A multidomain decision support tool to prevent falls in older people: the FinCH cluster RCT.

BACKGROUND: Falls in care home residents are common, unpleasant, costly and difficult to prevent. OBJECTIVES: The objectives were to evaluate the clinical effectiveness and cost-effectiveness of the Guide to Action for falls prevention in Care Homes (GtACH) programme. DESIGN: A multicentre, cluster, parallel, 1 : 1 randomised controlled trial with embedded process evaluation and economic evaluation. Care homes were randomised on a 1 : 1 basis to the GtACH programme or usual care using a secure web-based randomisation service. Research assistants, participating residents and staff informants were blind to allocation at recruitment; research assistants were blind to allocation at follow-up. NHS Digital data were extracted blindly. SETTING: Older people's care homes from 10 UK sites. PARTICIPANTS: Older care home residents. INTERVENTION: The GtACH programme, which includes care home staff training, systematic use of a multidomain decision support tool and implementation of falls prevention actions, compared to usual falls prevention care. OUTCOMES: The primary trial outcome was the rate of falls per participating resident occurring during the 90-day period between 91 and 180 days post randomisation. The primary outcome for the cost-effectiveness analysis was the cost per fall averted, and the primary outcome for the cost-utility analysis was the incremental cost per quality adjusted life-year. Secondary outcomes included the rate of falls over days 0-90 and 181-360 post randomisation, activity levels, dependency and fractures. The number of falls per resident was compared between arms using a negative binomial regression model (generalised estimating equation). RESULTS: A total of 84 care homes were randomised: 39 to the GtACH arm and 45 to the control arm. A total of 1657 residents consented and provided baseline measures (mean age 85 years, 32% men). GtACH programme training was delivered to 1051 staff (71% of eligible staff) over 146 group sessions. Primary outcome data were available for 630 GtACH participants and 712 control participants. The primary outcome result showed an unadjusted incidence rate ratio of 0.57 (95% CI 0.45 to 0.71; p < 0.01) in favour of the GtACH programme. Falls rates were lower in the GtACH arm in the period 0-90 days. There were no other differences between arms in the secondary outcomes. Care home staff valued the training, systematic strategies and specialist peer support, but the incorporation of the GtACH programme documentation into routine care home practice was limited. No adverse events were recorded. The incremental cost was £20,889.42 per Dementia Specific Quality of Life-based quality-adjusted life-year and £4543.69 per quality-adjusted life-year based on the EuroQol-5 dimensions, five-level version. The mean number of falls was 1.889 (standard deviation 3.662) in the GtACH arm and 2.747 (standard deviation 7.414) in the control arm. Therefore, 0.858 falls were averted. The base-case incremental cost per fall averted was £190.62. CONCLUSION: The GtACH programme significantly reduced the falls rate in the study care homes without restricting residents' activity levels or increasing their dependency, and was cost-effective at current thresholds in the NHS. FUTURE WORK: Future work should include a broad implementation programme, focusing on scale and sustainability of the GtACH programme. LIMITATIONS: A key limitation was the fact that care home staff were not blinded, although risk was small because of the UK statutory requirement to record falls in care homes. TRIAL REGISTRATION: This trial is registered as ISRCTN34353836. 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. 26, No. 9. See the NIHR Journals Library website for further project information.

Falls in care home residents are common, unpleasant, costly and hard to prevent. We tested whether or not the Guide to Action for falls prevention in Care Homes (GtACH) programme was effective in preventing falls. In this programme, care home staff were systematically trained and supported in the assessment of residents' risk of falling and the generation of a falls reduction care plan. We undertook a randomised controlled trial comparing the GtACH programme with usual care, which does not involve this systematic attention to falls prevention. We also undertook a process evaluation, observing organisational and care processes, and an economic study to evaluate value for money. A total of 39 care homes were randomly allocated to the GtACH programme and 45 care homes were randomly allocated to usual care, involving a total of 1657 residents. The main comparison between the two arms was the rate of falls during months 4­6 after randomisation, when we expected any effect to be at its peak. We also assessed the falls rates before and 6 months after this period. We measured activity and dependency levels, as it was important to be sure that any reduction in the rate of falls was not achieved through restrictive care practices. We saw a 43% reduction in the falls rates of the GtACH programme participants during months 4­6, without observing any reduction in residents' activity or dependency. Care home staff and relatives were positive about the GtACH programme. The GtACH programme was good value for money, as it was likely to be cost-effective. The effect of the programme waned over months 6­12, which may be because some staff did not embed the GtACH programme in their usual practice routines, and awareness levels may have dropped.

