Acceptability of Parental Financial Incentives and Quasi-Mandatory Interventions for Preschool Vaccinations: Triangulation of Findings from Three Linked Studies.

BACKGROUND: Childhood vaccinations are a core component of public health programmes globally. Recent measles outbreaks in the UK and USA have prompted debates about new ways to increase uptake of childhood vaccinations. Parental financial incentives and quasi-mandatory interventions (e.g. restricting entry to educational settings to fully vaccinated children) have been successfully used to increase uptake of childhood vaccinations in developing countries, but there is limited evidence of effectiveness in developed countries. Even if confirmed to be effective, widespread implementation of these interventions is dependent on acceptability to parents, professionals and other stakeholders. METHODS: We conducted a systematic review (n = 11 studies included), a qualitative study with parents (n = 91) and relevant professionals (n = 24), and an on-line survey with embedded discrete choice experiment with parents (n = 521) exploring acceptability of parental financial incentives and quasi-mandatory interventions for preschool vaccinations. Here we use Triangulation Protocol to synthesise findings from the three studies. RESULTS: There was a consistent recognition that incentives and quasi-mandatory interventions could be effective, particularly in more disadvantaged groups. Universal incentives were consistently preferred to targeted ones, but relative preferences for quasi-mandatory interventions and universal incentives varied between studies. The qualitative work revealed a consistent belief that financial incentives were not considered an appropriate motivation for vaccinating children. The costs of financial incentive interventions appeared particularly salient and there were consistent concerns in the qualitative work that incentives did not represent the best use of resources for promoting preschool vaccinations. Various suggestions for improving delivery of the current UK vaccination programme as an alternative to incentives and quasi-mandates were made. CONCLUSIONS: Parental financial incentives and quasi-mandatory interventions for increasing uptake of preschool vaccinations do not currently attract widespread enthusiastic support in the UK; but some potential benefits of these approaches are recognised.National Institute for Health Research (Grant ID: HTA 11/97/01)This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pone.015684

Nasal Airway Obstruction Study (NAIROS): a phase III, open-label, mixed-methods, multicentre randomised controlled trial of septoplasty versus medical management of a septal deviation with nasal obstruction

Background Septoplasty (surgery to straighten a deviation in the nasal septum) is a frequently performed operation worldwide, with approximately 250,000 performed annually in the US and 22,000 in the UK. Most septoplasties aim to improve diurnal and nocturnal nasal obstruction. The evidence base for septoplasty clinical effectiveness is hitherto very limited. Aims To establish, and inform guidance for, the best management strategy for individuals with nasal obstruction associated with a deviated septum. Methods/design A multicentre, mixed-methods, open label, randomised controlled trial of septoplasty versus medical management for adults with a deviated septum and a reduced nasal airway. Eligible patients will have septal deflection visible at nasendoscopy and a nasal symptom score ≥ 30 on the NOSE questionnaire. Surgical treatment comprises septoplasty with or without reduction of the inferior nasal turbinate on the anatomically wider side of the nose. Medical management comprises a nasal saline spray followed by a fluorinated steroid spray daily for six months. The recruitment target is 378 patients, recruited from up to 17 sites across Scotland, England and Wales. Randomisation will be on a 1:1 basis, stratified by gender and severity (NOSE score). Participants will be followed up for 12 months post randomisation. The primary outcome measure is the total SNOT-22 score at 6 months. Clinical and economic outcomes will be modelled against baseline severity (NOSE scale) to inform clinical decision-making. The study includes a recruitment enhancement process, and an economic evaluation. Discussion The NAIROS trial will evaluate the clinical effectiveness and cost-effectiveness of septoplasty versus medical management for adults with a deviated septum and symptoms of nasal blockage. Identifying those individuals most likely to benefit from surgery should enable more efficient and effective clinical decision-making, and avoid unnecessary operations where there is low likelihood of patient benefit

Economic evaluation of robot-assisted training versus an enhanced upper limb therapy programme or usual care for patients with moderate or severe upper limb functional limitation due to stroke: results from the RATULS randomised controlled trial

