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Background\ud Previous studies suggest that physical exercise could slow dementia progression. However, evidence for the cost effectiveness of structured exercise is conflicting and based on small trials.\ud \ud Objectives\ud The objective of this study was to compare the cost effectiveness of a tailored, structured, moderate- to high-intensity exercise programme versus usual care in people with mild to moderate dementia.\ud \ud Methods\ud An economic evaluation was conducted from the UK National Health Service and personal social services perspective, based on data from a large randomised controlled trial. The primary clinical outcome was the participant reported ADAS-Cog (Alzheimer’s Disease Assessment Scale–Cognitive Subscale) at 12 months. Costs (£; 2014–2015 prices) were collected prospectively over a 12-month follow-up period. A bivariate regression of costs and quality-adjusted life-years (QALYs), with multiple imputation of missing data, was conducted with the view to estimating the incremental cost per QALY gained and the incremental net monetary benefit (INMB) associated with the exercise programme plus usual care versus usual care. Sensitivity analyses were undertaken to assess the impact of uncertainty surrounding aspects of the economic evaluation, and pre-specified subgroup analyses explored heterogeneity in the cost-effectiveness results.\ud \ud Results\ud Participants (n = 494) were randomised to exercise plus usual care or usual care only. By 12 months the mean ADAS-Cog score had worsened slightly to 25.2 (standard deviation [SD] 12.3) in the exercise arm and 23.8 (SD 10.4) in the usual care: difference − 1.4, 95% confidence interval (CI) − 2.6 to − 0.2 (p = 0.03). The mean (standard error [SE]) costs over 12 months for experimental versus control was £5945 (US$7856) versus £4597 (US$6574), respectively; (difference: £1347 [$1926]; p = 0.0426). Mean (SE) QALY estimates were 0.787 (0.012) versus 0.826 (0.019), respectively (p = 0.090). The probability that the exercise programme is cost effective was

\ud \ud Background Despite extensive knowledge on the functional, neurodevelopmental, behavioural and educational sequelae of preterm birth, relatively little is known about its economic consequences.\ud \ud Objective \ud \ud To systematically review evidence around the economic consequences of preterm birth for the health services, for other sectors of the economy, for families and carers, and more broadly for society.\ud \ud Methods \ud \ud Updating previous reviews, systematic searches of Medline, EconLit, Web of Science, the Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Embase and Scopus were performed using broad search terms, covering the literature from 1 January 2009 to 28 June 2017. Studies reporting economic consequences, published in the English language and conducted in a developed country were included. Economic consequences are presented in a descriptive manner according to study time horizon, cost category and differential denominators (live births or survivors).\ud \ud Results \ud \ud Of 4384 unique articles retrieved, 43 articles met the inclusion criteria. Of these, 27 reported resource use or cost estimates associated with the initial period of hospitalisation, while 26 reported resource use or costs incurred following the initial hospital discharge, 10 of which also reported resource use or costs associated with the initial period of hospitalisation. Only two studies reported resource use or costs incurred throughout the childhood years. Initial hospitalisation costs varied between $576 972 (range $111 152–$576 972) per infant born at 24 weeks’ gestation and $930 (range $930–$7114) per infant born at term (US$, 2015 prices). The review also revealed a consistent inverse association between gestational age at birth and economic costs regardless of date of publication, country of publication, underpinning study design, follow-up period, age of assessment or costing approach, and a paucity of evidence on non-healthcare costs. Several categories of economic costs, such as additional costs borne by families as a result of modifications to their everyday activities, are largely overlooked by this body of literature. Moreover, the number and coverage of economic assessments have not increased in comparison with previous review periods.\ud \ud Conclusion \ud \ud Evidence identified by this review can be used to inform clinical and budgetary service planning and act as data inputs into future economic evaluations of preventive or treatment interventions. Future research should focus particularly on valuing the economic consequences of preterm birth in adulthood.

