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This article examines the ongoing efforts of trade unions in Ireland to protect and improve the working conditions of personal care workers amid employment and social policy regimes associated with a liberal welfare state. Comparatively low public expenditure on care and the increasing marketisation of care services have undermined the provision of decent work. This article assesses two major union campaigns related to personal care workers over two decades, and reviews the key priorities that have emerged for unions during the COVID-19 pandemic. We consider whether the outcomes of these campaigns have been converted into enhanced rewards for workers and discuss the continuing challenges for union campaigning.

The promotion of practices supporting positive mental health at work is increasingly important on employers’ agendas. However, within the HRM literature there is a relative dearth of research on how employers can facilitate reintegration into the workplace or first-time employment for employees with mental health issues. Publicly funded supports are emerging as a strategy that can provide targeted supports to both workers and employers. This paper aims to investigate the effectiveness of this approach by undertaking triadic research with employers, healthcare professionals, and workers using the service in the Irish context. We make recommendations regarding the enhancement of opportunities currently available to those with a mental health difficulty to return to and remain in employment. The paper contributes to our understanding of the nature of supports required to successfully facilitate employing or re-integrating those with a mental health disability or history of mental health problems into the workplace.

Background We aimed to assess the cost effectiveness of intravitreal ranibizumab (Lucentis), aflibercept (Eylea) and bevacizumab (Avastin) for the treatment of macular oedema due to central retinal vein occlusion. Methods We calculated costs and quality-adjusted life-years from the UK National Health Service and Personal Social Services perspective. We performed a within-trial analysis using the efficacy, safety, resource use and health utility data from a randomised controlled trial (LEAVO) over 100 weeks. We built a discrete event simulation to model long-term outcomes. We estimated utilities using the Visual-Functioning Questionnaire-Utility Index, EQ-5D and EQ-5D with an additional vision question. We used standard UK costs sources for 2018/19 and a cost of £28 per bevacizumab injection. We discounted costs and quality-adjusted life-years at 3.5% annually. Results Bevacizumab was the least costly intervention followed by ranibizumab and aflibercept in both the within-trial analysis (bevacizumab: £6292, ranibizumab: £13,014, aflibercept: £14,328) and long-term model (bevacizumab: £18,353, ranibizumab: £30,226, aflibercept: £35,026). Although LEAVO did not demonstrate bevacizumab to be non-inferior for the visual acuity primary outcome, the three interventions generated similar quality-adjusted life-years in both analyses. Bevacizumab was always the most cost-effective intervention at a threshold of £30,000 per quality-adjusted life-year, even using the list price of £243 per injection. Conclusions Wider adoption of bevacizumab for the treatment of macular oedema due to central retinal vein occlusion could result in substantial savings to healthcare systems and deliver similar health-related quality of life. However, patients, funders and ophthalmologists should be fully aware that LEAVO could not demonstrate that bevacizumab is non-inferior to the licensed agents.

I - The Personal Life of the Worker The impact of technology on employees’ working lives is receiving increasing attention. Developments in technology influence how we work in a number of ways including how work tasks are undertaken (shaped by automation and digitization possibilities) how employers monitor, control and evaluate work and increasingly, when and where we work. While advancements in technology can have many positive benefits in relation to flexible working and can provide opport...

This article examines the extent to which occupations within a sector differ in their experiences of employer-led flexibility and in their responses through collective power. Three occupations are analysed in the Irish education sector – academics, school teachers and school secretaries. It might be expected that higher-level occupations would have greater sources of occupational power to resist employer-led flexibility. We find varying levels of employer-led flexibility through non-standard employment across and within occupations. We conclude that trade unions have achieved varying levels of success in negotiating regulations on casualisation, but that the effectiveness of union responses is likely to be dependent on the particular conditions which gave rise to casualisation amongst occupations. In terms of the propensity for each occupation to have standard or non-standard employment over a lifetime of employment, we conclude that school teachers can be categorised as an ‘insider’ occupation, that school secretaries have evolved to an ‘outsider’ occupation, while lecturing academics are most at risk of transitioning from an insider to an outsider occupation.

PurposeThe current study aims to examine stress mindset as a moderator of the relationship between the work–family interface – work–family conflict (WFC) and enrichment (WFE) – and two work outcomes: job satisfaction and turnover intentions.Design/methodology/approachTo examine these relationships, a cross-sectional online survey was conducted in Ireland (N = 314). Bootstrapping in SPSS was used to test the proposed hypotheses.FindingsIn addition to direct relationships between WFC/WFE and job satisfaction and turnover intentions, analyses showed that stress mindset is a moderator of the relationships between WFC and job satisfaction and turnover intentions, as well as of the relationship between WFE and job satisfaction, but not WFE and turnover intentions.Research limitations/implicationsProviding general support of the propositions of the conservation of resources theory, stress mindset was found to act as a personal resource affecting the relationships between WFC/WFE and most outcomes. The study findings indicate a need to further examine stress mindset in relation to employees' work and family interface.Practical implicationsIn line with other research, this study recommends organizational efforts to reduce WFC and increase WFE. Further, as stress mindsets can be altered, practitioners may consider implementing stress mindset training to encourage employees' view of stress as enhancing rather than debilitating to reduce the negative impact of stress on employees in the workplace.Social implicationsBeliefs about the enhancing aspects of stress may allow employees to more effectively navigate transitions between work and family domains and maximize beneficial aspects of participating in both work and family roles.Originality/valueThis is the first paper to investigate the role of stress mindset as a moderator of the associations between the work–family interface and employee work-related outcomes. The findings are relevant to work–family researchers, managers and human resource professionals.

Summary Background Occupational hand dermatitis poses a serious risk for nurses. Objectives To evaluate the clinical and cost‐effectiveness of a complex intervention in reducing the prevalence of hand dermatitis in nurses Methods This was a cluster randomized controlled trial conducted at 35 hospital trusts, health boards or universities in the UK. Participants were (i) first‐year student nurses with a history of atopic conditions or (ii) intensive care unit (ICU) nurses. Participants at intervention sites received access to a behavioural change programme plus moisturizing creams. Participants at control sites received usual care. The primary outcome was the change of prevalent dermatitis at follow‐up (adjusted for baseline dermatitis) in the intervention vs. the control group. Randomization was blinded to everyone bar the trials unit to ensure allocation concealment. The trial was registered on the ISRCTN registry: ISRCTN53303171. Results Fourteen sites were allocated to the intervention arm and 21 to the control arm. In total 2040 (69·5%) nurses consented to participate and were included in the intention‐to‐treat analysis. The baseline questionnaire was completed by 1727 (84·7%) participants. Overall, 789 (91·6%) ICU nurses and 938 (84·0%) student nurses returned completed questionnaires. Of these, 994 (57·6%) had photographs taken at baseline and follow‐up (12–15 months). When adjusted for baseline prevalence of dermatitis and follow‐up interval, the odds ratios (95% confidence intervals) for hand dermatitis at follow‐up in the intervention group relative to the controls were 0·72 (0·33–1·55) and 0·62 (0·35–1·10) for student and ICU nurses, respectively. No harms were reported. Conclusions There was insufficient evidence to conclude whether our intervention was effective in reducing hand dermatitis in our populations. Linked Comment: Brans. Br J Dermatol 2020; 183:411–412., What is already known about this topics? Nurses are at high risk of developing hand dermatitis.Educational interventions are only partially successful in preventing hand dermatitis in healthcare workers. What does this study add? The nurse participants in our study had a high level of positive beliefs about good hand care; however, this was not translated sufficiently into their behaviours even when they were provided with access to a behavioural change programme and given ready access to hand moisturizers.The behavioural change programme intervention did not have a significant effect on reducing hand dermatitis among at‐risk nurses. Linked Comment: Brans. Br J Dermatol 2020; 183:411–412. Plain language summary available online

Background Adaptive designs offer great promise in improving the efficiency and patient-benefit of clinical trials. An important barrier to further increased use is a lack of understanding about which additional resources are required to conduct a high-quality adaptive clinical trial, compared to a traditional fixed design. The Costing Adaptive Trials (CAT) project investigated which additional resources may be required to support adaptive trials. Methods We conducted a mock costing exercise amongst seven Clinical Trials Units (CTUs) in the UK. Five scenarios were developed, derived from funded clinical trials, where a non-adaptive version and an adaptive version were described. Each scenario represented a different type of adaptive design. CTU staff were asked to provide the costs and staff time they estimated would be needed to support the trial, categorised into specified areas (e.g. statistics, data management, trial management). This was calculated separately for the non-adaptive and adaptive version of the trial, allowing paired comparisons. Interviews with 10 CTU staff who had completed the costing exercise were conducted by qualitative researchers to explore reasons for similarities and differences. Results Estimated resources associated with conducting an adaptive trial were always (moderately) higher than for the non-adaptive equivalent. The median increase was between 2 and 4% for all scenarios, except for sample size re-estimation which was 26.5% (as the adaptive design could lead to a lengthened study period). The highest increase was for statistical staff, with lower increases for data management and trial management staff. The percentage increase in resources varied across different CTUs. The interviews identified possible explanations for differences, including (1) experience in adaptive trials, (2) the complexity of the non-adaptive and adaptive design, and (3) the extent of non-trial specific core infrastructure funding the CTU had. Conclusions This work sheds light on additional resources required to adequately support a high-quality adaptive trial. The percentage increase in costs for supporting an adaptive trial was generally modest and should not be a barrier to adaptive designs being cost-effective to use in practice. Informed by the results of this research, guidance for investigators and funders will be developed on appropriately resourcing adaptive trials.

