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.

The burden of geriatric traumatic brain injury on trauma systems: Analysis of 348,800 Medicare inpatient claims.

BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and disability in older adults. The aim of this study was to characterize the burden of TBI in older adults by describing demographics, care location, diagnoses, outcomes, and payments in this high-risk group. METHODS: Using 2016-2019 Centers for Medicare & Medicaid Services (CMS) Inpatient Standard Analytical Files (IPSAF), patients >65 years with TBI (>1 injury ICD-10 starting with "S06") were selected. Trauma center levels were linked to the IPSAF file via American Hospital Association Hospital Provider ID and fuzzy-string matching. Patient variables were compared across trauma center levels. RESULTS: Three hundred forty-eight thousand eight hundred inpatients (50.4% female; 87.1% white) from 2963 US hospitals were included. Level I/II trauma centers treated 66.9% of patients; non-trauma centers treated 21.5%. Overall inter-facility transfer rate was 19.2%; in Level I/II trauma centers transfers-in represented 23.3% of admissions. Significant TBI (Head AIS ≥3) was present in 70.0%. Most frequent diagnoses were subdural hemorrhage (56.6%) and subarachnoid hemorrhage (30.6%). Neurosurgical operations were performed in 10.9% of patients and operative rates were similar regardless of center level. Total unadjusted mortality for the sample was 13.9%, with a mortality of 8.1% for those who expired in-hospital, and an additional 5.8% for those discharged to hospice. Medicare payments totaled $4.91B, with the majority (73.4%) going to Level I/II trauma centers. CONCLUSIONS: This study fills a gap in TBI research by demonstrating that although the majority of older adult TBI patients in the United States receive care at Level I/II trauma centers, a substantial percentage are managed at other facilities, despite 1 in 10 requiring neurosurgical operation regardless of level of trauma center. This analysis provides preliminary data on the function of regionalized trauma care for older adult TBI care. Future studies assessing the efficacy of early care guidelines in this population are warranted.

The public health burden of geriatric trauma: Analysis of 2,688,008 hospitalizations from Centers for Medicare and Medicaid Services inpatient claims.

BACKGROUND: Geriatric trauma care (GTC) represents an increasing proportion of injury care, but associated public health research on outcomes and expenditures is limited. The purpose of this study was to describe GTC characteristics, location, diagnoses, and expenditures. METHODS: Patients at short-term nonfederal hospitals, 65 years or older, with ≥1 injury International Classification of Diseases, Tenth Revision, were selected from 2016 to 2019 Centers for Medicare and Medicaid Services Inpatient Standard Analytical Files. Trauma center levels were linked to Inpatient Standard Analytical Files data via American Hospital Association Hospital ID and fuzzy string matching. Demographics, care location, diagnoses, and expenditures were compared across groups. RESULTS: A total of 2,688,008 hospitalizations (62% female; 90% White; 71% falls; mean Injury Severity Score, 6.5) from 3,286 hospitals were included, comprising 8.5% of all Medicare inpatient hospitalizations. Level I centers encompassed 7.2% of the institutions (n = 236) but 21.2% of hospitalizations, while nontrauma centers represented 58.5% of institutions (n = 1,923) and 37.7% of hospitalizations. Compared with nontrauma centers, patients at Level I centers had higher Elixhauser scores (9.0 vs. 8.8) and Injury Severity Score (7.4 vs. 6.0; p < 0.0001). The most frequent primary diagnosis at all centers was hip/femur fracture (28.3%), followed by traumatic brain injury (10.1%). Expenditures totaled $32.9 billion for trauma-related hospitalizations, or 9.1% of total Medicare hospitalization expenditures and approximately 1.1% of the annual Medicare budget. The overall mortality rate was 3.5%. CONCLUSION: Geriatric trauma care accounts for 8.5% of all inpatient GTC and a similar percentage of expenditures, the most common injury being hip/femur fractures. The largest proportion of GTC occurs at nontrauma centers, emphasizing their vital role in trauma care. Public health prevention programs and GTC guidelines should be implemented by all hospitals, not just trauma centers. Further research is required to determine the optimal role of trauma systems in GTC, establish data-driven triage guidelines, and define the impact of trauma centers and nontrauma centers on GTC mortality. LEVEL OF EVIDENCE: Therapeutic/care management, Level III.

Costs and staffing resource requirements for adaptive clinical trials: quantitative and qualitative results from the Costing Adaptive Trials project.

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.

