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Levetiracetam and zonisamide are licensed as monotherapy for patients with focal epilepsy, but there is uncertainty as to whether they should be recommended as first-line treatments because of insufficient evidence of clinical effectiveness and cost-effectiveness. We aimed to assess the long-term clinical effectiveness and cost-effectiveness of levetiracetam and zonisamide compared with lamotrigine in people with newly diagnosed focal epilepsy.

Valproate is a first-line treatment for patients with newly diagnosed idiopathic generalised or difficult to classify epilepsy, but not for women of child-bearing potential because of teratogenicity. Levetiracetam is increasingly prescribed for these patient populations despite scarcity of evidence of clinical effectiveness or cost-effectiveness. We aimed to compare the long-term clinical effectiveness and cost-effectiveness of levetiracetam compared with valproate in participants with newly diagnosed generalised or unclassifiable epilepsy.

Insertion of a ventriculoperitoneal shunt for hydrocephalus is one of the commonest neurosurgical procedures worldwide. Infection of the implanted shunt affects up to 15% of these patients, resulting in prolonged hospital treatment, multiple surgeries, and reduced cognition and quality of life. Our aim was to determine the clinical and cost-effectiveness of antibiotic (rifampicin and clindamycin) or silver shunts compared with standard shunts at reducing infection.

ObjectivesTo describe the early impact of COVID-19 and associated control measures on the sexual behaviour of pre-exposure prophylaxis (PrEP) users in Wales.MethodsData were obtained from an ecological momentary assessment study of PrEP use and sexual behaviour. Participants were individuals accessing PrEP through the National Health Service (NHS) sexual health clinics across four health boards in Wales. Weekly data documenting condomless sex in the preceding week were analysed between 03/02/2020 and 10/05/2020. The introduction of social distancing measures and changes to sexual health clinics in Wales occurred on the week starting 16/03/2020. Two-level logistic regression models were fitted to condomless sex (yes/no) over time, included an indicator for the week starting 16/03/2020, and were extended to explore differential associations by relationship status and sexual health clinic.ResultsData were available from 56 participants and included 697 person-weeks (89% of the maximum number that could have been obtained). On average, 42% of participants reported condomless sex in the period prior to the introduction of social distancing measures and 20% reported condomless sex after (OR=0.16, 95% CI 0.07 to 0.37, p<0.001). There was some evidence to suggest that this association was moderated by relationship status (OR for single participants=0.09, 95% CI 0.06 to 0.23; OR for not single participants=0.46, 95% CI 0.16 to 1.25).ConclusionsThe introduction of social distancing measures and changes to PrEP services across Wales was associated with a marked reduction in reported instances of condomless sexual intercourse among respondents, with a larger reduction in those who were single compared with those who were not. The long-term impact of COVID-19 and associated control measures on this population’s physical and mental health and well-being requires close examination.

Pharmacogenetic tests are being used increasingly to prevent rare and potentially life-threatening adverse drug reactions. For many tests, however, cost–effectiveness is hard to demonstrate, and with the exception of a few cases, widespread implementation remains a distant prospect. Many orphan drugs for rare diseases are also not cost effective but are nonetheless normally reimbursed. In this article, we argue that the health technology assessment of pharmacogenetic tests aimed to prevent rare but severe adverse drug reactions should be on a level playing field with orphan drugs. This is supported by a number of arguments, concerning the severity, rarity and iatrogenic nature of adverse drug reactions, the distribution of benefits and costs and societal preference towards prevention over treatment.

Cochrane Reviews summarise best evidence and should inform guidelines. We assessed the use of Cochrane Reviews in the UK guidelines for paediatric respiratory disease. We found 21 guidelines which made 1025 recommendations, of which 96 could be informed by a Cochrane Review. In 38/96 recommendations (40%), some or all of the relevant Cochrane Reviews were not cited. We linked recommendations to 140 Cochrane Reviews. In 37/140 (26%) cases, the guideline recommendation did not fully agree with the Cochrane Review. Guideline developers may fail to use Cochrane Reviews or may make recommendations which are not in line with best evidence.

To estimate the cost of managing drug-related morbidity (DRM) that leads to visits to the emergency department of a Brazilian hospital.

Impregnated central venous catheters are recommended for adults to reduce bloodstream infections but not for children because there is not enough evidence to prove they are effective. We aimed to assess the effectiveness of any type of impregnation (antibiotic or heparin) compared with standard central venous catheters to prevent bloodstream infections in children needing intensive care.

In this prospective cohort study, we have undertaken a comprehensive evaluation of clinical parameters along with variation in 29 genes (including CYP2C9 and VKORC1) to identify factors determining interindividual variability in warfarin response.

