Melina Dritsaki

Exercises to improve function of the rheumatoid hand (SARAH): a randomised controlled trial.

BACKGROUND Disease-modifying biological agents and other drug regimens have substantially improved control of disease activity and joint damage in people with rheumatoid arthritis of the hand. However, commensurate changes in function and quality of life are not always noted. Tailored hand exercises might provide additional improvements, but evidence is lacking. We estimated the effectiveness and cost-effectiveness of tailored hand exercises in addition to usual care during 12 months. METHODS In this pragmatic, multicentre, parallel-group trial, at 17 National Health Service sites across the UK we randomly assigned 490 adults with rheumatoid arthritis who had pain and dysfunction of the hands and had been on a stable drug regimen for at least 3 months, to either usual care or usual care plus a tailored strengthening and stretching hand exercise programme. Participants were randomly assigned with stratification by centre. Allocation was computer generated and unmasked to participants and therapists delivering treatment after randomisation. Outcome assessors and all investigators were masked to allocation. Physiotherapists or occupational therapists gave the treatments. The primary outcome was the Michigan Hand Outcomes Questionnaire overall hand function score at 12 months. The analysis was by intention to treat. We calculated cost per quality-adjusted life-year. This trial is registered as ISRCTN 89936343. FINDINGS Between Oct 5, 2009, and May 10, 2011, we screened 1606 people, of whom 490 were randomly assigned to usual care (n=244) or tailored exercises (n=246). 438 of 490 participants (89%) provided 12 month follow-up data. Improvements in overall hand function were 3·6 points (95% CI 1·5-5·7) in the usual care group and 7·9 points (6·0-9·9) in the exercise group (mean difference between groups 4·3, 95% CI 1·5-7·1; p=0·0028). Pain, drug regimens, and health-care resource use were stable for 12 months, with no difference between the groups. No serious adverse events associated with the treatment were recorded. The cost of tailored hand exercise was £156 per person; cost per quality-adjusted life-year was £9549 with the EQ-5D (£17,941 with imputation for missing data). INTERPRETATION We have shown that a tailored hand exercise programme is a worthwhile, low-cost intervention to provide as an adjunct to various drug regimens. Maximisation of the benefits of biological and DMARD regimens in terms of function, disability, and health-related quality of life should be an important treatment aim. FUNDING UK National Institute of Health Research Health Technology Assessment Programme (NIHR HTA), project number 07/32/05.

Strengthening and stretching for rheumatoid arthritis of the hand (SARAH). A randomised controlled trial and economic evaluation