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. TRIAL REGISTRATION NUMBER: ISRCTN69371850.

Critical Role of Trauma and Emergency Surgery Physicians in Patient Satisfaction: An Analysis of Consumer Assessment of Healthcare Providers and Systems, Hospital Version Data from 186,779 Patients and 168 Hospitals in a National Healthcare System.

BACKGROUND: Trauma and emergency surgery patients are unique with regard to the sudden and unexpected nature of their hospitalization and this can adversely affect patient satisfaction, but, to our knowledge, no large study exists examining this issue. The purpose of this study was to investigate the major factors that affect satisfaction scores in trauma and emergency surgery patients. STUDY DESIGN: Consumer Assessment of Healthcare Providers and Systems, Hospital Version survey data from patients discharged in 2018-2019 from facilities in a national hospital system were obtained. Patients were categorized as trauma, emergency surgery, or direct admit surgery (elective surgery). Individual Consumer Assessment of Healthcare Providers and Systems, Hospital Version question scores were regressed on the score for "overall rating" to determine the primary, secondary, and tertiary satisfaction drivers. RESULTS: There were 186,779 patients from 168 hospitals included. As expected, the primary determinant of patient satisfaction was nursing communication for all groups. However, trauma and emergency surgery patients differed from elective surgery patients in that physician communication was the second most important factor in patient satisfaction, accounting for 12.0% (trauma) and 8.6% (emergency surgery) of the total variability in the overall rating beyond the variability explained by the primary driver. If physician communication received low ratings, it was unlikely that high scores in other metrics could compensate to bring the overall score above the 50th percentile. CONCLUSIONS: Acute care surgeons appear to play a uniquely important role in support of Consumer Assessment of Healthcare Providers and Systems, Hospital Version scores. These data emphasize the importance of physician communication, particularly when a prehospital physician-patient relationship does not exist. Future research should explore specific mechanisms by which physicians effectively communicate with patients.

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.

Many people who have arm weakness following a stroke feel that insufficient attention is paid by rehabilitation services to recovery of their arm. Unfortunately, it is currently unclear how best to provide rehabilitation to optimise recovery, but robot-assisted training and therapy programmes that focus on practising functional tasks are promising and require further evaluation. The Robot-Assisted Training for the Upper Limb after Stroke (RATULS) trial evaluated three approaches to rehabilitation for people with moderate or severe difficulty using their arm. These approaches were 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 based on repetitive practice of functional tasks and usual care. Robot-assisted training and the enhanced upper limb therapy programme were provided in an outpatient setting for 45 minutes per session, three times per week, for 12 weeks, in addition to usual care. The Massachusetts Institute of Technology-Manus robotic gym system was selected as it was felt to be the best available technology. The participant sits at a table, places their affected arm onto the Massachusetts Institute of Technology-Manus arm support and attempts to move their arm to play a game on the computer screen. Movements are assisted by the Massachusetts Institute of Technology-Manus if the patient cannot perform the movements themselves. The results of the RATULS trial show that robot-assisted training did not result in additional improvement in stroke survivors' arm use when compared with the enhanced upper limb therapy programme or usual care. Stroke survivors who received enhanced upper limb therapy experienced meaningful improvements in undertaking activities of daily living, when compared with those participants who received either robot-assisted training or usual care. Participants who received enhanced upper limb therapy also experienced benefits in their mobility, compared with usual care participants. Participants and therapists found both therapies acceptable, and described various benefits. A health economic analysis found that neither robot-assisted training nor the enhanced upper limb therapy programme was a cost-effective treatment for the NHS.

Cost-effectiveness of child caries management: a randomised controlled trial (FiCTION trial).