Background Standalone thoracoscopic surgical ablation may be more effective than catheter ablation in patients with long-standing persistent atrial fibrillation. Objectives To determine whether or not surgical ablation is clinically superior to catheter ablation as the first-line treatment strategy in long-standing persistent atrial fibrillation. Design This was a prospective, multicentre, randomised control trial. Setting Four NHS tertiary centres in England. Participants Adults with long-standing persistent atrial fibrillation, who had European Heart Rhythm Association symptom scores > 2 and who were naive to previous catheter ablation or thoracic/cardiac surgery. Interventions Minimally invasive thoracoscopic surgical ablation and conventional catheter ablation (control intervention). Main outcome measures The primary outcome was freedom from atrial fibrillation/tachycardia ≥ 30 seconds after a single procedure without antiarrhythmic drugs (class 1C/3) at 1 year, excluding a 3-month blanking period. The secondary outcomes include the intervention-related major complication rate; clinical success (≥ 75% reduction in arrhythmia burden); and changes in symptoms, quality of life and cost-effectiveness. Methods Patients (n = 120) were randomised to surgical ablation (n = 60) or catheter ablation (n = 60). An implanted loop recorder provided continuous cardiac monitoring following ablation. Follow-up visits were at 3, 6, 9 and 12 months. Loop recorder data were reviewed monthly by a physiologist who was blinded to the randomisation outcome. Results The study treatment was received by 55 patients in the surgical ablation arm and 60 patients in the catheter ablation arm; five patients withdrew from surgical ablation before treatment. Data from randomised and treated patients were analysed as per intention to treat. Patients had a mean age of 62.3 (standard deviation 9.6) years, were predominantly male (74%), had a mean left atrial diameter of 44.6 mm (standard deviation 6 mm) and were in continuous atrial fibrillation for 22 months (range 16–31 months). At 12 months, 26% of patients in the surgical ablation arm (14/54) and 28% of patients in the catheter ablation arm (17/60) were free from atrial arrhythmias after a single procedure without antiarrhythmic drugs (odds ratio 1.13, 95% confidence interval 0.46 to 2.83; p = 0.84). An arrhythmia burden reduction of ≥ 75% was seen in 36 out of 54 (67%) patients in the surgical ablation arm, compared with 46 out of 60 (77%) patients in the catheter ablation arm (odds ratio 1.64, 95% confidence interval 0.67 to 4.08; p = 0.3). Procedure-related serious complications within 30 days of the intervention occurred in 15% (8/55) of patients in the surgical ablation arm (including one death) compared with 10% (6/60) of patients in the catheter ablation arm (p = 0.46). Surgical ablation was associated with significantly higher costs (£23,221 vs. £18,186; p = 0.02) and fewer quality-adjusted life-years than catheter ablation (0.76 vs. 0.83; p = 0.02). Limitations This study was conducted in four highly specialised cardiology centres that have substantial experience in both treatment modalities; therefore, the results may not be widely generalisable. The study was not powered to detect small differences in efficacy. Conclusions We found no evidence to suggest that standalone thoracoscopic surgical ablation outcomes were superior to catheter ablation outcomes in achieving freedom from atrial arrhythmia after a single procedure without antiarrhythmic drugs. Moreover, surgical ablation is associated with a longer hospital stay, smaller improvements in quality of life and higher health-care costs than catheter ablation (standard care therapy). Future work Evaluation of the impact of ablation treatments on sinus rhythm maintenance and quality of life with extended follow-up to 3 years. Model-based economic analysis to estimate long-term benefits, harms and costs of surgical and catheter ablation compared with antiarrhythmic drug therapy in long-standing persistent atrial fibrillation patients. Trial registration Current Controlled Trials ISRCTN18250790 and ClinicalTrials.gov NCT02755688. Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership. This study was supported by the UK Clinical Research Collaboration-registered King’s Clinical Trials Unit at King’s Health Partners, which is part funded by the NIHR Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and King’s College London and the NIHR Evaluation, Trials and Studies Coordinating Centre. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 8, No. 18. See the NIHR Journals Library website for further project information.

Introduction: Recruitment into trials in rare chronic pain conditions can be challenging, so such trials consequently are underpowered or fail. Methods: Drawing from our experience in conducting, to date, the largest academic trial in a rare chronic pain condition, complex regional pain syndrome, we have identified recruitment and retention strategies for successful trial conduct. Results: We present 13 strategies grouped across the categories of ‘setting the recruitment rate’, ‘networking’, ‘patient information’, ‘trial management’ and ‘patient retention’. Moreover, six recruitment risks are also discussed. A conservative recruitment estimate, based on audits of newly referred patients to the trial centres without taking into account availability of ‘old’ patients or recruitment from outside centres, and assuming a 55% patient refusal rate yielded accurate numbers. Conclusion: Appreciation of these identified recruitment challenges and opportunities may contribute to supporting prospective investigators when they design clinical trials for chronic pain patient population groups where it has been historically difficult to conduct high-quality and robust clinical trials.

Background Although strategies have been developed to minimise the risk of occupational hand dermatitis in nurses, their clinical effectiveness and cost-effectiveness remain unclear. Objectives The Skin Care Intervention in Nurses trial tested the hypothesis that a behaviour change package intervention, coupled with provision of hand moisturisers, could reduce the point prevalence of hand dermatitis when compared with standard care among nurses working in the NHS. The secondary aim was to assess the impact of the intervention on participants’ beliefs and behaviour regarding hand care, and the cost-effectiveness of the intervention in comparison with normal care. Design Cluster randomised controlled trial. Setting Thirty-five NHS hospital trusts/health boards/universities. Participants First-year student nurses with a history of atopic tendency, and full-time intensive care unit nurses. Intervention Sites were randomly allocated to be ‘intervention plus’ or ‘intervention light’. Participants at ‘intervention plus’ sites received access to a bespoke online behaviour change package intervention, coupled with personal supplies of moisturising cream (student nurses) and optimal availability of moisturising cream (intensive care unit nurses). Nurses at ‘intervention light’ sites received usual care, including a dermatitis prevention leaflet. Main outcome measure The difference between intervention plus and intervention light sites in the change of point prevalence of visible hand dermatitis was measured from images taken at baseline and at follow-up. Randomisation Fourteen sites were randomised to the intervention plus arm, and 21 sites were randomised to the intervention light arm. Blinding The participants, trial statistician, methodologist and the dermatologists interpreting the hand photographs were blinded to intervention assignment. Numbers analysed An intention-to-treat analysis was conducted on data from 845 student nurses and 1111 intensive care unit nurses. Results The intention-to-treat analysis showed no evidence that the risk of developing dermatitis was greater in the intervention light group than in the intervention plus group (student nurses: odds ratio 1.25, 95% confidence interval 0.59 to 2.69; intensive care unit nurses: odds ratio 1.41, 95% confidence interval 0.81 to 2.44). Both groups had high levels of baseline beliefs about the benefits of using hand moisturisers before, during and after work. The frequency of use of hand moisturisers before, during and after shifts was significantly higher in the intensive care unit nurses in the intervention plus arm at follow-up than in the comparator group nurses. For student nurses, the intervention plus group mean costs were £2 lower than those for the comparator and 0.00002 more quality-adjusted life-years were gained. For intensive care unit nurses, costs were £4 higher and 0.0016 fewer quality-adjusted life-years were gained. Harms No adverse events were reported. Limitations Only 44.5% of participants in the intervention plus arm accessed the behaviour change package. Conclusion The intervention did not result in a statistically significant decrease in the prevalence of hand dermatitis in the intervention plus group. Future work Participants had a high level of baseline beliefs about the importance of using hand moisturisers before, during and after work. Future research should focus on how workplace culture can be changed in order for that knowledge to be actioned. Trial registration Current Controlled Trials ISRCTN53303171. 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. 23, No. 58. See the NIHR Journals Library website for further project information.