BACKGROUND The effectiveness of exercise for improving hand and wrist function in people with rheumatoid arthritis (RA) is uncertain. OBJECTIVES The study aims were (1) to estimate the clinical effectiveness and cost-effectiveness of adding an optimised exercise programme for hands and upper limbs to standard care for patients with RA; and (2) to qualitatively describe the experience of participants in the trial with a particular emphasis on acceptability of the intervention, exercise behaviours and reasons for adherence/non-adherence. DESIGN A pragmatic, multicentred, individually randomised controlled trial with an embedded qualitative study. Outcome assessors were blind to group assignment and independent of treatment delivery. SETTING Seventeen NHS trusts in England comprising 21 rheumatology and therapy departments. PARTICIPANTS Adults with RA who had pain and dysfunction of the hands and/or wrists and had been on stable medication for at least 3 months. Patients were excluded if they were under 18 years old, had undergone upper limb surgery/fracture in the last 6 months, were on a waiting list for upper limb surgery or were pregnant. INTERVENTIONS Usual care or usual care plus an individualised exercise programme. Usual care consisted of joint protection education, general exercise advice and functional splinting if required. The exercise programme consisted of six sessions of strengthening and stretching exercises with a hand therapist, daily home exercises and strategies to maximise adherence. MAIN OUTCOME MEASURES The primary outcome was the Michigan Hand Outcome Questionnaire (MHQ) overall hand function subscale score at 12 months. Secondary outcome measures included the full MHQ, pain, health-related quality of life (Short Form questionnaire-12 items), impairment (grip strength, dexterity and range of motion) and self-efficacy. European Quality of Life-5 Dimensions, medication and health-care use were collected for the health economics evaluation. Follow-up was at 4 and 12 months post randomisation. Analysis was performed on an intention-to-treat basis. RESULTS We randomised 490 patients (244 to usual care, 246 to exercise programme). Compliance with the treatments was very good (93% of usual care participants and 75% of exercise programme participants completed treatment). Outcomes were obtained for 89% of participants at 12 months (222 for usual care, 216 for exercise programme). There was a statistically significant difference in favour of the exercise programme for the primary outcome at 4 and 12 months [mean difference 4.6 points, 95% confidence interval (CI) 2.2 to 7.0 points; and mean difference 4.4 points, 95% CI 1.6 to 7.1 points, respectively]. There were no significant differences in pain scores or adverse events. The estimated difference in mean quality-adjusted life-years (QALYs) accrued over 12 months was 0.01 greater (95% CI -0.03 to 0.05) in the exercise programme group. Imputed analysis produced incremental cost-effectiveness ratio estimates of £17,941 (0.59 probability of cost-effectiveness at willingness-to-pay threshold of £30,000 per QALY). The qualitative study found the exercise programme to be acceptable and highlighted the importance of the therapist in enabling patients to establish a routine and incorporate the exercises into their lives. CONCLUSIONS The results of the Strengthening And stretching for Rheumatoid Arthritis of the Hand trial suggest that the addition of an exercise programme for RA hands/wrists to usual care is clinically effective and cost-effective when compared with usual care alone. No adverse effects were associated with the exercise programme. The economic analysis suggests that the intervention is likely to be cost-effective. STUDY REGISTRATION Current Controlled Trials ISRCTN 89936343.

Economic costs associated with moderate and late preterm birth: a prospective population-based study.

We sought to determine the economic costs associated with moderate and late preterm birth.

Timely digital patient-clinician communication in specialist clinical services for young people: A mixed-methods study (the LYNC study)

Background Young people (aged 16-24 years) with long-term health conditions can disengage from health services, resulting in poor health outcomes, but clinicians in the UK National Health Service (NHS) are using digital communication to try to improve engagement. Evidence of effectiveness of this digital communication is equivocal. There are gaps in evidence as to how it might work, its cost, and ethical and safety issues. Objective Our objective was to understand how the use of digital communication between young people with long-term conditions and their NHS specialist clinicians changes engagement of the young people with their health care; and to identify costs and necessary safeguards. Methods We conducted mixed-methods case studies of 20 NHS specialist clinical teams from across England and Wales and their practice providing care for 13 different long-term physical or mental health conditions. We observed 79 clinical team members and interviewed 165 young people aged 16-24 years with a long-term health condition recruited via case study clinical teams, 173 clinical team members, and 16 information governance specialists from study NHS Trusts. We conducted a thematic analysis of how digital communication works, and analyzed ethics, safety and governance, and annual direct costs. Results Young people and their clinical teams variously used mobile phone calls, text messages, email, and voice over Internet protocol. Length of clinician use of digital communication varied from 1 to 13 years in 17 case studies, and was being considered in 3. Digital communication enables timely access for young people to the right clinician at the time when it can make a difference to how they manage their health condition. This is valued as an addition to traditional clinic appointments and can engage those otherwise disengaged, particularly at times of change for young people. It can enhance patient autonomy, empowerment and activation. It challenges the nature and boundaries of therapeutic relationships but can improve trust. The clinical teams studied had not themselves formally evaluated the impact of their intervention. Staff time is the main cost driver, but offsetting savings are likely elsewhere in the health service. Risks include increased dependence on clinicians, inadvertent disclosure of confidential information, and communication failures, which are mostly mitigated by young people and clinicians using common-sense approaches. Conclusions As NHS policy prompts more widespread use of digital communication to improve the health care experience, our findings suggest that benefit is most likely, and harms are mitigated, when digital communication is used with patients who already have a relationship of trust with the clinical team, and where there is identifiable need for patients to have flexible access, such as when transitioning between services, treatments, or lived context. Clinical teams need a proactive approach to ethics, governance, and patient safety.