Objective To determine whether robot-assisted training is cost-effective compared with an enhanced upper limb therapy (EULT) programme or usual care. Design Economic evaluation within a randomised controlled trial. Setting Four National Health Service (NHS) centres in the UK: Queen’s Hospital, Barking, Havering and Redbridge University Hospitals NHS Trust; Northwick Park Hospital, London Northwest Healthcare NHS Trust; Queen Elizabeth University Hospital, NHS Greater Glasgow and Clyde; and North Tyneside General Hospital, Northumbria Healthcare NHS Foundation Trust. Participants 770 participants aged 18 years or older with moderate or severe upper limb functional limitation from first-ever stroke. Interventions Participants randomised to one of three programmes provided over a 12-week period: robot-assisted training plus usual care; the EULT programme plus usual care or usual care. Main economic outcome measures Mean healthcare resource use; costs to the NHS and personal social services in 2018 pounds; utility scores based on EQ-5D-5L responses and quality-adjusted life years (QALYs). Cost-effectiveness reported as incremental cost per QALY and cost-effectiveness acceptability curves. Results At 6 months, on average usual care was the least costly option (£3785) followed by EULT (£4451) with robot-assisted training being the most costly (£5387). The mean difference in total costs between the usual care and robot-assisted training groups (£1601) was statistically significant (p<0.001). Mean QALYs were highest for the EULT group (0.23) but no evidence of a difference (p=0.995) was observed between the robot-assisted training (0.21) and usual care groups (0.21). The incremental cost per QALY at 6 months for participants randomised to EULT compared with usual care was £74 100. Cost-effectiveness acceptability curves showed that robot-assisted training was unlikely to be cost-effective and that EULT had a 19% chance of being cost-effective at the £20 000 willingness to pay (WTP) threshold. Usual care was most likely to be cost-effective at all the WTP values considered in the analysis. Conclusions The cost-effectiveness analysis suggested that neither robot-assisted training nor EULT, as delivered in this trial, were likely to be cost-effective at any of the cost per QALY thresholds considered

The PRIDE database and related tools and resources in 2019: improving support for quantification data

The PRoteomics IDEntifications (PRIDE) database (https://www.ebi.ac.uk/pride/) is the world's largest data repository of mass spectrometry-based proteomics data, and is one of the founding members of the global ProteomeXchange (PX) consortium. In this manuscript, we summarize the developments in PRIDE resources and related tools since the previous update manuscript was published in Nucleic Acids Research in 2016. In the last 3years, public data sharing through PRIDE (as part of PX) has definitely become the norm in the field. In parallel, data re-use of public proteomics data has increased enormously, with multiple applications. We first describe the new architecture of PRIDE Archive, the archival component of PRIDE. PRIDE Archive and the related data submission framework have been further developed to support the increase in submitted data volumes and additional data types. A new scalable and fault tolerant storage backend, Application Programming Interface and web interface have been implemented, as a part of an ongoing process. Additionally, we emphasize the improved support for quantitative proteomics data through the mzTab format. At last, we outline key statistics on the current data contents and volume of downloads, and how PRIDE data are starting to be disseminated to added-value resources including Ensembl, UniProt and Expression Atlas

GaAs-based distributed feedback laser at 780 nm for 87

Summary form only given. The UK Quantum Technology Hub in Sensors and Metrology [1] has the aim of developing integrated, small and practical cold atom systems for a range of sensor and timing applications which includes rotation, magnetism, gravity and atomic clocks. The approach is similar to that pioneered by the chip scale atomic clock [2] where atoms held in microfabricated vacuum chambers have atomic transitions excited and probed by diodes lasers [3] and photodetectors. That system used coherent population trapping for the clock transitions whilst we are aiming to first produce lasers for cooling and trapping ions inside vacuum chambers before microwave pulses or controlled lasers are used to create superposition states, recombine them and measure the interference from the final state populations. For cooling 87Rb atoms, 780.24 nm lasers with linewidths below ~5 MHz are required whilst the lasers for controlling and measuring superposition states typically external cavity lasers have been used to achieve linewidths from 20 kHz [3] down to a few Hz [4]. Most single mode diode lasers aimed at laser cooling have used DBR gratings with regrowth [5] but this is challenging when using AlGaAs materials due to oxidation.Here we present single mode 780.24 nm DFB AlGaAs/GaAs lasers with output powers up to 50 mW and sidemode suppression ratios above 46 dB (Fig. 1(a)) using sidewall etched gratings (Fig. 1(b)) and no regrowth. The lasers demonstrate clear DFB performance allowing tuning through the required 780.24 nm without any mode hopping. Initial tests for short ridge devices indicate linewidths of ~10 MHz and initial lifetime tests have exceeded 200 hours. We will discuss methods being pursued to increasing the power and reducing the linewidth through longer ridges [5], coupled cavities and by integrating SOAs. Control of the population of electrons in hyperfine split states requires two laser outputs spaced by ~3.617 GHz. Fig 1(c) demonstrates the principle of two DFB lasers operated on the same waveguide where the present line spacing has been increased to 30 GHz to allow a clear measurement by our OSA. Careful control of the gratings and the current enable 3. 617 GHz to be achieved. We will present results comparing two coupled DFB lasers (Fig. 1(c)), direct modulation, external AOMs and integrated AOM approaches and discuss which are best suited for integrated cold atom systems