Chronic rejection is the single biggest cause of premature kidney graft failure. HLA antibodies (Ab) are an established prognostic biomarker for premature graft failure so there is a need to test whether treatment decisions based on the presence of the biomarker can alter prognosis. The Optimised TacrolimuS and MMF for HLA Antibodies after Renal Transplantation (OuTSMART) trial combines two elements. Firstly, testing whether a routine screening programme for HLA Ab in all kidney transplant recipients is useful by comparing blinding versus unblinding of HLA Ab status. Secondly, for those found to be HLA Ab+, testing whether the introduction of a standard optimisation treatment protocol can reduce graft failure rates. OuTSMART is a prospective, open-labelled, randomised biomarker-based strategy (hybrid) trial, with two arms stratified by biomarker (HLA Ab) status. The primary outcome was amended from graft failure rates at 3 years to time to graft failure to increase power and require fewer participants to be recruited. Length of follow-up subsequently is variable, with all participants followed up for at least 43 months up to a maximum of 89 months. The primary outcome will be analysed using Cox regression adjusting for stratification factors. Analyses will be according to the intention-to-treat using all participants as randomised. Outcomes will be analysed comparing standard care versus biomarker-led care groups within the HLA Ab+ participants (including those who become HLA Ab+ through re-screening) as well as between HLA-Ab-unblinded and HLA-Ab-blinded groups using all participants. Changes to the primary outcome permit recruitment of fewer participants to achieve the same statistical power. Pre-stating the statistical analysis plan guards against changes to the analysis methods at the point of analysis that might otherwise introduce bias through knowledge of the data. Any deviations from the analysis plan will be justified in the final report. ISRCTN registry, ID: ISRCTN46157828 . Registered on 26 March 2013; EudraCT 2012–004308-36 . Registered on 10 December 2012.

Background: Opioid use disorder is a chronic, debilitating, and costly disorder that has increased in prevalence in many countries, with an associated sharp rise in mortality. Maintenance opioid agonist therapy is the first-line treatment, but many patients do not stop using illicit or non-prescribed drugs concomitantly. We aimed to test the efficacy and cost-effectiveness of a personalised psychosocial intervention implemented with a toolkit of behaviour-change techniques as an adjunct to opioid agonist therapy. Methods: We did a pragmatic, open-label, randomised controlled trial at a specialist UK National Health Service community addictions clinic in London, UK. Eligible patients were aged 18 years or older, met criteria for opioid or cocaine dependence, or both, in the past 12 months, and voluntarily sought continued oral maintenance opioid agonist therapy, which they had been prescribed for at least 6 weeks. All participants were treatment resistant (ie, had used illicit or non-prescribed opioids or cocaine on one or more days in the past 28 days at study screening, which was verified by positive urine drug screen). Participants were allocated (1:1) by a web-accessed randomisation sequence (stratified by opioid agonist medication, current cocaine use, and current rug use) to receive a personalised psychosocial intervention (comprising a flexible toolkit of psychological-change methods, including contingency management to reinforce abstinence, recovery activities, and clinic attendance) in addition to treatment as usual, or treatment as usual only (control group). The primary outcome was treatment response at 18 weeks, which was defined as abstinence from illicit and non-prescribed opioids and cocaine in the past 28 days, as measured with treatment outcomes profiles and urine drug screening. Taking a societal cost perspective, we did an evaluation of cost-effectiveness with a wide range of willingness-to-pay values for a unit improvement in the probability of treatment response. We also calculated quality-adjusted life-years (QALYs). Efficacy was analysed in a modified-intention-to-treat population, including all participants who were randomly allocated but excluding those who had previously completed the intervention. This trial is registered with ISRCTN, number ISRCTN69313751. The trial is completed. Findings: Between June 7, 2013, and Dec 21, 2015, we randomly allocated 136 participants to the psychosocial intervention group and 137 to the control group. The trial database was locked on April 19, 2017. Three patients (one in the psychosocial intervention group and two in the control group) who were re-randomised in error were excluded from the analysis. 22 (16%) of 135 patients in the psychosocial intervention group had a treatment response, compared with nine (7%) of 135 in the control group (adjusted log odds 1·20 [95% CI 0·01–2·37]; p=0·048). The psychosocial intervention had a higher probability of being cost-effective than treatment as usual. There was a probability range of 47–87% for willingness-to-pay thresholds of £0–1000 for a unit improvement in the probability of treatment response. QALYs were higher in the psychosocial intervention group than in the control group (mean difference 0·048 [95% CI 0·016–0·080]; p=0·004) in adjusted analyses, with 60% and 67% probabilities of cost-effectiveness at the UK National Institute for Health and Care Excellence's willingness-to-pay thresholds of £20 000 and £30 000 per QALY, respectively. The number of adverse events was similar between groups, and no severe adverse events in either group were judged to be treatment related. One participant in the control group was hospitalised with drug-injection-related sepsis and died. Interpretation: In maintenance opioid agonist therapy, an adjunctive personalised psychosocial intervention in addition to standard therapy was efficacious and cost-effective compared with standard therapy alone at helping treatment-resistant patients abstain from using illicit and non-prescribed opioids and cocaine. Funding: Indivior.

Background Hypoxia may contribute to the development and progression of diabetic macular oedema (DMO) and diabetic retinopathy. The photoreceptors are the most metabolically active cells in the retina and the rod photoreceptors consume the maximal amount of oxygen for dark adaptation. Therefore, a lightmask emitting 500- to 505-nm light and worn at night during sleep may prevent rod-related dark adaptation and, thereby, reduce the retinal oxygen consumption and improve or prevent progression of DMO and diabetic retinopathy as evidenced in small short-term studies. Objectives The clinical effectiveness and safety of using a lightmask to prevent dark adaptation as a treatment and preventative option was evaluated for DMO over 24 months. Design A Phase III, multicentre, prospective, single-masked, randomised controlled clinical trial that evaluated the clinical effectiveness and safety of a lightmask that prevents dark adaptation to treat and prevent non-central DMO versus standard care (i.e. non-lightmask arm) at 24 months. A subset of participants also enrolled for a mechanistic substudy that evaluated the role of hypoxia in DMO. Setting Fifteen NHS clinical sites in the UK. Participants Adults with non-centre-involving DMO. Intervention The participants were randomly assigned (1 : 1) to being offered a lightmask (Noctura 400 Sleep Masks, Polyphotonix Medical Ltd, Durham, UK) to wear at night during sleep to prevent dark adaptation or to the non-lightmask arm (standard care) for 24 months. The participants were evaluated every 4 months. Main outcome measure The primary outcome was defined as a change in retinal thickness at the zone of maximum thickness measured by spectral domain optical coherence tomography at 24 months in the study eye, analysed using a linear mixed-effects model that estimated adjusted treatment effects at both 12 and 24 months. Results A total of 308 participants were recruited between April 2014 and May 2015. A total of 155 participants in the lightmask arm and 153 in the control arm contributed to the intention-to-treat strategy. The lightmask arm did not show any difference in effect compared with the non-lightmask arm [adjusted mean difference between arms –0.65 µm, 95% confidence interval –6.90 to 5.59 µm; p = 0.84). The compliance of wearing the lightmask was suboptimal, as recorded electronically, from the returned lightmasks. There were no lightmask-related severe adverse events. The mechanistic study aimed at studying the effect of improving hypoxia by inhaling 100% oxygen or by offering lightmasks to wear during sleep at night over 12 months did not demonstrate any clinically beneficial effect on DMO. Conclusion The lightmask, as offered in this trial to prevent dark adaptation, did not show any treatment or preventative effect in participants with non-central oedema or diabetic retinopathy at 24 months. No effect was seen as early as 4 months when compliance was higher. Future work Future research is needed to evaluate the role of rod-induced hypoxia in the pathogenesis of DMO and diabetic retinopathy. Trial registration Current Controlled Trials ISRCTN85596558. Funding This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research partnership. The report will be published in full in Efficacy and Mechanism Evaluation; Vol. 6, No. 2. See the NIHR Journals Library website for further project information. The lightmasks were purchased at a discounted rate from Polyphotonix Medical Ltd.