Generic Preference-based Measures for Low Back Pain: Which of Them Should Be Used?

Study Design. Systematic review. Objective. This systematic review examines validity and responsiveness of three generic preference-based measures in patients with low back pain (LBP). Summary of Background Data. LBP is a very common incapacitating disease with a significant impact on health-related quality of life (HRQoL). Health state utility values can be derived from various preference-based HRQoL instruments, and among them the most widely ones are EuroQol 5 dimensions (EQ-5D), Short Form 6 Dimensions (SF-6D), and Health Utilities Index 3 (HUI III). The ability of these instruments to reflect HRQoL has been tested in various contexts, but never for LBP populations. Methods. A systematic search on electronic literature databases was undertaken to identify studies of patients with LBP where health state utility values were reported. Records were screened using a set of predefined eligibility criteria. Data on validity (correlations and known group methods) and responsiveness (effect sizes, standardized response means, tests of statistical significance) of instruments were extracted using a customized extraction template, and assessed using predefined criteria. Results. There were substantial variations in the 37 included papers identified in relation to study design and outcome measures used. EQ-5D demonstrated good convergent validity, as it was able to distinguish between known groups. EQ-5D was also able to capture changes of health states as results of different interventions. Evidence for SF-6D and HUI III was limited to allow an appropriate evaluation. Conclusion. EQ-5D performs well in LBP population and its scores seem to be suitable for economic evaluation of LBP interventions. However, the paucity of information on the other instruments makes it impossible to determine its relative validity and responsiveness compared with them. Level of Evidence: 2

An economic evaluation of a self-management programme of activity, coping and education for patients with chronic obstructive pulmonary disease

The aim was to undertake a cost-utility analysis of a self-management programme of activity, coping and education (SPACE) for chronic obstructive pulmonary disease (COPD). The analysis was conducted alongside a six-month randomized controlled trial in 30 primary care settings. The economic analysis used data from 184 patients with confirmed diagnosis of COPD, forced expiratory volume in one second/forced vital capacity ratio <0.7 and with grade 2–5 on the Medical Research Council dyspnoea scale. Participants received either a self-management programme consisting of an education manual (SPACE for COPD) and consultation or usual care. Six-month costs were estimated from the National Health Service and Personal Social Services perspective and quality-adjusted life years (QALYs) were calculated based on patient responses at baseline and six months. The mean difference in costs between usual care and SPACE FOR COPD programme was −£27.18 (95% confidence interval (CI); −£122.59 to £68.25) while mean difference in QALYs was −0.10 (95% CI; −0.17 to −0.02). The results suggest that the intervention is more costly and more effective than usual care. The probability of the intervention being cost-effective was 97% at a threshold of £20,000/QALY gained. We conclude that the SPACE FOR COPD programme is cost-effective compared to usual care.

Study protocol: A multi-centre, double blind, randomised, placebo-controlled, parallel group, phase II trial (RIDD) to determine the efficacy of intra-nodular injection of anti-TNF to control disease progression in early Dupuytren's disease, with an embedded dose response study.