ObjectiveTo undertake a comprehensive assessment of the strength of preferences among young people for attributes of emerging technologies for testing and treatment of asymptomatic chlamydia.DesignDiscrete choice experiment (DCE) with sequential mixed methods design. A staged approach to selection of attributes/levels included two literature reviews, focus groups with young people aged 16–24 years (n=21), experts’ review (n=13) and narrative synthesis. Cognitive testing was undertaken to pilot and adapt the initial questionnaire. Online national panel was used for final DCE survey to maximise generalisability. Analysis of questionnaire responses used multinomial logit models and included validity checks.SettingEngland.Participants1230 young people aged 16–24 from a national online panel (completion rate 73%).Outcome measuresORs for service attributes in relation to reference levels.ResultsThe strongest attribute influencing preferences was chlamydia test accuracy (OR 3.24, 95% CI 3.13 to 3.36), followed by time to result (OR 1.81, 95% CI 1.71 to 1.91). Respondents showed a preference for remote chlamydia testing options (self-testing, self-sampling and postal testing) over attendance at a testing location. For accessing treatment following a positive test result, there was a general preference for online (OR 1.21, 95% CI 1.15 to 1.28) versus traditional general practitioner (OR 1.18, 95% CI 1.12 to 1.24) or pharmacy (OR 1.15, 95% CI 1.10 to 1.22) over clinic services. For accessing a healthcare professional and receipt of antibiotics, there was little difference in preferences between options.ConclusionsBoth test accuracy and very short intervals between testing and results were important factors for young people when deciding whether to undergo a routine test for asymptomatic chlamydia, with test accuracy being more important. These findings should assist technology developers, policymakers, commissioners and service providers to optimise technology adoption in service redesign, although use of an online panel may limit generalisability of findings to other populations.

Appendix S1. A detailed overview of the key assumptions underpinning the epidemiological model employed in the paper. (PDF 70 kb)

Table S2. Vaccine uptake in the UK, 2008â 2016. (PDF 746 kb)

Figure S1 and Table S6. Parameter distributions. (PDF 176 kb)

Table S3. Efficacy of the three HPV vaccines against different HPV types. (PDF 48 kb)

This supplementary file contains detailed statistical approaches used to analyse the data, additional results for individual disease conditions and sensitivity analysis exploring the impact of fitting different counterfactual models and adjusting the time when vaccinesâ effect is started in the time series analysis (DOCX 747 kb)

Table S5. Costs and health utility decrements. (PDF 55 kb)

Objective To investigate the variation in severe neonatal morbidity among very preterm (VPT) infants across European regions and whether morbidity rates are higher in regions with low compared with high mortality rates. Design Area-based cohort study of all births before 32 weeks of gestational age. Setting 16 regions in 11 European countries in 2011/2012. Patients Survivors to discharge from neonatal care (n=6422). Main outcome measures Severe neonatal morbidity was defined as intraventricular haemorrhage grades III and IV, cystic periventricular leukomalacia, surgical necrotizing enterocolitis and retinopathy of prematurity grades >= 3. A secondary outcome included severe bronchopulmonary dysplasia (BPD), data available in 14 regions. Common definitions for neonatal morbidities were established before data abstraction from medical records. Regional severe neonatal morbidity rates were correlated with regional in-hospital mortality rates for live births after adjustment on maternal and neonatal characteristics. Results 10.6% of survivors had a severe neonatal morbidity without severe BPD (regional range 6.4%23.5%) and 13.8% including severe BPD (regional range 10.0%-23.5%). Adjusted inhospital mortality was 13.7% (regional range 8.4%-18.8%). Differences between regions remained significant after consideration of maternal and neonatal characteristics (P< 0.001) and severe neonatal morbidity rates were not correlated with mortality rates (P= 0.50). Conclusion Severe neonatal morbidity rates for VPT survivors varied widely across European regions and were independent of mortality rates.