Background Licensed ranibizumab (0.5 mg/0.05 ml Lucentis®; Novartis International AG, Basel, Switzerland) and aflibercept (2 mg/0.05 ml Eylea®; Bayer AG, Leverkusen, Germany) and unlicensed bevacizumab (1.25 mg/0.05 ml Avastin®; F. Hoffmann-La Roche AG, Basel, Switzerland) are used to treat macula oedema due to central retinal vein occlusion, but their relative clinical effectiveness, cost-effectiveness and impact on the UK NHS and Personal Social Services have never been directly compared over the typical disease treatment period. Objective The objective was to compare the clinical effectiveness and cost-effectiveness of three intravitreal antivascular endothelial growth factor agents for the management of macula oedema due to central retinal vein occlusion. Design This was a three-arm, double-masked, randomised controlled non-inferiority trial. Setting The trial was set in 44 UK NHS ophthalmology departments, between 2014 and 2018. Participants A total of 463 patients with visual impairment due to macula oedema secondary to central retinal vein occlusion were included in the trial. Interventions The participants were treated with repeated intravitreal injections of ranibizumab (n = 155), aflibercept (n = 154) or bevacizumab (n = 154). Main outcome measures The primary outcome was an increase in the best corrected visual acuity letter score from baseline to 100 weeks in the trial eye. The null hypothesis that aflibercept and bevacizumab are each inferior to ranibizumab was tested with a non-inferiority margin of –5 visual acuity letters over 100 weeks. Secondary outcomes included additional visual acuity, and imaging outcomes, Visual Function Questionnaire-25, EuroQol-5 Dimensions with and without a vision bolt-on, and drug side effects. Cost-effectiveness was estimated using treatment costs and Visual Function Questionnaire-Utility Index to measure quality-adjusted life-years. Results The adjusted mean changes at 100 weeks in the best corrected visual acuity letter scores were as follows – ranibizumab, 12.5 letters (standard deviation 21.1 letters); aflibercept, 15.1 letters (standard deviation 18.7 letters); and bevacizumab, 9.8 letters (standard deviation 21.4 letters). Aflibercept was non-inferior to ranibizumab in the intention-to-treat population (adjusted mean best corrected visual acuity difference 2.23 letters, 95% confidence interval –2.17 to 6.63 letters; p = 0.0006), but not superior. The study was unable to demonstrate that bevacizumab was non-inferior to ranibizumab in the intention-to-treat population (adjusted mean best corrected visual acuity difference –1.73 letters, 95% confidence interval –6.12 to 2.67 letters; p = 0.071). A post hoc analysis was unable to demonstrate that bevacizumab was non-inferior to aflibercept in the intention-to-treat population (adjusted mean best corrected visual acuity difference was –3.96 letters, 95% confidence interval –8.34 to 0.42 letters; p = 0.32). All per-protocol population results were the same. Fewer injections were required with aflibercept (10.0) than with ranibizumab (11.8) (difference in means –1.8, 95% confidence interval –2.9 to –0.8). A post hoc analysis showed that more bevacizumab than aflibercept injections were required (difference in means 1.6, 95% confidence interval 0.5 to 2.7). There were no new safety concerns. The model- and trial-based cost-effectiveness analyses estimated that bevacizumab was the most cost-effective treatment at a threshold of £20,000–30,000 per quality-adjusted life-year. Limitations The comparison of aflibercept and bevacizumab was a post hoc analysis. Conclusion The study showed aflibercept to be non-inferior to ranibizumab. However, the possibility that bevacizumab is worse than ranibizumab and aflibercept by 5 visual acuity letters cannot be ruled out. Bevacizumab is an economically attractive treatment alternative and would lead to substantial cost savings to the NHS and other health-care systems. However, uncertainty about its relative effectiveness should be discussed comprehensively with patients, their representatives and funders before treatment is considered. Future work To obtain extensive patient feedback and discuss with all stakeholders future bevacizumab NHS use. Trial registration Current Controlled Trials ISRCTN13623634. 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. 38. See the NIHR Journals Library website for further project information.

Objectiv eTo summarise current evidence for the utility of interval imaging in monitoring disease in adult brain tumours, and to develop a position for future evidence gathering while incorporating the application of data science and health economics.MethodsExperts in ‘interval imaging’ (imaging at pre-planned time-points to assess tumour status); data science; health economics, trial management of adult brain tumours, and patient representatives convened in London, UK. The current evidence on the use of interval imaging for monitoring brain tumours was reviewed. To improve the evidence that interval imaging has a role in disease management, we discussed specific themes of data science, health economics, statistical considerations, patient and carer perspectives, and multi-centre study design. Suggestions for future studies aimed at filling knowledge gaps were discussed.ResultsMeningioma and glioma were identified as priorities for interval imaging utility analysis. The “monitoring biomarkers” most commonly used in adult brain tumour patients were standard structural MRI features. Interval imaging was commonly scheduled to provide reported imaging prior to planned, regular clinic visits. There is limited evidence relating interval imaging in the absence of clinical deterioration to management change that alters morbidity, mortality, quality of life, or resource use. Progression-free survival is confounded as an outcome measure when using structural MRI in glioma. Uncertainty from imaging causes distress for some patients and their caregivers, while for others it provides an important indicator of disease activity. Any study design that changes imaging regimens should consider the potential for influencing current or planned therapeutic trials, ensure that opportunity costs are measured, and capture indirect benefits and added value.ConclusionEvidence for the value, and therefore utility, of regular interval imaging is currently lacking. Ongoing collaborative efforts will improve trial design and generate the evidence to optimise monitoring imaging biomarkers in standard of care brain tumour management.

Aims Long-standing persistent atrial fibrillation (LSPAF) is challenging to treat with suboptimal catheter ablation (CA) outcomes. Thoracoscopic surgical ablation (SA) has shown promising efficacy in atrial fibrillation (AF). This multicentre randomized controlled trial tested whether SA was superior to CA as the first interventional strategy in de novo LSPAF. Methods and results We randomized 120 LSPAF patients to SA or CA. All patients underwent predetermined lesion sets and implantable loop recorder insertion. Primary outcome was single procedure freedom from AF/atrial tachycardia (AT) ≥30 s without anti-arrhythmic drugs at 12 months. Secondary outcomes included clinical success (≥75% reduction in AF/AT burden); procedure-related serious adverse events; changes in patients’ symptoms and quality-of-life scores; and cost-effectiveness. At 12 months, freedom from AF/AT was recorded in 26% (14/54) of patients in SA vs. 28% (17/60) in the CA group [OR 1.128, 95% CI (0.46–2.83), P = 0.83]. Reduction in AF/AT burden ≥75% was recorded in 67% (36/54) vs. 77% (46/60) [OR 1.13, 95% CI (0.67–4.08), P = 0.3] in SA and CA groups, respectively. Procedure-related serious adverse events within 30 days of intervention were reported in 15% (8/55) of patients in SA vs. 10% (6/60) in CA, P = 0.46. One death was reported after SA. Improvements in AF symptoms were greater following CA. Over 12 months, SA was more expensive and provided fewer quality-adjusted life-years (QALYs) compared with CA (0.78 vs. 0.85, P = 0.02). Conclusion Single procedure thoracoscopic SA is not superior to CA in treating LSPAF. Catheter ablation provided greater improvements in symptoms and accrued significantly more QALYs during follow-up than SA. Clinical Trial Registration ISRCTN18250790 and ClinicalTrials.gov: NCT02755688, Graphical Abstract

peer-reviewed The full text of this article will not be available in ULIR until the embargo expires on the 27/06/2020 Increased levels of female labour market participation have impacted on the ability of families to provide care for elderly relatives in many industrialised societies. While work–family balance has received significant academic attention, less attention has focused specifically on individuals with eldercare responsibility, a cohort which accounts for a growing segment of the labour market internationally. Taking a qualitative research approach this paper uses work/family border theory to the constraints and facilitators to reconciling care and employment for employees working full-time in Ireland. The findings highlight the significant impact that eldercare provision has on employees with regard to day-to-day work commitments. We find that while general work–life balance policies exist within organisations, that the design and functionality of such policies are of limited value to elder caregivers. Furthermore, this paper highlights how the lack of formal HR policies around eldercare within organisations results in a reliance on supervisory discretion. We make some recommendations for organisational level strategies to address the needs of a growing number of caregivers. peer-reviewed

Background: Proliferative diabetic retinopathy is the most common cause of severe sight impairment in people with diabetes. Proliferative diabetic retinopathy has been managed by panretinal laser photocoagulation (PRP) for the past 40 years. We report the 1 year safety and efficacy of intravitreal aflibercept. Methods: In this phase 2b, single-blind, non-inferiority trial (CLARITY), adults (aged ≥18 years) with type 1 or 2 diabetes and previously untreated or post-laser treated active proliferative diabetic retinopathy were recruited from 22 UK ophthalmic centres. Patients were randomly assigned (1:1) to repeated intravitreal aflibercept (2 mg/0·05 mL at baseline, 4 weeks, and 8 weeks, and from week 12 patients were reviewed every 4 weeks and aflibercept injections were given as needed) or PRP standard care (single spot or mutlispot laser at baseline, fractionated fortnightly thereafter, and from week 12 patients were assessed every 8 weeks and treated with PRP as needed) for 52 weeks. Randomisation was by minimisation with a web-based computer generated system. Primary outcome assessors were masked optometrists. The treating ophthalmologists and participants were not masked. The primary outcome was defined as a change in best-corrected visual acuity at 52 weeks with a linear mixed-effect model that estimated adjusted treatment effects at both 12 weeks and 52 weeks, having excluded fluctuations in best corrected visual acuity owing to vitreous haemorrhage. This modified intention-to-treat analysis was reapplied to the per protocol participants. The non-inferiority margin was prespecified as −5 Early Treatment Diabetic Retinopathy Study letters. Safety was assessed in all participants. This trial is registered with ISRCTN registry, number 32207582. Findings: We recruited 232 participants (116 per group) between Aug 22, 2014 and Nov 30, 2015. 221 participants (112 in aflibercept group, 109 in PRP group) contributed to the modified intention-to-treat model, and 210 participants (104 in aflibercept group and 106 in PRP group) within per protocol. Aflibercept was non-inferior and superior to PRP in both the modified intention-to-treat population (mean best corrected visual acuity difference 3·9 letters [95% CI 2·3–5·6], p