Dupuytrens disease is a common fibrotic condition of the hand affecting 4% of the population and causes the fingers to curl irreversibly into the palm. It has a strong familial tendency, there is no approved treatment for early stage disease, and patients with established digital contractures are most commonly treated by surgery. This is associated with prolonged recovery, and less invasive techniques have high recurrence rates.The myofibroblasts, the cells responsible for the excessive matrix deposition and contraction, are aggregated in nodules. Using excised diseased and control human tissue, we found that immune cells interspersed amongst the myofibroblasts secrete cytokines. Of these, only tumour necrosis factor (TNF) promoted the development of myofibroblasts. The clinically approved anti-TNF agents led to inhibition of the myofibroblast phenotype in vitro. This clinical trial is designed to assess the efficacy of the anti-TNF agent adalimumab on participants with early disease. The first part is a dose-ranging study where nodules of participants already scheduled for surgery will be injected with either placebo (saline) or varying doses of adalimumab. The excised tissue will then be analysed for markers of myofibroblast activity.The second part of the study will recruit participants with early stage disease. They will be randomised 1: 1 to receive either adalimumab or placebo at 3 month intervals over 1 year and will then be followed for a further 6 months. Outcome measures will include nodule hardness, size and disease progression. The trial will also determine the cost-effectiveness of adalimumb treatment for this group of participants.

Labour induction near term for women aged 35 or over: an economic evaluation

Induction of labour at 39 weeks for nulliparous women aged 35 years and over may prevent stillbirths and does not increase caesarean births, so it may be popular. But the overall costs and benefits of such a policy have not been compared.

Intramedullary nail fixation versus locking plate fixation for adults with a fracture of the distal tibia: the UK FixDT RCT.

BACKGROUND The best treatment for fractures of the distal tibia remains controversial. Most of these fractures require surgical fixation, but the outcomes are unpredictable and complications are common. OBJECTIVES To assess disability, quality of life, complications and resource use in patients treated with intramedullary (IM) nail fixation versus locking plate fixation in the 12 months following a fracture of the distal tibia. DESIGN This was a multicentre randomised trial. SETTING The trial was conducted in 28 UK acute trauma centres from April 2013 to final follow-up in February 2017. PARTICIPANTS In total, 321 adult patients were recruited. Participants were excluded if they had open fractures, fractures involving the ankle joint, contraindication to nailing or inability to complete questionnaires. INTERVENTIONS IM nail fixation (n = 161), in which a metal rod is inserted into the hollow centre of the tibia, versus locking plate fixation (n = 160), in which a plate is attached to the surface of the tibia with fixed-angle screws. MAIN OUTCOME MEASURES The primary outcome measure was the Disability Rating Index (DRI) score, which ranges from 0 points (no disability) to 100 points (complete disability), at 6 months with a minimum clinically important difference of 8 points. The DRI score was also collected at 3 and 12 months. The secondary outcomes were the Olerud-Molander Ankle Score (OMAS), quality of life as measured using EuroQol-5 Dimensions (EQ-5D), complications such as infection, and further surgery. Resource use was collected to inform the health economic evaluation. RESULTS Participants had a mean age of 45 years (standard deviation 16.2 years), were predominantly male (61%, 197/321) and had experienced traumatic injury after a fall (69%, 223/321). There was no statistically significant difference in DRI score at 6 months [IM nail fixation group, mean 29.8 points, 95% confidence interval (CI) 26.1 to 33.7 points; locking plate group, mean 33.8 points, 95% CI 29.7 to 37.9 points; adjusted difference, 4.0 points, 95% CI -1.0 to 9.0 points; p = 0.11]. There was a statistically significant difference in DRI score at 3 months in favour of IM nail fixation (IM nail fixation group, mean 44.2 points, 95% CI 40.8 to 47.6 points; locking plate group, mean 52.6 points, 95% CI 49.3 to 55.9 points; adjusted difference 8.8 points, 95% CI 4.3 to 13.2 points; p < 0.001), but not at 12 months (IM nail fixation group, mean 23.1 points, 95% CI 18.9 to 27.2 points; locking plate group, 24.0 points, 95% CI 19.7 to 28.3 points; adjusted difference 1.9 points, 95% CI -3.2 to 6.9 points; p = 0.47). Secondary outcomes showed the same pattern, including a statistically significant difference in mean OMAS and EQ-5D scores at 3 and 6 months in favour of IM nail fixation. There were no statistically significant differences in complications, including the number of postoperative infections (13% in the locking plate group and 9% in the IM nail fixation group). Further surgery was more common in the locking plate group (12% in locking plate group and 8% in IM nail fixation group at 12 months). The economic evaluation showed that IM nail fixation provided a slightly higher quality of life in the 12 months after injury and at lower cost and, therefore, it was cost-effective compared with locking plate fixation. The probability of cost-effectiveness for IM nail fixation exceeded 90%, regardless of the value of the cost-effectiveness threshold. LIMITATIONS As wound dressings after surgery are clearly visible, it was not possible to blind the patients to their treatment allocation. This evidence does not apply to intra-articular (pilon) fractures of the distal tibia. CONCLUSIONS Among adults with an acute fracture of the distal tibia who were randomised to IM nail fixation or locking plate fixation, there were similar disability ratings at 6 months. However, recovery across all outcomes was faster in the IM nail fixation group and costs were lower. FUTURE WORK The potential benefit of IM nail fixation in several other fractures requires investigation. Research is also required into the role of adjuvant treatment and different rehabilitation strategies to accelerate recovery following a fracture of the tibia and other long-bone fractures in the lower limb. The patients in this trial will remain in longer-term follow-up. TRIAL REGISTRATION Current Controlled Trials ISRCTN99771224 and UKCRN 13761. 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. 22, No. 25. See the NIHR Journals Library website for further project information.