On-demand proton pump inhibitor maintenance therapy is one of the suggested strategies for patients with nonerosive gastroesophageal reflux disease who achieve symptom remission after 4 weeks of continuous treatment. This review evaluates the difference in cost and quality of life of six on-demand proton pump inhibitor maintenance strategies in patients with nonerosive gastroesophageal reflux disease. This was performed by decision analysis and Markov modeling of costs (from the perspective of the healthcare service and society) and utility up to 12 months. Median utility scores associated with each proton pump inhibitor ranged from 0.731 to 0.745 quality-adjusted life years and were not statistically different. Annual expected cost, however, was statistically different among the different drugs and the following cost-minimization ranking was obtained for median costs to the healthcare service and society, respectively: rabeprazole (€181, €295), pantoprazole (€223, €341), lansoprazole (€249, €370), omeprazole 10 mg (€297, €412), esomeprazole (€295, €419) and omeprazole 20 mg (€405, €528). Unit cost of proton pump inhibitors was the major determinant of cost to the healthcare service, while the number of productivity days lost due to symptoms was the major determinant of cost to society. In Italy, on-demand use of rabeprazole for maintenance therapy of nonerosive gastroesophageal reflux disease incurs the least cost in comparison with the other proton pump inhibitors evaluated.

Abacavir, a human immunodeficiency virus-1 (HIV-1) nucleoside-analogue reverse transcriptase inhibitor, causes severe hypersensitivity in 4–8% of patients. HLA B5701is a known genetic risk factor for abacavir hypersensitivity in Caucasians. Our aim was to confirm the presence of this genetic factor in our patients, and to determine whether genotyping for HLA B5701would be a cost-effective use of healthcare resources.

Poor compliance with prescribed drug regimens is a widespread phenomenon which results in decreased efficacy and is often associated with increased medical expenditures due to treatment failure and/or adverse events. This review examines the issues relating to the measurement of compliance and the clinical and economic consequences of noncompliant drug taking behavior. The results of a literature review, identifying pharmacoeconomic evaluations which measured compliance, are presented. It concludes by highlighting the importance of accounting for poor compliance in pharmacoeconomic evaluations and suggests ways in which compliance may be incorporated in economic models.

Non‐compliance with drug therapies not only limits their effectiveness, but in some instances, is associated with grave clinical sequelae and substantial economic burden. It is important, therefore, to consider non‐compliance in economic evaluations. A review of pharmacoeconomic evaluations, which have applied sensitivity analysis to non‐compliance rates, was undertaken to evaluate the impact of non‐compliance on the cost‐effectiveness of different drug therapies. Although 22 evaluations satisfied the inclusion criteria, additional information was obtained from the authors of most studies, as the published details were inadequate. The majority of evaluations assumed altered effectiveness owing to reduced compliance in the absence of supportive clinical evidence. Because of the disparity in the nature of the outcomes, the measures of non‐compliance and the time horizon of the studies evaluated, it was not possible to compare the magnitude of the impact of non‐compliance among different drug–disease combinations. However, it was evident that non‐compliance always results in a reduction in efficacy, but its impact on costs varied substantially. The importance of incorporating measures of compliance is highlighted, as failing to account for ‘real world’ compliance rates in pharmacoeconomic evaluations may lead to selection of sub‐optimal treatment strategies. Copyright © 2001 John Wiley & Sons, Ltd.

The presentation in a meaningful way of the data from large-scale and/or longterm current-meter stations is difficult. It is suggested here that a very useful statistic in this field is the ratio of the Vector Mean to the Scalar Mean of a currentmeter record expressed as a percentage. It is proposed that the new statistic should be called the Neumann factor and examples of ways in which it is already being used routinely are given. Two of its limitations are also pointed out.

ObjectivesTo identify preferences for outcomes of antiepileptic drugs (AEDs) that patients consider important and, to investigate the impact of patient preferences on the ranking of AEDs, as indicated by a clinical trial.MethodsAdult patients with epilepsy completed a web-based questionnaire containing a discrete choice experiment. Patients made choices between hypothetical pairs of AEDs described by varying levels of clinical efficacy and treatment-related adverse events (AEs). Data were analysed using a random effects logit model. Women with the potential to become pregnant were analysed separately. Utility and probability of uptake for existing AEDs were derived using preference weights and published clinical event data.ResultsPatients (n=414) had stronger preferences for reducing the risk of AEs than improving treatment benefit. In return for a 1% improvement in 12 month remission, the maximum acceptable risk of adverse events was: depression 0.31%, memory problems 0.30%, aggression 0.25%; and for women with the potential to become pregnant: depression 0.56%, memory problems 0.34%, and foetal abnormality 0.20%. The rank ordering of AEDs differed when patient preferences were considered.ConclusionExploring what patients consider important in measuring AED effectiveness will assist in supporting adherence, and ensure clinical services are focused on patient-defined needs.