Background Transverse myelitis (TM) is an immune-mediated disorder of the spinal cord that affects adults and children and that causes motor, sensory and autonomic dysfunction. There is a prolonged recovery phase, which may continue for many years. Neuromyelitis optica (NMO) is an uncommon relapsing inflammatory central nervous system condition in which TM can be the first presenting symptom. As TM and NMO affect many patients in the prime of their working life, the disorder can impose a significant demand on health resources. There are currently no robust controlled trials in children or adults to inform the optimal treatment of TM. However, treatment with intravenous immunoglobulin (IVIG) is being effectively used in the management of a range of neurological conditions. Although other interventions such as plasma exchange (PLEX) in addition to intravenous (IV) methylprednisolone therapy can be beneficial in TM, PLEX is costly and technically challenging to deliver in the acute setting. IVIG is more readily accessible and less costly. Objective To evaluate whether additional and early treatment with IVIG is of extra benefit in TM compared with standard therapy with IV steroids. Design A multicentre, single-blind, parallel-group randomised controlled trial of IVIG compared with standard therapy for the treatment of TM in adults and children. Participants Patients aged ≥ 1 year diagnosed with either acute first-onset TM or first presentation of NMO. Target recruitment was 170 participants (85 participants per arm). Interventions Participants were randomised 1 : 1 to treatment with IV methylprednisolone only or treatment with IV methylprednisolone plus 2 g/kg of IVIG in divided doses within 5 days of the first commencement of steroid therapy. Main outcome measures Primary outcome measure – American Spinal Injury Association (ASIA) Impairment Scale at 6 months post randomisation, with a good outcome defined by a two-grade change. Secondary and tertiary outcome measures – ASIA motor and sensory scales, Expanded Disability Status Scale, health outcome, quality of life, Client Service Receipt Inventory and International Spinal Cord Injury Pain, Bladder and Bowel Basic Data Sets. Results In total, 26 participants were screened and two were randomised into the study. With the limited sample size, treatment effect could not be determined. However, we identified barriers to accrual that included strict inclusion criteria, the short enrolment window, challenges associated with the use of the ASIA Impairment Scale as an outcome measure and estimation of the incidence of TM. Conclusions The study did not reach the end point and the effect of IVIG in TM/NMO could not be determined. Investigators should be aware of the potential challenges associated with carrying out a rare disease trial with a short enrolment window. The study question is one that still necessitates investigation. Preliminary work to ameliorate the effect of the barriers encountered in this study is vital. Trial registration EudraCT 2014-002335-34, ClinicalTrials.gov NCT02398994 and Current Controlled Trials ISRCTN12127581. Funding This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 31. See the NIHR Journals Library website for further project information. Funding was also received from Biotest AG, Germany (supply of IVIG) and the Transverse Myelitis Society (excess research cost to facilitate study initiation).

Background: The development of a nurse-led approach to managing epilepsy in adults with an intellectual disability offers the potential of improved outcomes and lower costs of care. We undertook a cluster randomised trial to assess the impact on costs and outcomes of the provision of intellectual disability nurses working to a designated epilepsy nurse competency framework. Here, we report the impact of the intervention on costs. Method: Across the UK, 8 sites randomly allocated to the intervention recruited 184 participants, 9 sites allocated to treatment as usual recruited 128 participants. Cost and outcome data were collected mainly by telephone interview at baseline and after six months. Total costs at six months were compared from the perspective of health & social services, and society, with adjustments for pre-specified participant and cluster characteristics at baseline including costs. Missing data was imputed using Multiple Imputation. Uncertainty was quantified by bootstrapping. Results: The intervention was associated with lower per participant costs from a health & social services perspective of -£357 (2014/15 GBP) (95% CI -£986, £294) and from a societal perspective of -£631 (95% CI -£1,473, £181). Results were not sensitive to the exclusion of accommodation costs. Conclusions: Our findings suggest that the competency framework is unlikely to increase the cost of caring for people with epilepsy and intellectual disability and may reduce costs., This paper presents independent research commissioned by the National Institute for Health Research (NIHR) under its Health Technology Assessment Programme (Grant 10/104/16 PI Dr H Ring). During the time that this research was carried out, H Ring also received support from the NIHR Collaboration for Leadership in Applied Health Research and Care (CLAHRC) East of England at Cambridgeshire and Peterborough NHS Foundation Trust.

‘Assumptions are made and most assumptions are wrong’ (Albert Einstein) Clinical trial conduct must be consistent with trial design, yet conducting the trial according to plan remains a major challenge. We discuss the importance of optimal co-applicant team formation in trial leadership, appropriate delegation of tasks and staff supervision arrangements. Finally, we discuss five standard documents which we believe require particular attention. With appropriate engagement by or with co-applicants during the preparation of these five standard documents, we believe many of the pitfalls trials commonly experience can be avoided. The risks inherent in failing to identify and address mistaken assumptions during the preparation of these documents are discussed and recommendations for best practice suggested.

Esophageal occlusion due to esophageal cancer is thankfully a rare occurrence. However, when it does present, it usually means there is advanced disease making surgical resection less effective. As such, there is a role for chemo and radiation therapies to treat the obstructing lesion as well as the systemic and locally advanced disease. In the case of metastatic disease, it can be used for palliation. For earlier or resectable disease, it can be used as neoadjuvant therapy to make a surgical cure more possible. The following chapter will discuss the indications, limitations, and timing for the use of chemo and radiation therapy for esophageal occlusions caused by malignancy.

Background People recovering from heroin addiction need better treatments than are currently offered. The chronic relapsing nature of drug dependence means that helping a patient to achieve abstinence is often difficult. Naltrexone blocks the effects of ingested heroin; however, evidence is conflicting regarding the best delivery method. Objectives The primary purpose of the trial was to evaluate the clinical effectiveness and cost-effectiveness of extended-release naltrexone versus standard oral naltrexone versus relapse prevention therapy without medication for opioid use disorder (OUD). Design This was a 3-year, definitive, three-centre, three-arm, parallel group, placebo-controlled, double-blind, double-dummy, randomised controlled trial. Setting Two specialist NHS outpatient addiction clinics: one in London and one in Birmingham. Participants Planned study sample – 300 adult patients with OUD who had completed detoxification. Interventions One iGen/Atral-Cipan Extended Release Naltrexone device (iGen/Atral-Cipan, Castanheira do Ribatejo, Portugal) (765 mg naltrexone or placebo) at day 0 of study week 1. Three weekly directly observed active or placebo oral naltrexone tablets (2 × 50 mg, Monday and Wednesday; 3 × 50 mg, Friday) at day 0 of study week 1 (for 4 weeks) and then an 8-week regimen of patient-administered dosing at the same dosing level. Main outcome measure The primary outcome measure was the proportion of heroin-negative urine drug screen (UDS) results at the end of the 12-week post-randomisation time point. Results Six patients were recruited and randomised to receive study interventions. Two patients had no positive UDS samples for heroin during the 12-week treatment period, one patient had only one positive UDS sample and the remaining patients had two, six and eight positive UDS results for heroin. All patients had at least one missed clinic visit (range 1–14). Conclusions Considerable problems were encountered with (1) the stipulated requirement of a validated ‘detoxified’ status prior to the initiation of the study naltrexone, (2) the requirement for a consent cooling-off period and (3) delays awaiting the surgical implant procedure. Major upheaval to the organisation and delivery of NHS community treatment services across England led to extremely poor levels of actual entry of patients into the trial. Research-vital clinical and procedural requirements were, therefore, more challenging to implement. The potential therapeutic value of the opioid antagonist naltrexone still needs clear investigation, including comparison of the established oral form with the new ultra-long-acting depot implant formulations (for which no licensed products exist in Europe). Despite the small number of study participants, some tentative conclusions can be reached, relevant to potential future work. The blinding of the active/placebo medications appeared to be good. Self-report was not sufficient to detect instances of heroin use. Self-report plus UDS information provided a fuller picture. Instances of lapsed heroin use were not necessarily followed by full relapse, and future work should consider the lapse–relapse relationship. The prison release setting also warrants special consideration. In future, investigators should consider seeking ethics approval for studies in which clinical procedures to accelerate the treatment process are permitted, even if outside orthodox clinical practice, if they address a clinical need at the time of challenge and clinical risk. In addition, it may be appropriate to seek exemption from the ordinary requirement of a cooling-off period after securing consent because it is often essential to initiate treatment promptly. Trial registration Current Controlled Trials ISRCTN95809946. 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. 23, No. 3. See the NIHR Journals Library website for further project information.

Trial design We present a study protocol for a multi-centre, randomised, double-blind, parallel-group, placebo-controlled trial that seeks to test the feasibility, acceptability and effectiveness of a 52-week period of treatment with the first-in-class co-stimulatory blocker abatacept for preventing or delaying the onset of inflammatory arthritis. Methods The study aimed to recruit 206 male or female subjects from the secondary care hospital setting across the UK and the Netherlands. Participants who were at least 18 years old, who reported inflammatory sounding joint pain (clinically suspicious arthralgia) and who were found to be positive for serum autoantibodies associated with rheumatoid arthritis (RA) were eligible for enrolment. All study subjects were randomly assigned to receive weekly injections of investigational medicinal product, either abatacept or placebo treatment over the course of a 52-week period. Participants were followed up for a further 52 weeks. The primary endpoint was defined as the time to development of at least three swollen joints or to the fulfilment of the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for RA using swollen but not tender joints, whichever endpoint was met first. In either case, swollen joints were confirmed by ultrasonography. Participants, care givers, and those assessing the outcomes were all blinded to group assignment. Clinical assessors and ultrasonographers were also blinded to each other’s assessments for the duration of the study. Conclusions There is limited experience of the design and implementation of trials for the prevention of inflammatory joint diseases. We discuss the rationale behind choice and duration of treatment and the challenges associated with defining the “at risk” state and offer pragmatic solutions in the protocol to enrolling subjects at risk of RA. Trial registration Current Controlled Trials, ID: ISRCTN46017566. Registered on 4 July 2014. Electronic supplementary material The online version of this article (10.1186/s13063-019-3403-7) contains supplementary material, which is available to authorized users.