Dual bronchodilators in Bronchiectasis study (DIBS): protocol for a pragmatic, multicentre, placebo-controlled, three-arm, double-blinded, randomised controlled trial studying bronchodilators in preventing exacerbations of bronchiectasis

INTRODUCTION: Bronchiectasis is a long-term lung condition, with dilated bronchi, chronic inflammation, chronic infection and acute exacerbations. Recurrent exacerbations are associated with poorer clinical outcomes such as increased severity of lung disease, further exacerbations, hospitalisations, reduced quality of life and increased risk of death. Despite an increasing prevalence of bronchiectasis, there is a critical lack of high-quality studies into the disease and no treatments specifically approved for its treatment. This trial aims to establish whether inhaled dual bronchodilators (long acting beta agonist (LABA) and long acting muscarinic antagonist (LAMA)) taken as either a stand-alone therapy or in combination with inhaled corticosteroid (ICS) reduce the number of exacerbations of bronchiectasis requiring treatment with antibiotics during a 12 month treatment period. METHODS: This is a multicentre, pragmatic, double-blind, randomised controlled trial, incorporating an internal pilot and embedded economic evaluation. 600 adult patients (≥18 years) with CT confirmed bronchiectasis will be recruited and randomised to either inhaled dual therapy (LABA+LAMA), triple therapy (LABA+LAMA+ICS) or matched placebo, in a 2:2:1 ratio (respectively). The primary outcome is the number of protocol defined exacerbations requiring treatment with antibiotics during the 12 month treatment period. ETHICS AND DISSEMINATION: Favourable ethical opinion was received from the North East-Newcastle and North Tyneside 2 Research Ethics Committee (reference: 21/NE/0020). Results will be disseminated in peer-reviewed publications, at national and international conferences, in the NIHR Health Technology Assessments journal and to participants and the public (using lay language). TRIAL REGISTRATION NUMBER: ISRCTN15988757

Robot-assisted training compared with an enhanced upper limb therapy programme and with usual care for upper limb functional limitation after stroke: the RATULS three-group RCT