ObjectiveTo compare the efficacy, safety, and cost utility of continuous subcutaneous insulin infusion (CSII) with multiple daily injection (MDI) regimens during the first year following diagnosis of type 1 diabetes in children and young people.DesignPragmatic, multicentre, open label, parallel group, randomised controlled trial and economic evaluation.Setting15 paediatric National Health Service (NHS) diabetes services in England and Wales. The study opened to recruitment in May 2011 and closed in January 2017.ParticipantsPatients aged between 7 months and 15 years, with a new diagnosis of type 1 diabetes were eligible to participate. Patients who had a sibling with the disease, and those who took drug treatments or had additional diagnoses that could have affected glycaemic control were ineligible.InterventionsParticipants were randomised, stratified by age and treating centre, to start treatment with CSII or MDI within 14 days of diagnosis. Starting doses of aspart (CSII and MDI) and glargine or detemir (MDI) were calculated according to weight and age, and titrated according to blood glucose measurements and according to local clinical practice.Main outcome measuresPrimary outcome was glycaemic control (as measured by glycated haemoglobin; HbA1c) at 12 months. Secondary outcomes were percentage of patients in each treatment arm with HbA1c within the national target range, incidence of severe hypoglycaemia and diabetic ketoacidosis, change in height and body mass index (as measured by standard deviation scores), insulin requirements (units/kg/day), partial remission rate (insulin dose adjusted HbA1c <9), paediatric quality of life inventory score, and cost utility based on the incremental cost per quality adjusted life year (QALY) gained from an NHS costing perspective.Results294 participants were randomised and 293 included in intention to treat analyses (CSI, n=144; MDI, n=149). At 12 months, mean HbA1c was comparable with clinically unimportant differences between CSII and MDI participants (60.9 mmol/mol v58.5 mmol/mol, mean difference 2.4 mmol/mol (95% confidence interval −0.4 to 5.3), P=0.09). Achievement of HbA1c lower than 58 mmol/mol was low among the two groups (66/143 (46%) CSII participants v78/142 (55%) MDI participants; relative risk 0.84 (95% confidence interval 0.67 to 1.06)). Incidence of severe hypoglycaemia and diabetic ketoacidosis were low in both groups. Fifty four non-serious and 14 serious adverse events were reported during CSII treatment, and 17 non-serious and eight serious adverse events during MDI treatment. Parents (but not children) reported superior PedsQL scores for those patients treated with CSII compared to those treated with MDI. CSII was more expensive than MDI by £1863 (€2179; $2474; 95% confidence interval £1620 to £2137) per patient, with no additional QALY gains (difference −0.006 (95% confidence interval −0.031 to 0.018)).ConclusionDuring the first year following type 1 diabetes diagnosis, no clinical benefit of CSII over MDI was identified in children and young people in the UK setting, and treatment with either regimen was suboptimal in achieving HbA1c thresholds. CSII was not cost effective.Trial registrationCurrent Controlled Trials ISRCTN29255275; European Clinical Trials Database 2010-023792-25.

IntroductionWhilst the majority of seriously ill people express a wish to die at home (79%), only half of those achieve this. The likelihood of patients remaining at home often depends on availability of able and willing informal carers who take on numerous care tasks, often including the responsibility of assisting patients with oral medications. The role of carers administering subcutaneous injections is not widespread practice in the UK, but has proven to be key in achieving home death in other countries.AimTo determine if carer-administration of as-needed subcutaneous medication for four breakthrough symptoms (pain, nausea, restlessness and noisy breathing) in homebased dying patients is feasible and acceptable in the UK.MethodsOne hundred adult patients in the last weeks of life who are likely to lose the oral route and have expressed a preference to die at home will be recruited with their carers to an external randomised pilot trial across three UK sites (North Wales, South Wales and Gloucestershire). Carers randomised to the intervention arm will receive a manualised training package adapted from an existing Australian model and delivered by local district nursing teams. Dyads in the control arm will receive usual care.ResultsThe main outcomes of interest will be feasibility, acceptability, recruitment rates, attrition and selection of the most appropriate outcomes measures.ConclusionFindings will inform a definitive Phase III randomised controlled trial.The study is funded by the National Institute for Health Research (HTA project 15/10/37). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

