were female. 697 falls (1.55 per resident) were recorded in the intervention group and 538 falls (1.26 per resident) in the control group at six months. The fall rate risk ratio for the intervention group compared with the control group was not significant (0.91, 95% confidence interval 0.66 to 1.26) after adjustment for all model covariates. Secondary outcomes were not significantly different between groups, with exception of the Drug Burden Index, which significantly favoured the intervention. A third (185/566; 32.7%) of pharmacy independent prescriber interventions involved medicines associated with falls. No adverse events or safety concerns were identified. CONCLUSIONS: Change in the primary outcome of falls was not significant. Limiting follow-up to six months combined with a small proportion of interventions predicted to affect falls may explain this. A significant reduction in the Drug Burden Index was realised and would be predicted to yield future clinical benefits for patients. This large trial of an intensive weekly pharmacist intervention with care home residents was also found to be safe and well received. TRIAL REGISTRATION: ISRCTN 17847169.

prdm1a and olig4 act downstream of Notch signaling to regulate cell fate at the neural plate border.

The zinc finger domain transcription factor prdm1a plays an integral role in the development of the neural plate border cell fates, including neural crest cells and Rohon-Beard (RB) sensory neurons. However, the mechanisms underlying prdm1a function in cell fate specification is unknown. Here, we test more directly how prdm1a functions in this cell fate decision. Rather than affecting cell death or proliferation at the neural plate border, prdm1a acts explicitly on cell fate specification by counteracting olig4 expression in the neighboring interneuron domain. olig4 expression is expanded in prdm1a mutants and olig4 knockdown can rescue the reduced or abrogated neural crest and RB neuron phenotype in prdm1a mutants, suggesting a permissive role for prdm1a in neural plate border-derived cell fates. In addition, prdm1a expression is upregulated in the absence of Notch function, and inhibiting Notch signaling fails to rescue prdm1a mutants. This suggests that prdm1a functions downstream of Notch in the regulation of cell fate at the neural plate border and that Notch regulates the total number of progenitor cells at the neural plate border.

Informed substitution of hazardous chemicals through the lens of California's Safer Consumer Products Alternatives Analysis: Best practices, challenges, and opportunities.

California adopted the Safer Consumer Products (SCP) regulations in 2013, which mandate that companies that manufacture specific products containing designated chemicals of concern complete an Alternatives Analysis. Alternatives Analysis is a process to avoid regrettable substitution by identifying, comparing, and selecting safer alternatives based on technical functions, hazards, exposure pathways, life-cycle multimedia impacts, and economic impacts. The SCP Alternatives Analysis builds upon and expands existing frameworks for alternatives assessments (AAs). The aim of this study was to identify practices from AA that facilitate the robust assessment of alternatives and that align with SCP requirements and identify gaps in the practice. We evaluated completed AAs for methods regarding transparency and careful documentation of information sources, data gaps, uncertainty, criteria, and justification for decision-making. The AAs in this review demonstrate some of the challenges in the field. Most AAs have a constrained scope and only consider chemical substitutes rather than a broad array of functional alternatives. Their scopes were also limited in the hazard endpoints that were evaluated. This was most noted with ecotoxicity endpoints, which were generally confined to aquatic toxicity. The majority of AAs do not explicitly explain their decision-making methods or adequately discuss tradeoffs across the adverse impacts. The AAs also lack the analysis in the exposure, life-cycle impacts, and economic impacts that are required in the SCP Alternatives Analysis process. Further, we recommend strategies and research opportunities to address these challenges and strengthen the practice of AAs. Integr Environ Assess Manag 2022;18:1007-1019. © 2021 SETAC.

Social recovery therapy for young people with emerging severe mental illness: the Prodigy RCT.