Background Loss of arm function is common after stroke. Robot-assisted training may improve arm outcomes. Objective The objectives were to determine the clinical effectiveness and cost-effectiveness of robot-assisted training, compared with an enhanced upper limb therapy programme and with usual care. Design This was a pragmatic, observer-blind, multicentre randomised controlled trial with embedded health economic and process evaluations. Setting The trial was set in four NHS trial centres. Participants Patients with moderate or severe upper limb functional limitation, between 1 week and 5 years following first stroke, were recruited. Interventions Robot-assisted training using the Massachusetts Institute of Technology-Manus robotic gym system (InMotion commercial version, Interactive Motion Technologies, Inc., Watertown, MA, USA), an enhanced upper limb therapy programme comprising repetitive functional task practice, and usual care. Main outcome measures The primary outcome was upper limb functional recovery ‘success’ (assessed using the Action Research Arm Test) at 3 months. Secondary outcomes at 3 and 6 months were the Action Research Arm Test results, upper limb impairment (measured using the Fugl-Meyer Assessment), activities of daily living (measured using the Barthel Activities of Daily Living Index), quality of life (measured using the Stroke Impact Scale), resource use costs and quality-adjusted life-years. Results A total of 770 participants were randomised (robot-assisted training, n = 257; enhanced upper limb therapy, n = 259; usual care, n = 254). Upper limb functional recovery ‘success’ was achieved in the robot-assisted training [103/232 (44%)], enhanced upper limb therapy [118/234 (50%)] and usual care groups [85/203 (42%)]. These differences were not statistically significant; the adjusted odds ratios were as follows: robot-assisted training versus usual care, 1.2 (98.33% confidence interval 0.7 to 2.0); enhanced upper limb therapy versus usual care, 1.5 (98.33% confidence interval 0.9 to 2.5); and robot-assisted training versus enhanced upper limb therapy, 0.8 (98.33% confidence interval 0.5 to 1.3). The robot-assisted training group had less upper limb impairment (as measured by the Fugl-Meyer Assessment motor subscale) than the usual care group at 3 and 6 months. The enhanced upper limb therapy group had less upper limb impairment (as measured by the Fugl-Meyer Assessment motor subscale), better mobility (as measured by the Stroke Impact Scale mobility domain) and better performance in activities of daily living (as measured by the Stroke Impact Scale activities of daily living domain) than the usual care group, at 3 months. The robot-assisted training group performed less well in activities of daily living (as measured by the Stroke Impact Scale activities of daily living domain) than the enhanced upper limb therapy group at 3 months. No other differences were clinically important and statistically significant. Participants found the robot-assisted training and the enhanced upper limb therapy group programmes acceptable. Neither intervention, as provided in this trial, was cost-effective at current National Institute for Health and Care Excellence willingness-to-pay thresholds for a quality-adjusted life-year. Conclusions Robot-assisted training did not improve upper limb function compared with usual care. Although robot-assisted training improved upper limb impairment, this did not translate into improvements in other outcomes. Enhanced upper limb therapy resulted in potentially important improvements on upper limb impairment, in performance of activities of daily living, and in mobility. Neither intervention was cost-effective. Future work Further research is needed to find ways to translate the improvements in upper limb impairment seen with robot-assisted training into improvements in upper limb function and activities of daily living. Innovations to make rehabilitation programmes more cost-effective are required. Limitations Pragmatic inclusion criteria led to the recruitment of some participants with little prospect of recovery. The attrition rate was higher in the usual care group than in the robot-assisted training or enhanced upper limb therapy groups, and differential attrition is a potential source of bias. Obtaining accurate information about the usual care that participants were receiving was a challenge. Trial registration Current Controlled Trials ISRCTN69371850. 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. 24, No. 54. See the NIHR Journals Library website for further project information

Evaluation of the enhanced upper limb therapy programme within the Robot-Assisted Training for the Upper Limb after Stroke trial: descriptive analysis of intervention fidelity, goal selection and goal achievement

Objective: To report the fidelity of the enhanced upper limb therapy programme within the Robot-Assisted Training for the Upper Limb after stroke (RATULS) randomized controlled trial, the types of goals selected and the proportion of goals achieved. Design: Descriptive analysis of data on fidelity, goal selection and achievement from an intervention group within a randomized controlled trial. Setting: Out-patient stroke rehabilitation within four UK NHS centres. Subjects: 259 participants with moderate-severe upper limb activity limitation (Action Research Arm Test 0–39) between one week and five years post first stroke. Intervention: The enhanced upper limb therapy programme aimed to provide 36 one-hour sessions, including 45 minutes of face-to-face therapy focusing on personal goals, over 12 weeks. Results: 7877/9324 (84%) sessions were attended; a median of 34 [IQR 29–36] per participant. A median of 127 [IQR 70–190] repetitions were achieved per participant per session attended. Based upon the Canadian Occupational Performance Measure, goal categories were: self-care 1449/2664 (54%); productivity 374/2664 (14%); leisure 180/2664 (7%) and ‘other’ 661/2664 (25%). For the 2051/2664 goals for which data were available, 1287 (51%) were achieved, ranging between 27% by participants more than 12 months post stroke with baseline Action Research Arm Test scores 0–7, and 88% by those less than three months after stroke with scores 8–19. Conclusions: Intervention fidelity was high. Goals relating to self-care were most commonly selected. The proportion of goals achieved varied, depending on time post stroke and baseline arm activity limitation