This article investigates why workers submit to managerial bullying and, in doing so, we extend the growing research on managerial control and workplace bullying. We employ a labour process lens to explore the rationality of management both engaging in and perpetuating bullying. Labour process theory posits that employee submission to workplace bullying can be a valuable method of managerial control and this article examines this assertion. Based on the qualitative feedback in a large-scale survey of nurses in Ireland, we find that management reframed bullying complaints as deficiencies in the competency and citizenship of employees. Such reframing took place at various critical junctures such as when employees resisted extremely pressurized environments and when they resisted bullying behaviours. We find that such reframing succeeds in suppressing resistance and elicits compliance in achieving organisational objectives. We demonstrate how a pervasive bullying culture oriented towards expanding management control weakens an ethical climate conducive to collegiality and the exercise of voice, and strengthens a more instrumental climate. Whilst such a climate can have negative outcomes for individuals, it may achieve desired organisational outcomes for management.

This article examines union efforts to recruit and mobilise precarious workers in a hostile environment. Formidable obstacles confront organisers’ attempts to mobilise workers to engage in collective action at workplace level in the Irish hotel sector. After an initial grassroots organising campaign, the Services Industrial Professional and Technical Union (SIPTU) adopted a public campaign as an alternative strategy to secure improvements in pay and working conditions in the sector. Our findings indicate that the union’s inability to create a sense of collective identity among workers or establish strong support for union organisation at workplace level was due to a combination of external economic factors and challenges at this level. In the absence of such support, the impact of a public union campaign is less widely felt by employers. We evaluate the extent to which this type of campaign can substitute for weak grassroots mobilisation and provide a sustainable basis for union presence in the sector.

PurposeDrawing on human capital theory and the human capital resources framework, this study explores the knowledge, skills, abilities and other characteristics (KSAOs) required by the emerging role of human resource (HR) analysts. This study aims to systematically identify the key KSAOs and develop a competency model for HR Analysts amid the growing digitalization of work.Design/methodology/approachAdopting best practices for competency modeling set out by Campion et al. (2011), this study first analyzes 110 HR analyst job advertisements collected from five countries: Australia, Canada, Ireland, the United Kingdom and the USA. Second a thematic analysis of 12 in-depth semistructured interviews with HR analytics professionals from Canada and Ireland is then conducted to develop a novel competency model for HR Analysts.FindingsThis study adds to the developing and fast-growing field of HR analytics literature by offering evidence supporting a set of six distinct competencies required by HR Analysts including: consulting, technical knowledge, data fluency and data analysis, HR and business acumen, research and discovery and storytelling and communication.Practical implicationsThe research findings have several practical implications, specifically in recruitment and selection, HR development and HR system alignment.Originality/valueThis study contributes to the evolving HR analytics literature in two ways. First, the study links the role of HR Analysts to human capital theory and the human capital resource framework. Second, it offers a timely and empirically driven competency model for the emerging role of HR Analysts.

A 63-year-old woman with poorly controlled type 2 diabetes mellitus was admitted to the intensive care unit for increased respiratory support following large-volume fluid administration to treat diabetic ketoacidosis. The patient was intubated and diagnosed with mild acute respiratory distress

Coronary artery to coronary sinus fistula is a rare cardiac anomaly. We present the case of a male with recurrent abdominal pain found to have this condition. A 35-year-old male presented to the emergency room with complaint of abdominal pain. The patient denied a history of angina or angina

A 58-year-old man presented with a chief complaint of tongue indentations and discomfort. Otolaryngology treated him for oral thrush with counselling to avoid tongue biting. In addition, the patient reported dyspnoea described as a decrease in tolerance of his physical activities. Due to continued increase in tongue size and worsening dyspnoea, he underwent a tissue biopsy with findings consistent with amyloidosis. Further evaluation with a bone marrow biopsy revealed underlying multiple myeloma. Echocardiography revealed abnormal ventricular wall thickness, with a reduced left ventricular chamber size, dilated atria and Doppler findings with restrictive filling patterns indicative of cardiac amyloidosis. The patient was initiated on chemotherapy for his multiple myeloma and supportive therapy for his cardiac amyloidosis. Light-chain amyloidosis (AL) is a systemic disease characterised by irreversible deposition of amyloid in tissues throughout the body; when there is cardiac involvement, it can result in heart failure with a poor prognosis. Early diagnosis of cardiac amyloidosis can lead to prolonged survival.

Cancer is the cause of death for one in seven individuals worldwide. It is widely acknowledged that screening and early diagnosis are of vital importance for improving the likelihood of recovery. However, given the costly, time-consuming, and invasive nature of the many methods currently in use, patients often do not take advantage of the services available to them. Consequently, many researchers are exploring the possibility of developing fast, reliable, and non-invasive diagnostic tools that can be used directly or by local physicians at the point-of-care. Herein, we look at the use of established biomarkers in cancer therapy and investigate emerging biomarkers exhibiting future potential. The incorporation of these biomarkers into point-of-care devices could potentially reduce the strain currently experienced by screening programs in hospitals and healthcare systems. Results derived from point-of-care tests should be accurate, sensitive, and generated rapidly to assist in the selection of the best course of treatment for optimal patient care. Essentially, point-of-care diagnostics should enhance the well-being of patients and lead to a reduction in cancer-related deaths.

BACKGROUND: We aimed to assess 24-month outcomes of wearing an organic light-emitting sleep mask as an intervention to treat and prevent progression of non-central diabetic macular oedema.METHODS: CLEOPATRA was a phase 3, single-blind, parallel-group, randomised controlled trial undertaken at 15 ophthalmic centres in the UK. Adults with non-centre-involving diabetic macular oedema were randomly assigned (1:1) to wearing either a light mask during sleep (Noctura 400 Sleep Mask, PolyPhotonix Medical, Sedgefield, UK) or a sham (non-light) mask, for 24 months. Randomisation was by minimisation generated by a central web-based computer system. Outcome assessors were masked technicians and optometrists. The primary outcome was the change in maximum retinal thickness on optical coherence tomography (OCT) at 24 months, analysed using a linear mixed-effects model incorporating 4-monthly measurements and baseline adjustment. Analysis was done using the intention-to-treat principle in all randomised patients with OCT data. Safety was assessed in all patients. This trial is registered with Controlled-Trials.com, number ISRCTN85596558.FINDINGS: Between April 10, 2014, and June 15, 2015, 308 patients were randomly assigned to wearing the light mask (n=155) or a sham mask (n=153). 277 patients (144 assigned the light mask and 133 the sham mask) contributed to the mixed-effects model over time, including 246 patients with OCT data at 24 months. The change in maximum retinal thickness at 24 months did not differ between treatment groups (mean change -9·2 μm [SE 2·5] for the light mask vs -12·9 μm [SE 2·9] for the sham mask; adjusted mean difference -0·65 μm, 95% CI -6·90 to 5·59; p=0·84). Median compliance with wearing the light mask at 24 months was 19·5% (IQR 1·9-51·6). No serious adverse events were related to either mask. The most frequent adverse events related to the assigned treatment were discomfort on the eyes (14 with the light mask vs seven with the sham mask), painful, sticky, or watery eyes (14 vs six), and sleep disturbance (seven vs one).INTERPRETATION: The light mask as used in this study did not confer long-term therapeutic benefit on non-centre-involving diabetic macular oedema and the study does not support its use for this indication.FUNDING: The Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health Research partnership.