BACKGROUND: Young people with social disability and non-psychotic severe and complex mental health problems are an important group. Without intervention, their social problems can persist and have large economic and personal costs. Thus, more effective evidence-based interventions are needed. Social recovery therapy is an individual therapy incorporating cognitive-behavioural techniques to increase structured activity as guided by the participant's goals. OBJECTIVE: This trial aimed to test whether or not social recovery therapy provided as an adjunct to enhanced standard care over 9 months is superior to enhanced standard care alone. Enhanced standard care aimed to provide an optimal combination of existing evidence-based interventions. DESIGN: A pragmatic, single-blind, superiority randomised controlled trial was conducted in three UK centres: Sussex, Manchester and East Anglia. Participants were aged 16-25 years with persistent social disability, defined as < 30 hours per week of structured activity with social impairment for at least 6 months. Additionally, participants had severe and complex mental health problems, defined as at-risk mental states for psychosis or non-psychotic severe and complex mental health problems indicated by a Global Assessment of Functioning score ≤ 50 persisting for ≥ 6 months. Two hundred and seventy participants were randomised 1 : 1 to either enhanced standard care plus social recovery therapy or enhanced standard care alone. The primary outcome was weekly hours spent in structured activity at 15 months post randomisation. Secondary outcomes included subthreshold psychotic, negative and mood symptoms. Outcomes were collected at 9 and 15 months post randomisation, with maintenance assessed at 24 months. RESULTS: The addition of social recovery therapy did not significantly increase weekly hours in structured activity at 15 months (primary outcome treatment effect -4.44, 95% confidence interval -10.19 to 1.31). We found no evidence of significant differences between conditions in secondary outcomes at 15 months: Social Anxiety Interaction Scale treatment effect -0.45, 95% confidence interval -4.84 to 3.95; Beck Depression Inventory-II treatment effect -0.32, 95% confidence interval -4.06 to 3.42; Comprehensive Assessment of At-Risk Mental States symptom severity 0.29, 95% confidence interval -4.35 to 4.94; or distress treatment effect 4.09, 95% confidence interval -3.52 to 11.70. Greater Comprehensive Assessment of At-Risk Mental States for psychosis scores reflect greater symptom severity. We found no evidence of significant differences at 9 or 24 months. Social recovery therapy was not estimated to be cost-effective. The key limitation was that missingness of data was consistently greater in the enhanced standard care-alone arm (9% primary outcome and 15% secondary outcome missingness of data) than in the social recovery therapy plus enhanced standard care arm (4% primary outcome and 9% secondary outcome missingness of data) at 15 months. CONCLUSIONS: We found no evidence for the clinical superiority or cost-effectiveness of social recovery therapy as an adjunct to enhanced standard care. Both arms made large improvements in primary and secondary outcomes. Enhanced standard care included a comprehensive combination of evidence-based pharmacological, psychotherapeutic and psychosocial interventions. Some results favoured enhanced standard care but the majority were not statistically significant. Future work should identify factors associated with the optimal delivery of the combinations of interventions that underpin better outcomes in this often-neglected clinical group. TRIAL REGISTRATION: Current Controlled Trials ISRCTN47998710. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment Vol. 25, No. 70. See the NIHR Journals Library website for further project information.

Young people with social disability and non-psychotic severe and complex mental health problems are an important group. Their problems are often long-standing and they often have difficulty doing 'structured activity', such as work, sports and leisure activities (e.g. going shopping or to the cinema). They often avoid such activities because of anxiety or low mood. Other barriers may include financial and practical issues, and stigma from activity providers. Non-participation in structured activity increases the risk that mental health problems will continue and prevent these young people from reaching meaningful goals. We tested whether or not social recovery therapy might help. This is a talking and activity therapy, in which young people (participants) work individually with a social recovery therapy therapist. Social recovery therapy aims to help participants identify what activities they would like to do, practise spending more time doing them, and work through barriers to maintaining increased activity. By improving structured activity, young people feel more hopeful and better able to manage their symptoms. However, social recovery therapy has never been evaluated properly using the best research methods. The best way to evaluate treatments like this is a randomised controlled trial in which participants are allocated by chance, like tossing a coin, to have the new therapy or not to have the therapy. Both groups are followed up for a period to see if the new therapy works. We tested social recovery therapy in this way. We also tested whether or not it was cost-effective. We recruited 270 16- to 25-year-old participants in Sussex, East Anglia and Manchester. Participants had non-psychotic severe and complex mental health problems (not psychosis) and were doing < 30 hours of structured activity per week at the start of the study. All participants had enhanced standard care. This involved standard NHS treatment plus a full assessment and feedback from the study team, and a best practice guide to local support services that encouraged the best provision of standard evidence-based interventions. Half of the participants were randomly allocated to have social recovery therapy in addition to enhanced standard care over 9 months. All participants were invited to assessments 9, 15 and 24 months later. Therapists recorded the tasks and activities undertaken with participants. We asked both participants and therapists what they thought of the trial and the social recovery therapy. We found no evidence that adding social recovery therapy improved outcomes. Participants in both arms made large and clinically worthwhile improvements in structured activity and mental health outcomes. If anything, there was some evidence that people allocated to enhanced standard care improved more than those allocated to social recovery therapy plus enhanced standard care. The differences were small, however, and could have occurred by chance.