Appendix S2. Economic model assumptions. (PDF 40 kb)

Figures S2 and S3. Comparing HPV prevalence between the model and data. (PDF 328 kb)

International audience; OBJECTIVE: To investigate the variation in severe neonatal morbidity among very preterm (VPT) infants across European regions and whether morbidity rates are higher in regions with low compared with high mortality rates.METHODS: Area-based cohort study of all births before 32 weeks of gestational age.METHODS: 16 regions in 11 European countries in 2011/2012.METHODS: Survivors to discharge from neonatal care (n=6422).METHODS: Severe neonatal morbidity was defined as intraventricular haemorrhage grades III and IV, cystic periventricular leukomalacia, surgical necrotizing enterocolitis and retinopathy of prematurity grades ≥3. A secondary outcome included severe bronchopulmonary dysplasia (BPD), data available in 14 regions. Common definitions for neonatal morbidities were established before data abstraction from medical records. Regional severe neonatal morbidity rates were correlated with regional in-hospital mortality rates for live births after adjustment on maternal and neonatal characteristics.RESULTS: 10.6% of survivors had a severe neonatal morbidity without severe BPD (regional range 6.4%-23.5%) and 13.8% including severe BPD (regional range 10.0%-23.5%). Adjusted inhospital mortality was 13.7% (regional range 8.4%-18.8%). Differences between regions remained significant after consideration of maternal and neonatal characteristics (P

Table S4. Clinical parameter values and sources. (PDF 50 kb)

Background\ud \ud Concern about the use of epinephrine as a treatment for out-of-hospital cardiac arrest led the International Liaison Committee on Resuscitation to call for a placebo-controlled trial to determine whether the use of epinephrine is safe and effective in such patients.\ud \ud Methods\ud \ud In a randomized, double-blind trial involving 8014 patients with out-of-hospital cardiac arrest in the United Kingdom, paramedics at five National Health Service ambulance services administered either parenteral epinephrine (4015 patients) or saline placebo (3999 patients), along with standard care. The primary outcome was the rate of survival at 30 days. Secondary outcomes included the rate of survival until hospital discharge with a favorable neurologic outcome, as indicated by a score of 3 or less on the modified Rankin scale (which ranges from 0 [no symptoms] to 6 [death]).\ud \ud Results\ud \ud At 30 days, 130 patients (3.2%) in the epinephrine group and 94 (2.4%) in the placebo group were alive (unadjusted odds ratio for survival, 1.39; 95% confidence interval [CI], 1.06 to 1.82; P=0.02). There was no evidence of a significant difference in the proportion of patients who survived until hospital discharge with a favorable neurologic outcome (87 of 4007 patients [2.2%] vs. 74 of 3994 patients [1.9%]; unadjusted odds ratio, 1.18; 95% CI, 0.86 to 1.61). At the time of hospital discharge, severe neurologic impairment (a score of 4 or 5 on the modified Rankin scale) had occurred in more of the survivors in the epinephrine group than in the placebo group (39 of 126 patients [31.0%] vs. 16 of 90 patients [17.8%]).\ud \ud Conclusions\ud \ud In adults with out-of-hospital cardiac arrest, the use of epinephrine resulted in a significantly higher rate of 30-day survival than the use of placebo, but there was no significant between-group difference in the rate of a favorable neurologic outcome because more survivors had severe neurologic impairment in the epinephrine group. (Funded by the U.K. National Institute for Health Research and others; Current Controlled Trials number, ISRCTN73485024.)\ud

Background and aims\ud \ud Little is known about the long-term economic consequences of smoking during pregnancy. We estimated the association between smoking in pregnancy and the costs of delivering health-care to infants and children in England, and investigated which aspects of care are the key drivers of these costs.\ud \ud Methods\ud \ud We used Hospital Episode Statistics (HES) linked with Clinical Practice Research Datalink (CPRD) data in England from January 2003 to January 2015 in children with longitudinal data for at least 1, 5 and 10 years after birth. Poisson regression provided rate ratios (RR) and 95% confidence intervals (CIs) comparing health-care episode rates between those exposed and not exposed to smoking during pregnancy. Linear regression was used to compare estimated costs between groups (£ sterling, 2015 prices) and generalized linear multivariable (GLM) models adjusted for potentially moderating factors.\ud \ud Results\ud \ud A total of 93 152 singleton pregnancies with the required data were identified. Maternal smoking in pregnancy was associated with higher primary care, prescription and hospital in-patient episode rates, but lower out-patient visit and diagnostic test rates. Adjusting for year of birth, socio-economic deprivation, parity, sex of child and delivery method showed that maternal smoking in pregnancy was associated with increased child health-care costs at 1 year [average cost difference for children of smokers, β = £91.18, 95% confidence interval (CI) = £47.52–134.83 and 5 years of age (β = £221.80, 95% CI = £17.78–425.83], but not at 10 years of age (β = £365.94, 95% CI = –£192.72 to £924.60).\ud \ud Conclusion\ud \ud In England, maternal smoking in pregnancy is associated with increased child health-care costs over the first 5 years of life; these costs are driven primarily by greater hospital in-patient care.