Background Panretinal photocoagulation (PRP) has been the standard of care for patients with proliferative diabetic retinopathy (PDR) for the last 40 years. It prevents severe visual loss in PDR but is also associated with adverse effects on visual functions. Objectives The clinical efficacy and mechanistic evaluation of aflibercept for proliferative diabetic retinopathy (CLARITY) trial evaluated the clinical efficacy, mechanisms and cost-effectiveness of intravitreal aflibercept (Eylea®, Regeneron, Tarrytown, NY, USA/Bayer Pharma AG, Berlin, Germany therapy for PDR. Design A multicentre, prospective, individually randomised, single-masked, active-controlled trial with concurrent economic evaluation that tested the non-inferiority of intravitreal aflibercept versus standard care PRP at 52 weeks. A subset of the participants enrolled in a mechanistic evaluation substudy. Setting 22 UK NHS clinical sites. Participants Patients aged at least 18 years having either treatment-naive PDR or active retinal neovascularisation (NV) despite prior PRP requiring treatment and best corrected visual acuity (BCVA) of 54 Early Treatment Diabetic Retinopathy Study (ETDRS) letters or better in the study eye were included. Eyes with evidence of macular oedema at baseline confirmed by central subfield thickness > 320 µm on spectral-domain optical coherence tomography were excluded. Intervention In the intervention arm, intravitreal aflibercept injections were given at baseline, 4 and 8 weeks and patients were subsequently reviewed every month and injected pro re nata based on the treatment response defined by degree of regression of retinal NV. In the comparator arm, PRP was completed in 2-weekly sessions and then supplemented if necessary at 8-weekly intervals. Main outcome measures The primary outcome was the mean change in BCVA at 52 weeks utilising a linear mixed-effects model incorporating data from both week 12 and week 52. Results A total of 232 participants (116 per arm) were recruited between August 2014 and November 2015. A total of 221 and 210 participants contributed to the intention-to-treat (ITT) model and per-protocol (PP) analysis, respectively. Economic evaluation was undertaken on 202 participants (101 per arm) with complete cost and outcome data. Aflibercept was non-inferior and superior to PRP in both the ITT population [mean BCVA difference 3.9 letters, 95% confidence interval (CI) 2.3 to 5.6 letters; p p Limitations This study is limited to 1 year of follow-up. Conclusions At an additional cost, the study shows that intravitreal aflibercept is an effective alternative treatment option for PDR in the first year. Future work Future research is needed to evaluate the long-term benefits of aflibercept in comparison with PRP and other anti-vascular endothelial growth factor agents for this condition. Trial registration Current Controlled Trials ISRCTN32207582. Funding This project was funded by the National Institute for Health Research (NIHR) Efficacy and Mechanistic Evaluation programme, a Medical Research Council and NIHR partnership. Aflibercept was supplied by Bayer Plc (Reading, UK). The study was sponsored by NIHR Moorfields Biomedical Research Centre and supported by the UK Clinical Research Network. The research was supported by the NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and University College London Institute of Ophthalmology, the NIHR Moorfields Clinical Research Facility and the UK Clinical Reasearch Collaboration-registered King’s Clinical Trials Unit at King’s Health Partners, which is partly funded by the NIHR Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and King’s College London.

Background Atrial fibrillation is the commonest arrhythmia which raises the risk of heart failure, thromboembolic stroke, morbidity and death. Pharmacological treatments of this condition are focused on heart rate control, rhythm control and reduction in risk of stroke. Selective ablation of cardiac tissues resulting in isolation of areas causing atrial fibrillation is another treatment strategy which can be delivered by two minimally invasive interventions: percutaneous catheter ablation and thoracoscopic surgical ablation. The main purpose of this trial is to compare the effectiveness and safety of these two interventions. Methods/design Catheter Ablation versus Thoracoscopic Surgical Ablation in Long Standing Persistent Atrial Fibrillation (CASA-AF) is a prospective, multi-centre, randomised controlled trial within three NHS tertiary cardiovascular centres specialising in treatment of atrial fibrillation. Eligible adults (n = 120) with symptomatic, long-standing, persistent atrial fibrillation will be randomly allocated to either catheter ablation or thoracoscopic ablation in a 1:1 ratio. Pre-determined lesion sets will be delivered in each treatment arm with confirmation of appropriate conduction block. All patients will have an implantable loop recorder (ILR) inserted subcutaneously immediately following ablation to enable continuous heart rhythm monitoring for at least 12 months. The devices will be programmed to detect episodes of atrial fibrillation and atrial tachycardia ≥ 30 s in duration. The patients will be followed for 12 months, completing appropriate clinical assessments and questionnaires every 3 months. The ILR data will be wirelessly transmitted daily and evaluated every month for the duration of the follow-up. The primary endpoint in the study is freedom from atrial fibrillation and atrial tachycardia at the end of the follow-up period. Discussion The CASA-AF Trial is a National Institute for Health Research-funded study that will provide first-class evidence on the comparative efficacy, safety and cost-effectiveness of thoracoscopic surgical ablation and conventional percutaneous catheter ablation for long-standing persistent atrial fibrillation. In addition, the results of the trial will provide information on the effects on patients’ quality of life. Trial registration ISRCTN Registry, ISRCTN18250790. Registered on 24 April 2015. Electronic supplementary material The online version of this article (10.1186/s13063-018-2487-9) contains supplementary material, which is available to authorized users.

BackgroundPeople with an intellectual (learning) disability (ID) and epilepsy have an increased seizure frequency, higher frequencies of multiple antiepileptic drug (AED) use and side effects, higher treatment costs, higher mortality rates and more behavioural problems than the rest of the population with epilepsy. The introduction of nurse-led care may lead to improvements in outcome for those with an ID and epilepsy; however, this has not been tested in a definitive clinical trial.ObjectiveTo determine whether or not ID nurses, using a competency framework developed to optimise nurse management of epilepsy in people with an ID, can cost-effectively improve clinical and quality-of-life outcomes in the management of epilepsy compared with treatment as usual.DesignCluster-randomised two-arm trial.SettingCommunity-based secondary care delivered by members of community ID teams.ParticipantsParticipants were adults aged 18–65 years with an ID and epilepsy under the care of a community ID team and had had at least one seizure in the 6 months before the trial.InterventionsThe experimental intervention was the Learning Disability Epilepsy Specialist Nurse Competency Framework. This provides guidelines describing a structure and goals to support the delivery of epilepsy care and management by ID-trained nurses.Main outcome measuresThe primary outcome was the seizure severity scale from the Epilepsy and Learning Disabilities Quality of Life questionnaire. Measures of mood, behaviour, AED side effects and carer strain were also collected. A cost–utility analysis was undertaken along with a qualitative examination of carers’ views of participants’ epilepsy management.ResultsIn total, 312 individuals were recruited into the study from 17 research clusters. Using an intention-to-treat analysis controlling for baseline individual-level and cluster-level variables there was no significant difference in seizure severity score between the two arms. Altogether, 238 complete cases were included in the non-imputed primary analysis. Analyses of the secondary outcomes revealed no significant differences between arms. A planned subgroup analysis identified a significant interaction between treatment arm and level of ID. There was a suggestion in those with mild to moderate ID that the competency framework may be associated with a small reduction in concerns over seizure severity (standard error 2.005, 95% confidence interval –0.554 to 7.307;p = 0.092). However, neither subgroup showed a significant intervention effect individually. Family members’ perceptions of nurses’ management depended on the professional status of the nurses, regardless of trial arm. Economic analysis suggested that the competency framework intervention was likely to be cost-effective, primarily because of a reduction in the costs of supporting participants compared with treatment as usual.LimitationsThe intervention could not be delivered blinded. Treatment as usual varied widely between the research sites.ConclusionsOverall, for adults with an ID and epilepsy, the framework conferred no clinical benefit compared with usual treatment. The economic analysis suggested that there may be a role for the framework in enhancing the cost-effectiveness of support for people with epilepsy and an ID. Future research could explore the specific value of the competency framework for those with a mild to moderate ID and the potential for greater long-term benefits arising from the continuing professional development element of the framework.Trial registrationCurrent Controlled Trials ISRCTN96895428.FundingThis trial was funded by the NIHR Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 22, No. 10. See the NIHR Journals Library website for further project information.