BACKGROUND: A three-arm parallel group, randomised controlled trial set in general dental practices in England, Scotland, and Wales was undertaken to evaluate three strategies to manage dental caries in primary teeth. Children, with at least one primary molar with caries into dentine, were randomised to receive Conventional with best practice prevention (C + P), Biological with best practice prevention (B + P), or best practice Prevention Alone (PA). METHODS: Data on costs were collected via case report forms completed by clinical staff at every visit. The co-primary outcomes were incidence of, and number of episodes of, dental pain and/or infection avoided. The three strategies were ranked in order of mean cost and a more costly strategy was compared with a less costly strategy in terms of incremental cost-effectiveness. Costs and outcomes were discounted at 3.5%. RESULTS: A total of 1144 children were randomised with data on 1058 children (C + P n = 352, B + P n = 352, PA n = 354) used in the analysis. On average, it costs £230 to manage dental caries in primary teeth over a period of up to 36 months. Managing children in PA was, on average, £19 (97.5% CI: -£18 to £55) less costly than managing those in B + P. In terms of effectiveness, on average, there were fewer incidences of, (- 0.06; 97.5% CI: - 0.14 to 0.02) and fewer episodes of dental pain and/or infection (- 0.14; 97.5% CI: - 0.29 to 0.71) in B + P compared to PA. C + P was unlikely to be considered cost-effective, as it was more costly and less effective than B + P. CONCLUSIONS: The mean cost of a child avoiding any dental pain and/or infection (incidence) was £330 and the mean cost per episode of dental pain and/or infection avoided was £130. At these thresholds B + P has the highest probability of being considered cost-effective. Over the willingness to pay thresholds considered, the probability of B + P being considered cost-effective never exceeded 75%. TRIAL REGISTRATION: The trial was prospectively registered with the ISRCTN (reference number ISRCTN77044005) on the 26th January 2009 and East of Scotland Research Ethics Committee provided ethical approved (REC reference: 12/ES/0047).

Best-practice prevention alone or with conventional or biological caries management for 3- to 7-year-olds: the FiCTION three-arm RCT.

BACKGROUND: Historically, lack of evidence for effective management of decay in primary teeth has caused uncertainty, but there is emerging evidence to support alternative strategies to conventional fillings, which are minimally invasive and prevention orientated. OBJECTIVES: The objectives were (1) to assess the clinical effectiveness and cost-effectiveness of three strategies for managing caries in primary teeth and (2) to assess quality of life, dental anxiety, the acceptability and experiences of children, parents and dental professionals, and caries development and/or progression. DESIGN: This was a multicentre, three-arm parallel-group, participant-randomised controlled trial. Allocation concealment was achieved by use of a centralised web-based randomisation facility hosted by Newcastle Clinical Trials Unit. SETTING: This trial was set in primary dental care in Scotland, England and Wales. PARTICIPANTS: Participants were NHS patients aged 3-7 years who were at a high risk of tooth decay and had at least one primary molar tooth with decay into dentine, but no pain/sepsis. INTERVENTIONS: Three interventions were employed: (1) conventional with best-practice prevention (local anaesthetic, carious tissue removal, filling placement), (2) biological with best-practice prevention (sealing-in decay, selective carious tissue removal and fissure sealants) and (3) best-practice prevention alone (dietary and toothbrushing advice, topical fluoride and fissure sealing of permanent teeth). MAIN OUTCOME MEASURES: The clinical effectiveness outcomes were the proportion of children with at least one episode (incidence) and the number of episodes, for each child, of dental pain or dental sepsis or both over the follow-up period. The cost-effectiveness outcomes were the cost per incidence of, and cost per episode of, dental pain and/or dental sepsis avoided over the follow-up period. RESULTS: A total of 72 dental practices were recruited and 1144 participants were randomised (conventional arm, n = 386; biological arm, n = 381; prevention alone arm, n = 377). Of these, 1058 were included in an intention-to-treat analysis (conventional arm, n = 352; biological arm, n = 352; prevention alone arm, n = 354). The median follow-up time was 33.8 months (interquartile range 23.8-36.7 months). The proportion of children with at least one episode of pain or sepsis or both was 42% (conventional arm), 40% (biological arm) and 45% (prevention alone arm). There was no evidence of a difference in incidence or episodes of pain/sepsis between arms. When comparing the biological arm with the conventional arm, the risk difference was -0.02 (97.5% confidence interval -0.10 to 0.06), which indicates, on average, a 2% reduced risk of dental pain and/or dental sepsis in the biological arm compared with the conventional arm. Comparing the prevention alone arm with the conventional arm, the risk difference was 0.04 (97.5% confidence interval -0.04 to 0.12), which indicates, on average, a 4% increased risk of dental pain and/or dental sepsis in the prevention alone arm compared with the conventional arm. Compared with the conventional arm, there was no evidence of a difference in episodes of pain/sepsis among children in the biological arm (incident rate ratio 0.95, 97.5% confidence interval 0.75 to 1.21, which indicates that there were slightly fewer episodes, on average, in the biological arm than the conventional arm) or in the prevention alone arm (incident rate ratio 1.18, 97.5% confidence interval 0.94 to 1.48, which indicates that there were slightly more episodes in the prevention alone arm than the conventional arm). Over the willingness-to-pay values considered, the probability of the biological treatment approach being considered cost-effective was approximately no higher than 60% to avoid an incidence of dental pain and/or dental sepsis and no higher than 70% to avoid an episode of pain/sepsis. CONCLUSIONS: There was no evidence of an overall difference between the three treatment approaches for experience of, or number of episodes of, dental pain or dental sepsis or both over the follow-up period. FUTURE WORK: Recommendations for future work include exploring barriers to the use of conventional techniques for carious lesion detection and diagnosis (e.g. radiographs) and developing and evaluating suitable techniques and strategies for use in young children in primary care. TRIAL REGISTRATION: Current Controlled Trials ISRCTN77044005. 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. 1. See the NIHR Journals Library website for further project information.