Resident experience of abuse and harassment in emergency medicine: ten years later.

BACKGROUND: In 1995, a Society for Academic Emergency Medicine in-service survey reported high rates of verbal and physical abuse experienced by Emergency Medicine (EM) residents. We sought to determine the prevalence of abuse and harassment 10 years later to bring attention to these issues and determine if there has been a change in the prevalence of abuse over this time period. OBJECTIVES: To determine the prevalence of abuse and harassment in a sample of EM residencies. METHODS: We conducted a cross-section survey of EM residents from 10 residencies. EM residents were asked about their experience with verbal abuse, verbal threats, physical threats, physical attacks, sexual harassment, and racial harassment; and by whom. The primary outcome of the study was the prevalence of abuse and harassment as reported by EM residents. RESULTS: There were 196 of 380 residents (52%) who completed the survey. The prevalence of any type of abuse experienced was 91%; 86% of residents experienced verbal abuse, 65% verbal threats, 50% physical threats, 26% physical attacks, 23% sexual harassment, and 26% racial harassment. Women were more likely than men to encounter sexual harassment (37% [38/102] vs. 8% [7/92]; p < 0.001). Racial harassment was not limited to minorities (23% [16/60] for Caucasians vs. 26% [29/126] for non-Caucasians; p = 0.59). Senior residents were more likely to have encountered verbal and physical abuse. Only 12% of residents formally reported the abuse they experienced. CONCLUSION: Abuse and harassment during EM residency continues to be commonplace and is underreported.

Regulation of latent sensory hair cell precursors by glia in the zebrafish lateral line.

The lateral line is a placodally derived mechanosensory organ in anamniotes that detects the movement of water. In zebrafish embryos, a migrating primordium deposits seven to nine clusters of sensory hair cells, or neuromasts, at intervals along the trunk. Postembryonically, neuromasts continue to be added. We show that some secondary neuromasts arise from a pool of latent precursors that are deposited by the primordium between primary neuromasts. Interneuromast cells lie adjacent to the lateral line nerve and associated glia. These cells remain quiescent while they are juxtaposed with the glia; however, when they move away from the nerve they increase proliferation and form neuromasts. If glia are manually removed or genetically ablated by mutations in cls/sox10, hypersensitive (hps), or rowgain (rog), neuromasts precociously differentiate. Transplantation of wt glia into mutants rescues the appropriate temporal differentiation of interneuromast cells. Our studies reveal a role for glia in regulating sensory hair cell precursors.

A collaborative protocol on oxytocin administration: bringing nurses, midwives and physicians together.

Oxytocin is a high-alert drug for which safety precautions are crucial. Clear communication between nurses, physicians and midwives is vital when oxytocin is used. A collaborative process to updating an oxytocin administration protocol results in trust and respect among health care providers.

Zebrafish Foxd3 is required for development of a subset of neural crest derivatives.

foxd3 encodes a winged helix/forkhead class transcription factor expressed in the premigratory neural crest cells of many vertebrates. We have investigated the function of this gene in zebrafish neural crest by a loss of function approach using antisense morpholino oligonucleotides and immunostaining for Foxd3 protein. Knockdown of Foxd3 expression produces deficits in several differentiated neural crest derivatives, including jaw cartilage, peripheral neurons, and glia, and iridophore pigment cells. Other derivatives, such as melanophore and xanthophore pigment cells are not affected. Reduction in the expression of several lineage-specific markers becomes evident soon after the onset of neural crest migration, suggesting that Foxd3 knockdown affects these lineages at early stages in their development. In contrast, analysis of the expression of early neural crest markers indicates little effect on neural crest induction or initial emigration. Finally, cell transplantation suggests that with respect to dorsal root ganglia neurons the Foxd3 requirement is cell autonomous, although Foxd3 itself is not detectable in differentiated DRG neurons. These results suggest that in zebrafish Foxd3 may not be required for induction of neural crest identity but is necessary for the differentiation of a subset of neural crest cell fates, perhaps in precursors of particular neural crest lineages.