Universal late pregnancy ultrasound screening to predict adverse outcomes in nulliparous women: a systematic review and cost-effectiveness analysis.

BACKGROUND: Currently, pregnant women are screened using ultrasound to perform gestational aging, typically at around 12 weeks' gestation, and around the middle of pregnancy. Ultrasound scans thereafter are performed for clinical indications only. OBJECTIVES: We sought to assess the case for offering universal late pregnancy ultrasound to all nulliparous women in the UK. The main questions addressed were the diagnostic effectiveness of universal late pregnancy ultrasound to predict adverse outcomes and the cost-effectiveness of either implementing universal ultrasound or conducting further research in this area. DESIGN: We performed diagnostic test accuracy reviews of five ultrasonic measurements in late pregnancy. We conducted cost-effectiveness and value-of-information analyses of screening for fetal presentation, screening for small for gestational age fetuses and screening for large for gestational age fetuses. Finally, we conducted a survey and a focus group to determine the willingness of women to participate in a future randomised controlled trial. DATA SOURCES: We searched MEDLINE, EMBASE and the Cochrane Library from inception to June 2019. REVIEW METHODS: The protocol for the review was designed a priori and registered. Eligible studies were identified using keywords, with no restrictions for language or location. The risk of bias in studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Health economic modelling employed a decision tree analysed via Monte Carlo simulation. Health outcomes were from the fetal perspective and presented as quality-adjusted life-years. Costs were from the perspective of the public sector, defined as NHS England, and the costs of special educational needs. All costs and quality-adjusted life-years were discounted by 3.5% per annum and the reference case time horizon was 20 years. RESULTS: Umbilical artery Doppler flow velocimetry, cerebroplacental ratio, severe oligohydramnios and borderline oligohydramnios were all either non-predictive or weakly predictive of the risk of neonatal morbidity (summary positive likelihood ratios between 1 and 2) and were all weakly predictive of the risk of delivering a small for gestational age infant (summary positive likelihood ratios between 2 and 4). Suspicion of fetal macrosomia is strongly predictive of the risk of delivering a large infant, but it is only weakly, albeit statistically significantly, predictive of the risk of shoulder dystocia. Very few studies blinded the result of the ultrasound scan and most studies were rated as being at a high risk of bias as a result of treatment paradox, ascertainment bias or iatrogenic harm. Health economic analysis indicated that universal ultrasound for fetal presentation only may be both clinically and economically justified on the basis of existing evidence. Universal ultrasound including fetal biometry was of borderline cost-effectiveness and was sensitive to assumptions. Value-of-information analysis indicated that the parameter that had the largest impact on decision uncertainty was the net difference in cost between an induced delivery and expectant management. LIMITATIONS: The primary literature on the diagnostic effectiveness of ultrasound in late pregnancy is weak. Value-of-information analysis may have underestimated the uncertainty in the literature as it was focused on the internal validity of parameters, which is quantified, whereas the greatest uncertainty may be in the external validity to the research question, which is unquantified. CONCLUSIONS: Universal screening for presentation at term may be justified on the basis of current knowledge. The current literature does not support universal ultrasonic screening for fetal growth disorders. FUTURE WORK: We describe proof-of-principle randomised controlled trials that could better inform the case for screening using ultrasound in late pregnancy. STUDY REGISTRATION: This study is registered as PROSPERO CRD42017064093. 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. 15. See the NIHR Journals Library website for further project information.