There are a number of clinical and non-clinical administrative datasets that routinely record information on individuals in the UK. Access for secondary uses such as clinical research is permitted when health and social care benefit can be demonstrated. Clinical sources of data are commonly accessed to provide data for retrospective observational and record-linkage studies and provide a valid dataset for this purpose. Routinely recorded data may also present advantages to prospective clinical research such as randomised controlled trials (RCTs). The majority of RCTs incur health service costs as clinicians assess participants, record outcomes and complete Case Report Forms – hence using routinely recorded data may provide an efficient alternative method for data collection in addition to reducing the burden on participants. Furthermore, data from non-clinical routine sources may inform outcomes beyond the standard RCT assessments of clinical efficacy and effectiveness. However, limitations with accuracy of coding, confidentiality, ownership and access have previously been identified as significant barriers. This study has assessed the feasibility of accessing clinical and non-clinical routinely recorded data during a RCT assessing treatments for newly diagnosed epilepsy and will assess the agreement and additional benefits of routinely recorded data compared to data collected using standard prospective methods.

OBJECTIVE:s To determine the incremental net health benefits of dabigatran etexilate 110 mg and 150 mg twice daily and warfarin in patients with non-valvular atrial fibrillation and to estimate the cost effectiveness of dabigatran in the United Kingdom. Design Quantitative benefit-harm and economic analyses using a discrete event simulation model to extrapolate the findings of the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) study to a lifetime horizon. Setting UK National Health Service. Population Cohorts of 50 000 simulated patients at moderate to high risk of stroke with a mean baseline CHADS2(Congestive heart failure, Hypertension, Age≥75 years, Diabetes mellitus, previous Stroke/transient ischaemic attack) score of 2.1. MAIN OUTCOME MEASURES: Quality adjusted life years (QALYs) gained and incremental cost per QALY of dabigatran compared with warfarin. RESULTS: Compared with warfarin, low dose and high dose dabigatran were associated with positive incremental net benefits of 0.094 (95% central range –0.083 to 0.267) and 0.146 (–0.029 to 0.322) QALYs. Positive incremental net benefits resulted for high dose dabigatran in 94% of simulations versus warfarin and in 76% of those versus low dose dabigatran. In the economic analysis, high dose dabigatran dominated the low dose, had an incremental cost effectiveness ratio of £23 082 (€26 700; $35 800) per QALY gained versus warfarin, and was more cost effective in patients with a baseline CHADS2score of 3 or above. However, at centres that achieved good control of international normalised ratio, such as those in the UK, dabigatran 150 mg was not cost effective, at £42 386 per QALY gained. CONCLUSIONS: This analysis supports regulatory decisions that dabigatran offers a positive benefit to harm ratio when compared with warfarin. However, no subgroup for which dabigatran 110 mg offered any clinical or economic advantage over 150 mg was identified. High dose dabigatran will be cost effective only forpatients at increased risk of stroke or for whom international normalised ratio is likely to be less well controlled.

OBJECTIVE: To investigate the cost effectiveness of a parenting programme. Design An incremental cost effectiveness analysis alongside a pragmatic randomised controlled trial of the effectiveness of a group parenting programme delivered through Sure Start in the community. Setting Sure Start areas in north and mid Wales. Participants Parents of 116 children aged 36-59 months (87% of the clinical sample) at risk of developing conduct disorders defined by scoring over the clinical cut off on the Eyberg child behaviour inventory). Children were identified by health visitors and recruited by the research team. Intervention The Webster-Stratton Incredible Years basic parenting programme or a six month waiting list control. MAIN OUTCOME MEASURE: Incremental cost per unit of improvement on the intensity score of the Eyberg child behaviour inventory. RESULTS: The bootstrapped incremental cost effectiveness ratio point estimate was £73 (€109, $142) per one point improvement on the intensity score (95% confidence interval £42 to £140). It would cost £5486 (€8190, $10 666) to bring the child with the highest intensity score to below the clinical cut-off point and £1344 (€2006, $2618) to bring the average child in the intervention group within the non-clinical limits on the intensity score (below 127). For a ceiling ratio of £100 (€149, $194) per point increase in intensity score, there is an 83.9% chance of the intervention being cost effective. The mean cost per child attending the parenting group was £1934 (€2887, $3760) for eight children and £1289 (€1924, $2506) for 12 children, including initial costs and materials for training group leaders. When we categorised the sample into relatively mild, moderate, and severe behaviour groups based on intensity scores at baseline the intervention seemed more cost effective in those with the highest risk of developing conduct disorder. CONCLUSION: This parenting programme improves child behaviour as measured by the intensity score of the Eyberg child behaviour inventory at a relatively low cost and was cost effective compared with the waiting list control. This parenting programme involves modest costs and demonstrates strong clinical effect, suggesting it would represent good value for money for public spending.