WHAT WAS THE QUESTION?: Tooth decay is common; it can lead to pain, days off school for children and days off work for parents and is a financial burden to the NHS. There is uncertainty about the best way of managing decay in young children. This trial aimed to find out whether or not there was a difference in the amount of pain and/or infection suffered by children having their decay treated with one of the following: fillings, having decay sealed in or using preventative treatment alone. Which method represented the best value was also explored. WHAT DID WE DO?: For young children with decay, the Filling Children's Teeth: Indicated Or Not? (FiCTION) trial compared the difference between fillings, sealing in the decay and using preventative treatment alone over 3 years in NHS dental practices in Scotland, England and Wales. We recruited 1144 children aged 3­7 years with one or more holes in their baby back teeth (molars), but without pain/infection, and placed them at random into one of three groups: (1) tooth numbing, removing decay and filling(s) with preventative treatment; (2) sealing in decay with fillings or caps and preventative treatment but no numbing; or (3) preventative treatment alone. WHAT DID WE FIND?: Recruitment was challenging but was achieved. There was no evidence of a difference in children's experience of pain or infection, quality of life or dental anxiety between groups. All three ways of treating decay were acceptable to children, parents and dental professionals. Sealing in with preventative treatment was most likely to be considered the best way of managing children's decay if we are willing to pay a minimum of £130 to avoid an episode of pain or infection. WHAT DOES THIS MEAN?: As there was no evidence of a difference between the three treatment groups in pain/infection experienced, treatment choice should continue to be based on shared decision-making between the child, parent and clinician to agree the best option for the individual child.

Robot assisted training for the upper limb after stroke (RATULS): a multicentre randomised controlled trial.

BACKGROUND: Loss of arm function is a common problem after stroke. Robot-assisted training might improve arm function and activities of daily living. We compared the clinical effectiveness of robot-assisted training using the MIT-Manus robotic gym with an enhanced upper limb therapy (EULT) programme based on repetitive functional task practice and with usual care. METHODS: RATULS was a pragmatic, multicentre, randomised controlled trial done at four UK centres. Stroke patients aged at least 18 years with moderate or severe upper limb functional limitation, between 1 week and 5 years after their first stroke, were randomly assigned (1:1:1) to receive robot-assisted training, EULT, or usual care. Robot-assisted training and EULT were provided for 45 min, three times per week for 12 weeks. Randomisation was internet-based using permuted block sequences. Treatment allocation was masked from outcome assessors but not from participants or therapists. The primary outcome was upper limb function success (defined using the Action Research Arm Test [ARAT]) at 3 months. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN69371850. FINDINGS: Between April 14, 2014, and April 30, 2018, 770 participants were enrolled and randomly assigned to either robot-assisted training (n=257), EULT (n=259), or usual care (n=254). The primary outcome of ARAT success was achieved by 103 (44%) of 232 patients in the robot-assisted training group, 118 (50%) of 234 in the EULT group, and 85 (42%) of 203 in the usual care group. Compared with usual care, robot-assisted training (adjusted odds ratio [aOR] 1·17 [98·3% CI 0·70-1·96]) and EULT (aOR 1·51 [0·90-2·51]) did not improve upper limb function; the effects of robot-assisted training did not differ from EULT (aOR 0·78 [0·48-1·27]). More participants in the robot-assisted training group (39 [15%] of 257) and EULT group (33 [13%] of 259) had serious adverse events than in the usual care group (20 [8%] of 254), but none were attributable to the intervention. INTERPRETATION: Robot-assisted training and EULT did not improve upper limb function after stroke compared with usual care for patients with moderate or severe upper limb functional limitation. These results do not support the use of robot-assisted training as provided in this trial in routine clinical practice. FUNDING: National Institute for Health Research Health Technology Assessment Programme.