Ultrasound scans allow doctors to check on the health of an unborn infant. Usually, all pregnant women receive a scan at about 3 months and about 5 months of pregnancy. After that, women are offered a scan during birth only if they have risk factors or if a problem develops. Problems can arise in the later stages of pregnancy, including issues with the infant's growth or whether or not the infant is breech. Some of these problems may be prevented if a scan is carried out, but scans can also be inaccurate. When they are, a woman may receive unnecessary treatment, which could even harm her or her infant. In this study we set out to review previous research about how good ultrasound scanning is at detecting infants who may be born with a condition. This study focused on detecting if the infant was too big or too small. Unfortunately, much of the previous research was not carried out to a high standard. Scanning can detect the size of a infant relatively well, but it is much less clear if scanning can predict complications that may harm the infant during birth. We also studied the costs and outcomes of scanning. We calculated the extra cost required to scan every woman and compared this with the extra benefits from preventing complications. One thing that ultrasound scans detect is whether the infant is presenting head first or bottom first (a 'breech presentation'), as infants presenting breech have high risks of complications. Scanning all women to check whether or not their infant is presenting breech seems to be cost-effective and the cost savings may even be higher than the cost of implementation, although this depends on how much the scan would cost. Whether or not it is worthwhile scanning all infants to see if they are above or below the thresholds for normal size is less clear. A larger research study could provide more reliable numbers from which to draw a conclusion. We show how such a study could be designed, so that a single study could tell us both how well scans can predict adverse outcomes and how helpful this information is.

Practical help for specifying the target difference in sample size calculations for RCTs: the DELTA2 five-stage study, including a workshop.

BACKGROUND: The randomised controlled trial is widely considered to be the gold standard study for comparing the effectiveness of health interventions. Central to its design is a calculation of the number of participants needed (the sample size) for the trial. The sample size is typically calculated by specifying the magnitude of the difference in the primary outcome between the intervention effects for the population of interest. This difference is called the 'target difference' and should be appropriate for the principal estimand of interest and determined by the primary aim of the study. The target difference between treatments should be considered realistic and/or important by one or more key stakeholder groups. OBJECTIVE: The objective of the report is to provide practical help on the choice of target difference used in the sample size calculation for a randomised controlled trial for researchers and funder representatives. METHODS: The Difference ELicitation in TriAls2 (DELTA2) recommendations and advice were developed through a five-stage process, which included two literature reviews of existing funder guidance and recent methodological literature; a Delphi process to engage with a wider group of stakeholders; a 2-day workshop; and finalising the core document. RESULTS: Advice is provided for definitive trials (Phase III/IV studies). Methods for choosing the target difference are reviewed. To aid those new to the topic, and to encourage better practice, 10 recommendations are made regarding choosing the target difference and undertaking a sample size calculation. Recommended reporting items for trial proposal, protocols and results papers under the conventional approach are also provided. Case studies reflecting different trial designs and covering different conditions are provided. Alternative trial designs and methods for choosing the sample size are also briefly considered. CONCLUSIONS: Choosing an appropriate sample size is crucial if a study is to inform clinical practice. The number of patients recruited into the trial needs to be sufficient to answer the objectives; however, the number should not be higher than necessary to avoid unnecessary burden on patients and wasting precious resources. The choice of the target difference is a key part of this process under the conventional approach to sample size calculations. This document provides advice and recommendations to improve practice and reporting regarding this aspect of trial design. Future work could extend the work to address other less common approaches to the sample size calculations, particularly in terms of appropriate reporting items. FUNDING: Funded by the Medical Research Council (MRC) UK and the National Institute for Health Research as part of the MRC-National Institute for Health Research Methodology Research programme.

This Difference ELicitation in TriAls² (DELTA²) advice and recommendations document aims to help researchers choose the 'target difference' in a type of research study called a randomised controlled trial. The number of people needed to be involved in a study ­ the sample size ­ is usually based on a calculation aimed to ensure that the difference in benefit between treatments is likely to be detected. The calculation also accounts for the risk of a false-positive finding. No more patients than necessary should be involved. Choosing a 'target difference' is an important step in calculating the sample size. The target difference is defined as the amount of difference in the participants' response to the treatments that we wish to detect. It is probably the most important piece of information used in the sample size calculation. How we decide what the target difference should be depends on various factors. One key decision to make is how we should measure the benefits that treatments offer. For example, if we are evaluating a treatment for high blood pressure, the obvious thing to focus on would be blood pressure. We could then proceed to consider what an important difference in blood pressure between treatments would be, based on experts' views or evidence from previous research studies. This document seeks to provide assistance to researchers on how to choose the target difference when designing a trial. It also provides advice to help them clearly present what was done and why, when writing up the study proposal or reporting the study's findings. The document is also intended to be read by those who decide whether or not a proposed study should be funded. Clarifying a study's aim and getting a sensible sample size is important. It can affect not only those involved in the study, but also future patients who will receive treatment.