Methodological Issues Surrounding the Use of Baseline Health-Related Quality of Life Data to Inform Trial-Based Economic Evaluations of Interventions Within Emergency and Critical Care Settings: A Systematic Literature Review

BackgroundTrial-based cost-utility analyses require health-related quality of life data that generate utility values in order to express health outcomes in terms of quality-adjusted life years (QALYs). Assessments of baseline health-related quality of life are problematic where trial participants are incapacitated or critically ill at the time of randomisation. This review aims to identify and critique methods for handling non-availability of baseline health-related quality of life data in trial-based cost-utility analyses within emergency and critical illness settings.MethodsA systematic literature review was conducted, following PRISMA guidelines, to identify trial-based cost-utility analyses of interventions within emergency and critical care settings. Databases searched included the National Institute for Health Research (NIHR) Journals Library (1991–July 2016), Cochrane Library (all years); National Health Service (NHS) Economic Evaluation Database (all years) and Ovid MEDLINE/Embase (without time restriction). Strategies employed to handle non-availability of baseline health-related quality of life data in final QALY estimations were identified and critiqued.ResultsA total of 4224 published reports were screened, 19 of which met the study inclusion criteria (mean trial size 1670): 14 (74 %) from the UK, four (21%) from other European countries and one (5%) from India. Twelve studies (63%) were based in emergency departments and seven (37%) in intensive care units. Only one study was able to elicit patient-reported health-related quality of life at baseline. To overcome the lack of baseline data when estimating QALYs, eight studies (42%) assigned a fixed utility weight corresponding to either death, an unconscious health state or a country-specific norm to patients at baseline, four (21%) ignored baseline utilities, three (16%) applied values from another study, one (5%) generated utility values via retrospective recall and one (5%) elicited utilities from experts. A preliminary exploration of these methods shows that incremental QALY estimation is unlikely to be biased if balanced trial allocation is achieved and subsequent collection of health-related quality of life data occurs at the earliest possible opportunity following commencement of treatment, followed by an adequate number of follow-up assessments.ConclusionTrial-based cost-utility analyses within emergency and critical illness settings have applied different methods for QALY estimation, employing disparate assumptions about the health-related quality of life of patients at baseline. Where baseline measurement is not practical, measurement at the earliest opportunity following commencement of treatment should minimise bias in QALY estimation.