INTRODUCTION: Hyperglycaemia is common in the very preterm infant and has been associated with adverse outcomes. Preventing hyperglycaemia without increasing the risk of hypoglycaemia has proved challenging. The development of real-time continuous glucose monitors (CGM) to inform treatment decisions provides an opportunity to reduce this risk. This study aims to assess the feasibility of CGM combined with a specifically designed paper guideline to target glucose control in the preterm infant. METHODS AND ANALYSES: The Real Time Continuous Glucose Monitoring in Neonatal Intensive Care (REACT) trial is an international multicentre randomised controlled trial. 200 preterm infants ≤1200 g and ≤24 hours of age will be randomly allocated to either real-time CGM or standard care (with blinded CGM data collection). The primary outcome is time in target 2.6-10 mmol/L during the study intervention assessed using CGM. Secondary outcomes include efficacy relating to glucose control, utility including staff acceptability, safety outcomes relating to incidence and prevalence of hypoglycaemia and health economic analyses. ETHICS AND DISSEMINATION: The REACT trial has been approved by the National Health Service Health Research Authority National Research Ethics Service Committee East of England (Cambridge Central); Medical Ethics Review Committee, VU University Medical Centre, Amsterdam, The Netherlands and the Research Ethics Committee, Sant Joan de Déu Research Foundation, Barcelona, Spain. Recruitment began in July 2016 and will continue until mid-2018. The trial has been adopted by the National Institute of Health Research Clinical Research Network portfolio (ID: 18826) and is registered with anInternational Standard Randomised Control Number (ISRCTN registry ID: 12793535). Dissemination plans include presentations at scientific conferences, scientific publications and efforts at stakeholder engagement. TRIAL REGISTRATION NUMBER: ISRCTN12793535; Pre-results.

Purpose Venous thromboembolism (VTE) is common in patients with cancer. Long-term daily subcutaneous low molecular weight heparin has been standard treatment for such patients. The purpose of this study was to assess if an oral factor Xa inhibitor, rivaroxaban, would offer an alternative treatment for VTE in patients with cancer. Patient and Methods In this multicenter, randomized, open-label, pilot trial in the United Kingdom, patients with active cancer who had symptomatic pulmonary embolism (PE), incidental PE, or symptomatic lower-extremity proximal deep vein thrombosis (DVT) were recruited. Allocation was to dalteparin (200 IU/kg daily during month 1, then 150 IU/kg daily for months 2-6) or rivaroxaban (15 mg twice daily for 3 weeks, then 20 mg once daily for a total of 6 months). The primary outcome was VTE recurrence over 6 months. Safety was assessed by major bleeding and clinically relevant nonmajor bleeding (CRNMB). A sample size of 400 patients would provide estimates of VTE recurrence to within ± 4.5%, assuming a VTE recurrence rate at 6 months of 10%. Results A total of 203 patients were randomly assigned to each group, 58% of whom had metastases. Twenty-six patients experienced recurrent VTE (dalteparin, n = 18; rivaroxaban, n = 8). The 6-month cumulative VTE recurrence rate was 11% (95% CI, 7% to 16%) with dalteparin and 4% (95% CI, 2% to 9%) with rivaroxaban (hazard ratio [HR], 0.43; 95% CI, 0.19 to 0.99). The 6-month cumulative rate of major bleeding was 4% (95% CI, 2% to 8%) for dalteparin and 6% (95% CI, 3% to 11%) for rivaroxaban (HR, 1.83; 95% CI, 0.68 to 4.96). Corresponding rates of CRNMB were 4% (95% CI, 2% to 9%) and 13% (95% CI, 9% to 19%), respectively (HR, 3.76; 95% CI, 1.63 to 8.69). Conclusion Rivaroxaban was associated with relatively low VTE recurrence but higher CRNMB compared with dalteparin.