Surveillance arterioveNous fistulAs using ultRasound (SONAR) trial in haemodialysis patients: a study protocol for a multicentre observational study.

INTRODUCTION: Arteriovenous fistulas (AVFs) are considered the best and safest modality for providing haemodialysis in patients with end-stage renal disease. Only 20% of UK centres achieve the recommended 80% target for achieving dialysis of the prevalent dialysis population via permanent access (as opposed to a central venous catheter). This is partly due to the relatively poor maturation rate of newly created fistulas, with as many as 50% of fistulas failing to mature.The Surveillance Of arterioveNous fistulAe using ultRasound study will examine whether a protocolised programme of Doppler ultrasound (US) surveillance can identify, early after creation, potentially correctable problems in those AVFs that subsequently fail to mature. METHODS AND ANALYSIS: This is a multicentre observational study that will assess newly created AVFs by Doppler US performed at 2, 4, 6 and 10 weeks after creation. The primary outcome measure will be primary fistula patency at week 10. Secondary outcome measures include: successful use of the fistula; clinical suitability for dialysis; creation of new fistula or radiological salvage; fistula thrombosis; secondary fistula patency rate and patient acceptability. ETHICS AND DISSEMINATION: The study has been approved by the Cambridgeshire and Hertfordshire Research Ethics Committee and by the Health Research Authority (REC 18/EE/0234). The results generated from this work will be published as open access, within 3 years of trial commencement. We will also present our findings at key national/international renal meetings, as well as support volunteers at renal patient groups to disseminate the trial outcome. TRIAL REGISTRATION NUMBER: ISRCTN36033877.

PreImplantation Trial of Histopathology In renal Allografts (PITHIA): a stepped-wedge cluster randomised controlled trial protocol.

INTRODUCTION: Most potential kidney transplant donors in the UK are aged over 60 years, yet increasing donor age is associated with poorer graft survival and function. Urgent preimplantation kidney biopsy can identify chronic injury, and may aid selection of better 'quality' kidneys from this group. However, the impact of biopsy on transplant numbers remains unproven. The PreImplantation Trial of Histopathology In renal Allografts (PITHIA) study will assess whether the introduction of a national, 24 hours, digital histopathology service increases the number, and improves outcomes, of kidneys transplanted in the UK from older deceased donors. METHODS AND ANALYSIS: PITHIA is an open, multicentre, stepped-wedge cluster randomised study, involving all UK adult kidney transplant centres. At 4-monthly intervals, a group of 4-5 randomly selected clusters (transplant centres) will be given access to remote, urgent, digital histopathology (total intervention period, 24 months). The trial has two primary end points: it is powered for an 11% increase in the proportion of primary kidney offers from deceased donors aged over 60 years that are transplanted, and a 6 mL/min increase in the estimated glomerular filtration rate of recipients at 12 months post-transplant. This would equate to an additional 120 kidney transplants performed in the UK annually. Trial outcome data will be collected centrally via the UK Transplant Registry held by NHS Blood and Transplant (NHSBT) and will be analysed using mixed effects models allowing for clustering within centres and adjusting for secular trends. An accompanying economic evaluation will estimate the cost-effectiveness of the service to the National Health Service. ETHICS AND DISSEMINATION: The study has been given favourable ethical opinion by the Cambridge South Research Ethics Committee and is approved by the Health Research Authority. We will present our findings at key transplant meetings, publish results within 4 years of the trial commencing and support volunteers at renal patient groups to disseminate the trial outcome. TRIAL REGISTRATION NUMBER: ISRCTN11708741; Pre-results.

Long-Term Costs and Health Consequences of Issuing Shorter Duration Prescriptions for Patients with Chronic Health Conditions in the English NHS.

