SummaryBackgroundTranexamic acid can prevent death due to bleeding after trauma and post-partum haemorrhage. We aimed to assess whether tranexamic acid reduces haematoma expansion and improves outcome in adults with stroke due to intracerebral haemorrhage.MethodsWe did an international, randomised placebo-controlled trial in adults with intracerebral haemorrhage from acute stroke units at 124 hospital sites in 12 countries. Participants were randomly assigned (1:1) to receive 1 g intravenous tranexamic acid bolus followed by an 8 h infusion of 1 g tranexamic acid or a matching placebo, within 8 h of symptom onset. Randomisation was done centrally in real time via a secure website, with stratification by country and minimisation on key prognostic factors. Treatment allocation was concealed from patients, outcome assessors, and all other health-care workers involved in the trial. The primary outcome was functional status at day 90, measured by shift in the modified Rankin Scale, using ordinal logistic regression with adjustment for stratification and minimisation criteria. All analyses were done on an intention-to-treat basis. This trial is registered with the ISRCTN registry, number ISRCTN93732214.FindingsWe recruited 2325 participants between March 1, 2013, and Sept 30, 2017. 1161 patients received tranexamic acid and 1164 received placebo; the treatment groups were well balanced at baseline. The primary outcome was assessed for 2307 (99%) participants. The primary outcome, functional status at day 90, did not differ significantly between the groups (adjusted odds ratio [aOR] 0·88, 95% CI 0·76–1·03, p=0·11). Although there were fewer deaths by day 7 in the tranexamic acid group (101 [9%] deaths in the tranexamic acid group vs 123 [11%] deaths in the placebo group; aOR 0·73, 0·53–0·99, p=0·0406), there was no difference in case fatality at 90 days (250 [22%] vs 249 [21%]; adjusted hazard ratio 0·92, 95% CI 0·77–1·10, p=0·37). Fewer patients had serious adverse events after tranexamic acid than after placebo by days 2 (379 [33%] patients vs 417 [36%] patients), 7 (456 [39%] vs 497 [43%]), and 90 (521 [45%] vs 556 [48%]).InterpretationFunctional status 90 days after intracerebral haemorrhage did not differ significantly between patients who received tranexamic acid and those who received placebo, despite a reduction in early deaths and serious adverse events. Larger randomised trials are needed to confirm or refute a clinically significant treatment effect.FundingNational Institute of Health Research Health Technology Assessment Programme and Swiss Heart Foundation.

BackgroundLung cancer screening using low-dose CT (LDCT) was shown to reduce lung cancer mortality by 20% in the National Lung Screening Trial.MethodsThe pilot UK Lung Cancer Screening (UKLS) is a randomised controlled trial of LDCT screening for lung cancer versus usual care. A population-based questionnaire was used to identify high-risk individuals. CT screen-detected nodules were managed by a pre-specified protocol. Cost effectiveness was modelled with reference to the National Lung Cancer Screening Trial mortality reduction.Results247 354 individuals aged 50–75 years were approached; 30.7% expressed an interest, 8729 (11.5%) were eligible and 4055 were randomised, 2028 into the CT arm (1994 underwent a CT). Forty-two participants (2.1%) had confirmed lung cancer, 34 (1.7%) at baseline and 8 (0.4%) at the 12-month scan. 28/42 (66.7%) had stage I disease, 36/42 (85.7%) had stage I or II disease. 35/42 (83.3%) had surgical resection. 536 subjects had nodules greater than 50 mm3 or 5 mm diameter and 41/536 were found to have lung cancer. One further cancer was detected by follow-up of nodules between 15 and 50 mm3 at 12 months. The baseline estimate for the incremental cost-effectiveness ratio of once-only CT screening, under the UKLS protocol, was £8466 per quality adjusted life year gained (CI £5542 to £12 569).ConclusionsThe UKLS pilot trial demonstrated that it is possible to detect lung cancer at an early stage and deliver potentially curative treatment in over 80% of cases. Health economic analysis suggests that the intervention would be cost effective—this needs to be confirmed using data on observed lung cancer mortality reduction.Trial registrationISRCTN 78513845.

