ObjectivesPrevention of type 2 diabetes mellitus (TD2M) is a priority for healthcare systems. We estimated the cost-effectiveness compared with standard care of a structured education programme (Let's Prevent) targeting lifestyle and behaviour change to prevent progression to T2DM in people with prediabetes.DesignCost-effectiveness analysis alongside randomised controlled trial.Setting44 general practices in Leicestershire, England.Participants880 participants with prediabetes randomised to receive either standard care or a 6-hour group structured education programme with follow-up sessions in a primary care setting.Main outcome measureIncremental cost utility from the UK National Health Service (NHS) perspective. Quality of life and resource use measured from baseline and during the 36 months follow-up using the EuroQoL EQ-5D and 15D instruments and an economic questionnaire. Outcomes measured using quality-adjusted life years (QALYs) and healthcare costs calculated in 2012–2013 prices.ResultsAfter accounting for clustering and missing data, the intervention group was found to have a net gain of 0.046 (95% CI −0.0171 to 0.109) QALYs over 3 years, adjusted for baseline utility, at an additional cost of £168 (95% CI −395 to 732) per patient compared with the standard care group. The incremental cost-effectiveness ratio is £3643/QALY with an 86% probability of being cost-effective at a willingness to pay threshold of £20 000/QALY.ConclusionsThe education programme had higher costs and higher quality of life compared with the standard care group. The Let's Prevent programme is very likely to be cost-effective at a willingness to pay threshold of £20 000/QALY gained.Trial registration numberISRCTN80605705.

BackgroundPrevention of type 2 diabetes mellitus (T2DM) is a global priority; however, there is a lack of evidence investigating how to effectively translate prevention research into a primary care setting.Objectives(1) To develop and validate a risk score to identify individuals at high risk of T2DM in the UK; and (2) to establish whether or not a structured education programme targeting lifestyle and behaviour change was clinically effective and cost-effective at preventing progression to T2DM in people with prediabetes mellitus (PDM), identified through a risk score screening programme in primary care.DesignA targeted screening study followed by a cluster randomised controlled trial (RCT), with randomisation at practice level. Participants were followed up for 3 years.SettingA total of 44 general practices across Leicestershire, UK. The intervention took place in the community.ParticipantsA total of 17,972 individuals from 44 practices identified through the risk score as being at high risk of T2DM were invited for screening; of these, 3449 (19.2%) individuals attended. All received an oral glucose tolerance test. PDM was detected in 880 (25.5%) of those screened. Those with PDM were included in the trial; of these, 36% were female, the average age was 64 years and 16% were from an ethnic minority group.InterventionPractices were randomised to receive either standard care or the intervention. The intervention consisted of a 6-hour group structured education programme, with an annual refresher and regular telephone contact.Main outcome measuresThe primary outcome was progression to T2DM. The main secondary outcomes were changes in glycated haemoglobin concentrations, blood glucose levels, cardiovascular risk, the presence of metabolic syndrome, step count and the cost-effectiveness of the intervention.ResultsA total of 22.6% of the intervention group did not attend the education and 29.1% attended all sessions. A total of 131 participants developed T2DM (standard care,n = 67; intervention,n = 64). There was a 26% reduced risk of T2DM in the intervention arm compared with standard care, but this did not reach statistical significance (hazard ratio 0.74, 95% confidence interval 0.48 to 1.14;p = 0.18). There were statistically significant improvements in glycated haemoglobin concentrations, low-density lipoprotein cholesterol levels, psychosocial well-being, sedentary time and step count in the intervention group. The intervention was found to result in a net gain of 0.046 quality-adjusted life-years over 3 years at a cost of £168 per patient, with an incremental cost-effectiveness ratio of £3643 and a probability of 0.86 of being cost-effective at a willingness-to-pay threshold of £20,000.ConclusionsWe developed and validated a risk score for detecting those at high risk of undiagnosed PDM/T2DM. We screened > 3400 people using a two-stage screening programme. The RCT showed that a relatively low-resource pragmatic programme may lead to a reduction in T2DM and improved biomedical and psychosocial outcomes, and is cost-effective.LimitationsOnly 19% of those invited to screening attended, which may limit generalisability. The variation in cluster size in the RCT may have limited the power of the study.Future workFuture work should focus on increasing attendance to both screening and prevention programmes and offering the programme in different modalities, such as web-based modalities. A longer-term follow-up of the RCT participants would be valuable.Trial registrationCurrent Controlled Trials ISRCTN80605705.FundingThe National Institute for Health Research Programme Grants for Applied Research programme.

Alemtuzumab infusion is rarely associated with serious cardiac toxicity. We report a case of acute troponin-negative chest pain with dynamic T-wave changes, immediately following first infusion of alemtuzumab in a patient with multiple sclerosis. The chest pain and ECG (electrocardiogram) changes improved with cessation of alemtuzumab and conservative management. The presumed cause was infusion-associated cytokine release, but the precise mechanism is unknown.

BackgroundDaclizumab is an anti-CD25 monoclonal antibody developed for the treatment of relapsing remitting multiple sclerosis, which was withdrawn worldwide in March 2018, due to emerging serious immune-mediated systemic andcentral nervous system adverse events. We report a case of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis occurring 14 weeks after stopping daclizumab, which responded to the proteasome inhibitor bortezomib.MethodsFollowing lack of effective clinical response to first line (corticosteroid, plasma exchange, intravenous immunoglobulin) and second line (rituximab) treatments, bortezomib therapy was commenced. The patient received six cycles of bortezomib treatment.ResultsClinical improvement was noted 4 weeks after the first of six cycles of bortezomib and the patient experienced sustained clinical improvement.ConclusionOur case provides further class IV evidence of the use of bortezomib therapy for treatment refractory anti-NMDAR encephalitis.