BACKGROUND: The National Health Service (NHS) in England spends over £9 billion on prescription medicines dispensed in primary care, of which over two-thirds is accounted for by repeat prescriptions. Recently, GPs in England have been urged to limit the duration of repeat prescriptions, where clinically appropriate, to 28 days to reduce wastage and hence contain costs. However, shorter prescriptions will increase transaction costs and thus may not be cost saving. Furthermore, there is evidence to suggest that shorter prescriptions are associated with lower adherence, which would be expected to lead to lower clinical benefit. The objective of this study is to estimate the cost-effectiveness of 3-month versus 28-day repeat prescriptions from the perspective of the NHS. METHODS: We adapted three previously developed UK policy-relevant models, incorporating transaction (dispensing fees, prescriber time) and drug wastage costs associated with 3-month and 28-day prescriptions in three case studies: antihypertensive medications for prevention of cardiovascular events; drugs to improve glycaemic control in patients with type 2 diabetes; and treatments for depression. RESULTS: In all cases, 3-month prescriptions were associated with lower costs and higher QALYs than 28-day prescriptions. This is driven by assumptions that higher adherence leads to improved disease control, lower costs and improved QALYs. CONCLUSION: Longer repeat prescriptions may be cost-effective compared with shorter ones. However, the quality of the evidence base on which this modelling is based is poor. Any policy rollout should be within the context of a trial such as a stepped-wedge cluster design.

Association of psychological distress, quality of life and costs with carpal tunnel syndrome severity: a cross-sectional analysis of the PALMS cohort.

OBJECTIVES: The Prediciting factors for response to treatment in carpal tunnel syndrome (PALMS) study is designed to identify prognostic factors for outcome from corticosteroid injection and surgical decompression for carpal tunnel syndrome (CTS) and predictors of cost over 2 years. The aim of this paper is to explore the cross-sectional association of baseline patient-reported and clinical severity with anxiety, depression, health-related quality of life and costs of CTS in patients referred to secondary care. METHODS: Prospective, multicentre cohort study initiated in 2013. We collected baseline data on patient-reported symptom severity (CTS-6), psychological status (Hospital Anxiety and Depression Scale), hand function (Michigan Hand Questionnaire) comorbidities, EQ-5D-3L (3-level version of EuroQol-5 dimension) and sociodemographic variables. Nerve conduction tests classified patients into five severity grades (mild to very severe). Data were analysed using a general linear model. RESULTS: 753 patients with CTS provided complete baseline data. Multivariable linear regression adjusting for age, sex, ethnicity, duration of CTS, smoking status, alcohol consumption, employment status, body mass index and comorbidities showed a highly statistically significant relationship between CTS-6 and anxiety, depression and the EQ-5D (p<0.0001 in each case). Likewise, a significant relationship was observed between electrodiagnostic severity and anxiety (p=0.027) but not with depression (p=0.986) or the EQ-5D (p=0.257). National Health Service (NHS) and societal costs in the 3 months prior to enrolment were significantly associated with self-reported severity (p<0.0001) but not with electrodiagnostic severity. CONCLUSIONS: Patient-reported symptom severity in CTS is significantly and positively associated with anxiety, depression, health-related quality of life, and NHS and societal costs even when adjusting for age, gender, body mass index, comorbidities, smoking, drinking and occupational status. In contrast, there is little or no evidence of any relationship with objectively derived CTS severity. Future research is needed to understand the impact of approaches and treatments that address psychosocial stressors as well as biomedical factors on relief of symptoms from carpal tunnel syndrome.

A cluster randomised controlled trial to evaluate the effectiveness and cost-effectiveness of the GoActive intervention to increase physical activity among adolescents aged 13-14 years.