BACKGROUND: Opioid use disorder (OUD) is a debilitating, chronic and costly disorder, and is increasingly prevalent in many countries. Maintenance opioid agonist therapy (OAT) with oral methadone or oral buprenorphine is the first-line, empirically-supported treatment. However, many patients do not stop taking illicit drugs during OAT. We developed a personalised psychosocial intervention (PSI) to select behaviour change methods tailored to patient need and preference. The aim was to determine if this PSI adjunctive to on-going OAT can help treatment-resistant patients achieve abstinence. METHODS: This was a pragmatic, open-label, randomised controlled trial at a specialist NHS community addictions clinic. We recruited adults meeting Diagnostic and Statistical Manual of Mental Disorders IV criteria for opioid and/or cocaine dependence, enrolled in OAT for a median of 26 weeks (IQR 10-88), voluntarily seeking continued OAT, who were treatmentresistant. Treatment resistance was defined as using illicit or nonmedical opioids and/or cocaine on one or more days in the past 28 days at screening, verified by urine drug screen. Participants were allocated (1:1) by a Clinical Trials Unit managed, webaccessed, password-protected, randomisation sequence (stratified by OAT medication, cocaine use, and drug injecting) to receive continued OAT and standard case management (treatment-as-usual, TAU) or OAT TAU and a psychology assistant-delivered personalised PSI. Treatment was provided open-label. Outcome data were collected by independent research assistants. The primary outcome was treatment response at 18 weeks, defined as abstinence from illicit and non-prescribed opioids and cocaine in the past 28 days recorded by Treatment Outcomes Profile and negative urine drug screen. Taking a societal cost perspective, the evaluation of cost-effectiveness was done by taking a wide range of values of willingness-to-pay (WTP) for a unit improvement in the probability of treatment response, and EQ-5D-3L derived quality adjusted life years (QALYs). The planned analysis was intention-to-treat (ITT), including all those who were randomly allocated. This trial is registered with the ISRCTN registry, number ISRCTN69313751. FINDINGS: Between June 7, 2013 and December 21, 2015, we randomly allocated 136 patients (50%) to the PSI group and 137 patients (51%) to the TAU group. The trial database was locked for analysis on April 19, 2017. In error, we re-randomised three participants. These cases were excluded from all analysis. Due to this error, the analysis is classified as a modified ITT (mITT). All other randomised participants were included. PSI was superior to TAU. In the mITT analysis, there were 22 responders (16·3%) among the 135 participants in the PSI group, and 9 responders (6·7%) among the 135 participants in the TAU group (adjusted log odds 1·20; 95% CI 0·01 to 2·37; p-value=0·005). PSI had a higher probability of being cost-effective than TAU. There was a probability range of 47% to 87% for WTP thresholds of £0 to £1,000. QALYs were higher in the PSI group than the TAU (mean difference 0·048 [95% CI 0·016 to 0·080]; p-value=0·004), with a 60% and 67% probability of cost-effectiveness at the NICE willingness to pay thresholds of £20,000 and £30,000 per QALY, respectively. In the TAU group, one participant (1%) died (hospitalised with acute sepsis) and another (1%) had a serious adverse event (hospitalised with head injury). In the PSI group, one participant (1%) had a serious adverse event (hospitalised with panic attack). None of these events was judged to be trial-related. INTERPRETATION: We found a personalised PSI for OAT-resistant patients, delivered by psychology assistants, was effective and had a higher probability of being cost-effective compared to TAU. Treatment-resistant patients should be offered personalised PSI. Trial Registration Number: This trial is registered with the ISRCTN registry, number ISRCTN69313751. Funding: Unrestricted research grant to Action on Addiction from Indivior. Declaration of Interest: JM is supported by research grants from the Department of Health, Institute for Health Research (NIHR), and the NIHR Biomedical Research Centre for Mental Health at South London and Maudsley NHS Mental Health Foundation Trust (SLaM). He has part-time employment as Senior Academic Advisor for the Alcohol, Drugs, Tobacco and Justice Division, Health and Wellbeing Directorate, Public Health England. He declares an unrestricted research grant funding at IoPPN and SLaM to Action on Addiction from Indivior for the present study, and grant support from NIHR for a trial of oral and extended-release naltrexone. JM has received honoraria from PCM Scientific in relation to the Improving Outcomes in Treatment of Opioid Dependence conference (2015-2018). He holds no stocks in any company. JH was supported by a National Institute for Health Research (NIHR) doctoral fellowship. MK, GS and LM declare unrestricted research grant funding at IoPPN and SLaM to Action on Addiction from Indivior for the present study. Ethical Approval: Ethical approval for the study was granted by the UK National Health Service (London-Bromley Research Ethics Committee: 13/LO/0640). Details of the study protocol and PSI have been published.

Background Complex regional pain syndrome (CRPS) is a rare, severe post-traumatic pain condition affecting distal limbs. Patients who do not spontaneously improve in 12 months are classed as having ‘long-standing CRPS’ and often cannot be effectively treated, leading to a poor prognosis. CRPS is associated with functional autoantibodies. Two small trials, including a randomised controlled trial, have suggested that low-dose intravenous immunoglobulin (IVIg) may be an effective treatment for some patients. Objective We hypothesised that low-dose IVIg is effective for reducing pain in long-standing CRPS. Methods A randomised, double blinded placebo-controlled multicentre trial in seven UK pain management centres. Patients were eligible if they had moderate or severe long-standing CRPS that they had experienced for up to 5 years. Participants were randomly allocated to receive 0.5 g/kg IVIg, the active intervention, or visually indistinguishable 0.1% albumin in saline placebo. Randomisation was initiated by study sites via an independent online randomisation system and was 1 : 1 with varying block sizes, stratified by study centre. Participants, investigators and assessors were blinded to group assignment. The study drug/placebo was infused intravenously at the study centres on day 1 and day 23 after randomisation. The primary outcome was the 24-hour average pain intensity between day 6 and day 42, on an 11-point (0–10) numeric rating scale, compared between the groups. Outcomes were analysed using a mixed-effects regression model that used 37 measurements of pain intensity (the primary outcome) per participant. All patients who received an infusion and provided any outcome were included in the intention-to-treat analysis. Results A total of 111 patients were recruited and assigned between 27 August 2013 and 28 October 2015. Three patients were excluded because they had been inappropriately randomised, five patients were withdrawn from the primary analysis because they provided no outcomes and 103 patients were analysed for the primary outcome. The average pain score in the IVIg group was 0.27 units (95% confidence interval –0.24 to 0.80 units) higher than in the placebo group. Therefore, there is no significant evidence of a treatment effect at the 5% level and there was no significant difference between groups. Six serious adverse events but no suspected unexpected serious adverse reactions were reported during the blinded and open-label phase. Conclusion and future work Low-dose immunoglobulin was not effective in relieving pain in patients with moderate to severe CRPS of 1–5 years’ duration. Better drug treatments for long-standing CRPS are urgently required. Trial registration Current Controlled Trials ISRCTN42179756. Funding This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research partnership. Additional funding was obtained by the Pain Relief Foundation. Biotest UK Ltd provided the active study medication at no cost.

© 2017 American College of Physicians. Background: Two small trials suggest that low-dose intravenous immunoglobulin (IVIg) may improve the symptoms of complex regional pain syndrome (CRPS), a rare posttraumatic pain condition.Objective: To confirm the efficacy of low-dose IVIg compared with placebo in reducing pain during a 6-week period in adult patients who had CRPS from 1 to 5 years. Design: 1:1 parallel, randomized, placebo-controlled, multicenter trial for 6 weeks, with an optional 6-week open extension. Patients were randomly assigned to 1 of 2 study groups between 27 August 2013 and 28 October 2015; the last patient completed follow-up on 21 March 2016. Patients, providers, researchers, and outcome assessors were blinded to treatment assignment. (ISRCTN42179756) Setting: 7 secondary and tertiary care pain management centers in the United Kingdom. Participants: 111 patients with moderate or severe CRPS of 1 to 5 years' duration. Intervention: IVIg, 0.5 g/kg of body weight, or visually indistinguishable placebo of 0.1% albumin in saline on days 1 and 22 after randomization. Measurements: The primary outcome was 24-hour average pain intensity, measured daily between days 6 and 42, on an 11-point (0- to 10-point) rating scale. Secondary outcomes were pain interference and quality of life. Results: The primary analysis sample consisted of 108 eligible patients, 103 of whom had outcome data. Mean (average) pain scores were 6.9 points (SD, 1.5) for placebo and 7.2 points (SD, 1.3) for IVIg. The adjusted difference in means was 0.27 (95% CI, -0.25 to 0.80; P = 0.30), which excluded the prespecified, clinically important difference of -1.2. No statistically significant differences in secondary outcomes were found between the groups. In the open extension, 12 of the 67 patients (18%) who received 2 IVIg infusions had pain reduction of at least 2 points compared with their baseline score. Two patients in the blinded phase (1 in the placebo and 1 in the IVIg group) and 4 in the open IVIg phase had serious events. Limitations: Results do not apply to patients who have had CRPS for less than 1 year or more than 5 years and do not extend to full-dose treatment (for example, 2 g/kg). The study was inadequately powered to detect subgroup effects. Conclusion: Low-dose immunoglobulin treatment for 6 weeks was not effective in relieving pain in patients with moderate to severe CRPS of 1 to 5 years' duration.Primary Funding Source: Medical Research Council/National Institute for Health Research Efficacy and Mechanism Evaluation Program, Pain Relief Foundation, and Biotest United Kingdom.

Globally, there is an increasing demand for inexpensive and robust automated environmental monitoring platforms capable of performing analysis with prolonged deployment times. In the marine environment, the ultimate goal of these platforms is to remotely monitor water quality in real-time with a system capable of detecting numerous water quality parameters like nutrient species and the presence of pollutants/contaminants. These self-sustaining platforms allow for regular automated monitoring of selected parameters at remote locations. An autonomous platform is ideal when monitoring such precarious and problematic entities as harmful algal blooms. This research focuses on the challenges surrounding the sample pre-treatment requirements of an autonomous biosensor for the detection of algal toxins specifically Microcystin-LR, and describes the development of a one-step cell lysis procedure using mechanical force by copper beads in a lysing chamber. We report a sample extraction process from seawater samples that require no prior sample clean-up.

Bullying remains a pervasive problem in healthcare, and evidence suggests systems in place are not utilised due to perceptions of ineffectiveness and inequity. This study examines bystander responses to bullying and factors that influence decisions to intervene. We explore relationships between bystanders' perceptions of psychological safety across three levels (organisation, supervisor and colleague) and reactions to witnessing bullying. We suggest psychological safety would be positively associated with the decision to intervene. Findings indicate the most pervasive reaction to witnessing incidents of bullying is to discuss with colleagues, a low-involvement reaction. We find perceptions of supervisory and organisational safety/support are positively related to high-involvement decisions such as formal reporting of the incidents, highlighting the importance of support from those in power. However, perceptions of collegial support may lead to low-involvement responses, which risk reinforcing and underpinning dysfunctional organisational dynamics by providing informal social and emotional responses that may substitute more formal organisational responses to this persistent problem. This study highlights the importance of support from individuals in power if bystanders are to feel comfortable making high-involvement interventions.