BackgroundLung cancer kills more people than any other cancer in the UK (5-year survival < 13%). Early diagnosis can save lives. The USA-based National Lung Cancer Screening Trial reported a 20% relative reduction in lung cancer mortality and 6.7% all-cause mortality in low-dose computed tomography (LDCT)-screened subjects.ObjectivesTo (1) analyse LDCT lung cancer screening in a high-risk UK population, determine optimum recruitment, screening, reading and care pathway strategies; and (2) assess the psychological consequences and the health-economic implications of screening.DesignA pilot randomised controlled trial comparing intervention with usual care. A population-based risk questionnaire identified individuals who were at high risk of developing lung cancer (≥ 5% over 5 years).SettingThoracic centres with expertise in lung cancer imaging, respiratory medicine, pathology and surgery: Liverpool Heart & Chest Hospital, Merseyside, and Papworth Hospital, Cambridgeshire.ParticipantsIndividuals aged 50–75 years, at high risk of lung cancer, in the primary care trusts adjacent to the centres.InterventionsA thoracic LDCT scan. Follow-up computed tomography (CT) scans as per protocol. Referral to multidisciplinary team clinics was determined by nodule size criteria.Main outcome measuresPopulation-based recruitment based on risk stratification; management of the trial through web-based database; optimal characteristics of CT scan readers (radiologists vs. radiographers); characterisation of CT-detected nodules utilising volumetric analysis; prevalence of lung cancer at baseline; sociodemographic factors affecting participation; psychosocial measures (cancer distress, anxiety, depression, decision satisfaction); and cost-effectiveness modelling.ResultsA total of 247,354 individuals were approached to take part in the trial; 30.7% responded positively to the screening invitation. Recruitment of participants resulted in 2028 in the CT arm and 2027 in the control arm. A total of 1994 participants underwent CT scanning: 42 participants (2.1%) were diagnosed with lung cancer; 36 out of 42 (85.7%) of the screen-detected cancers were identified as stage 1 or 2, and 35 (83.3%) underwent surgical resection as their primary treatment. Lung cancer was more common in the lowest socioeconomic group. Short-term adverse psychosocial consequences were observed in participants who were randomised to the intervention arm and in those who had a major lung abnormality detected, but these differences were modest and temporary. Rollout of screening as a service or design of a full trial would need to address issues of outreach. The health-economic analysis suggests that the intervention could be cost-effective but this needs to be confirmed using data on actual lung cancer mortality.ConclusionsThe UK Lung Cancer Screening (UKLS) pilot was successfully undertaken with 4055 randomised individuals. The data from the UKLS provide evidence that adds to existing data to suggest that lung cancer screening in the UK could potentially be implemented in the 60–75 years age group, selected via the Liverpool Lung Project risk model version 2 and using CT volumetry-based management protocols.Future workThe UKLS data will be pooled with the NELSON (Nederlands Leuvens Longkanker Screenings Onderzoek: Dutch–Belgian Randomised Lung Cancer Screening Trial) and other European Union trials in 2017 which will provide European mortality and cost-effectiveness data. For now, there is a clear need for mortality results from other trials and further research to identify optimal methods of implementation and delivery. Strategies for increasing uptake and providing support for underserved groups will be key to implementation.Trial registrationCurrent Controlled Trials ISRCTN78513845.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 20, No. 40. See the NIHR Journals Library website for further project information.

No abstract

BackgroundThe EQ-5D health-related quality of life instrument comprises a health state classification followed by a health evaluation using a visual analogue scale (VAS). The EQ-5D has been employed frequently in economic evaluations, yet the relationship between the two parts of the instrument remains ill-understood. In this paper, we examine the correspondence between VAS scores and health state classifications for a large sample, and identify variables which contribute to determining the VAS scores independently of the health states as classified.MethodsA UK trial of management of low-grade abnormalities detected on screening for cervical pre-cancer (TOMBOLA) provided EQ-5D data for over 3,000 women. Information on distress and multi-dimensional health locus of control had been collected using other instruments. A linear regression model was fitted, with VAS score as the dependent variable. Independent variables comprised EQ-5D health state classifications, distress, locus of control, and socio-demographic characteristics. Equivalent EQ-5D and distress data, collected at twelve months, were available for over 2,000 of the women, enabling us to predict changes in VAS score over time from changes in EQ-5D classification and distress.ResultsIn addition to EQ-5D health state classification, VAS score was influenced by the subject's perceived locus of control, and by her age, educational attainment, ethnic origin and smoking behaviour. Although the EQ-5D classification includes a distress dimension, the independent measure of distress was an additional determinant of VAS score. Changes in VAS score over time were explained by changes in both EQ-5D severities and distress. Women allocated to the experimental management arm of the trial reported an increase in VAS score, independently of any changes in health state and distress.ConclusionIn this sample, EQ VAS scores were predictable from the EQ-5D health state classification, although there also existed other group variables which contributed systematically and independently towards determining such scores. These variables comprised psychological disposition, socio-demographic factors such as age and education, clinically-important distress, and the clinical intervention itself.Trial registrationISRCTN34841617