INTRODUCTION: Adolescent physical activity promotion is rarely effective, despite adolescence being critical for preventing physical activity decline. Low adolescent physical activity is likely to last into adulthood, increasing health risks. The Get Others Active (GoActive) intervention is evidence-based and was developed iteratively with adolescents and teachers. This intervention aims to increase physical activity through increased peer support, self-efficacy, group cohesion, self-esteem and friendship quality, and is implemented using a tiered-leadership system. We previously established feasibility in one school and conducted a pilot randomised controlled trial (RCT) in three schools. METHODS AND ANALYSIS: We will conduct a school-based cluster RCT (CRCT) in 16 secondary schools targeting all year 9 students (n=2400). In eight schools, GoActive will run for two terms: weekly facilitation support from a council-funded intervention facilitator will be offered in term 1, with more distant support in term 2. Tutor groups choose two weekly activities, encouraged by older adolescent mentors and weekly peer leaders. Students gain points for trying new activities; points are entered into a between-class competition. Outcomes will be assessed at baseline, interim (week 6), postintervention (week 14-16) and 10-month follow-up (main outcome). The primary outcome will be change from baseline in daily accelerometer-assessed moderate-to-vigorous physical activity. Secondary outcomes include accelerometer-assessed activity intensities on weekdays/weekends; self-reported physical activity and psychosocial outcomes; cost-effectiveness and cost-utility analyses; mixed-methods process evaluation integrating information from focus groups and participation logs/questionnaires. ETHICS AND DISSEMINATION: Ethical approval for the conduct of the study was gained from the University of Cambridge Psychology Research Ethics Committee. Given the lack of rigorously evaluated interventions, and the inclusion of objective measurement of physical activity, long-term follow-up and testing of causal pathways, the results of a CRCT of the effectiveness and cost-effectiveness of GoActive are expected to add substantially to the limited evidence on adolescent physical activity promotion. Workshops will be held with key stakeholders including students, parents, teachers, school governors and government representatives to discuss plans for wider dissemination of the intervention. TRIAL REGISTRATION NUMBER: ISRCTN31583496.

A randomised trial of the effect and cost-effectiveness of early intensive multifactorial therapy on 5-year cardiovascular outcomes in individuals with screen-detected type 2 diabetes: the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION-Europe) study.

BACKGROUND: Intensive treatment (IT) of cardiovascular risk factors can halve mortality among people with established type 2 diabetes but the effects of treatment earlier in the disease trajectory are uncertain. OBJECTIVE: To quantify the cost-effectiveness of intensive multifactorial treatment of screen-detected diabetes. DESIGN: Pragmatic, multicentre, cluster-randomised, parallel-group trial. SETTING: Three hundred and forty-three general practices in Denmark, the Netherlands, and Cambridge and Leicester, UK. PARTICIPANTS: Individuals aged 40-69 years with screen-detected diabetes. INTERVENTIONS: Screening plus routine care (RC) according to national guidelines or IT comprising screening and promotion of target-driven intensive management (medication and promotion of healthy lifestyles) of hyperglycaemia, blood pressure and cholesterol. MAIN OUTCOME MEASURES: The primary end point was a composite of first cardiovascular event (cardiovascular mortality/morbidity, revascularisation and non-traumatic amputation) during a mean [standard deviation (SD)] follow-up of 5.3 (1.6) years. Secondary end points were (1) all-cause mortality; (2) microvascular outcomes (kidney function, retinopathy and peripheral neuropathy); and (3) patient-reported outcomes (health status, well-being, quality of life, treatment satisfaction). Economic analyses estimated mean costs (UK 2009/10 prices) and quality-adjusted life-years from an NHS perspective. We extrapolated data to 30 years using the UK Prospective Diabetes Study outcomes model [version 1.3; (©) Isis Innovation Ltd 2010; see www.dtu.ox.ac.uk/outcomesmodel (accessed 27 January 2016)]. RESULTS: We included 3055 (RC, n = 1377; IT, n = 1678) of the 3057 recruited patients [mean (SD) age 60.3 (6.9) years] in intention-to-treat analyses. Prescription of glucose-lowering, antihypertensive and lipid-lowering medication increased in both groups, more so in the IT group than in the RC group. There were clinically important improvements in cardiovascular risk factors in both study groups. Modest but statistically significant differences between groups in reduction in glycated haemoglobin (HbA1c) levels, blood pressure and cholesterol favoured the IT group. The incidence of first cardiovascular event [IT 7.2%, 13.5 per 1000 person-years; RC 8.5%, 15.9 per 1000 person-years; hazard ratio 0.83, 95% confidence interval (CI) 0.65 to 1.05] and all-cause mortality (IT 6.2%, 11.6 per 1000 person-years; RC 6.7%, 12.5 per 1000 person-years; hazard ratio 0.91, 95% CI 0.69 to 1.21) did not differ between groups. At 5 years, albuminuria was present in 22.7% and 24.4% of participants in the IT and RC groups, respectively [odds ratio (OR) 0.87, 95% CI 0.72 to 1.07), retinopathy in 10.2% and 12.1%, respectively (OR 0.84, 95% CI 0.64 to 1.10), and neuropathy in 4.9% and 5.9% (OR 0.95, 95% CI 0.68 to 1.34), respectively. The estimated glomerular filtration rate increased between baseline and follow-up in both groups (IT 4.31 ml/minute; RC 6.44 ml/minute). Health status, well-being, diabetes-specific quality of life and treatment satisfaction did not differ between the groups. The intervention cost £981 per patient and was not cost-effective at costs ≥ £631 per patient. CONCLUSIONS: Compared with RC, IT was associated with modest increases in prescribed treatment, reduced levels of risk factors and non-significant reductions in cardiovascular events, microvascular complications and death over 5 years. IT did not adversely affect patient-reported outcomes. IT was not cost-effective but might be if delivered at a reduced cost. The lower than expected event rate, heterogeneity of intervention delivery between centres and improvements in general practice diabetes care limited the achievable differences in treatment between groups. Further follow-up to assess the legacy effects of early IT is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT00237549. FUNDING DETAILS: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 64. See the NIHR Journals Library website for further project information.

Protocol for the MoleMate UK Trial: a randomised controlled trial of the MoleMate system in the management of pigmented skin lesions in primary care [ISRCTN 79932379].

BACKGROUND: Suspicious pigmented lesions are a common presenting problem in general practice consultations; while the majority are benign a small minority are melanomas. Differentiating melanomas from other pigmented lesions in primary care is challenging: currently, 95% of all lesions referred to a UK specialist are benign. The MoleMate system is a new diagnostic aid, incorporating a hand-held SIAscopy scanner with a primary care diagnostic algorithm. This trial tests the hypothesis that adding the MoleMate system to current best primary care practice will increase the proportion of appropriate referrals of suspicious pigmented lesions to secondary care compared with current best practice alone. METHODS/DESIGN: The MoleMate UK Trial is a primary care based multi-centre randomised controlled trial, with randomisation at patient level using a validated block randomisation method for two age groups (45 years and under; 46 years and over). We aim to recruit adult patients seen in general practice with a pigmented skin lesion that cannot immediately be diagnosed as benign and the patient reassured. The trial has a 'two parallel groups' design, comparing 'best practice' with 'best practice' plus the MoleMate system in the intervention group. The primary outcome is the positive predictive value (PPV) of referral defined as the proportion of referred lesions seen by secondary care experts that are considered 'clinically significant' (i.e. biopsied or monitored). Secondary outcomes include: the sensitivity, specificity and negative predictive value (NPV) of the decision not to refer; clinical outcomes (melanoma thickness, 5 year melanoma incidence and mortality); clinician outcomes (Index of Suspicion, confidence, learning effects); patient outcomes (satisfaction, general and cancer-specific worry), and cost-utility. DISCUSSION: The MoleMate UK Trial tests a new technology designed to improve the management of suspicious pigmented lesions in primary care. If effective, the MoleMate system could reduce the burden on skin cancer clinics of patients with benign pigmented skin lesions, and improve patient care in general practice.

Controlling hypertension immediately post stroke: a cost utility analysis of a pilot randomised controlled trial.

BACKGROUND: Elevated blood pressure (BP) levels are common following acute stroke. However, there is considerable uncertainty if and when antihypertensive therapy should be initiated. METHOD: Economic evaluation alongside a double-blind randomised placebo-controlled trial (National Research Register Trial Number N0484128008) of 112 hypertensive patients receiving an antihypertensive regimen (labetalol or lisinopril) within 36 hours post stroke versus 59 receiving placebo. Outcomes were incremental cost per incremental: QALY, survivor, and patient free from death or severe disability (modified Rankin scale score < 4) at three months and 14 days post stroke. RESULTS: Actively treated patients on average had superior outcomes and lower costs than controls at three months. From the perspective of the acute hospital setting, there was a 96.5% probability that the incremental cost per QALY gained at three months is below pound30,000, although the probability may be overstated due to data limitations. CONCLUSION: Antihypertensive therapy when indicated immediately post stroke may be cost-effective compared with placebo from the acute hospital perspective. Further research is required to confirm both efficacy and cost-effectiveness and establish whether benefits are maintained over a longer time horizon.