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Background Early research in adults admitted to intensive care suggested that tight control of blood glucose during acute illness can be associated with reductions in mortality, length of hospital stay and complications such as infection and renal failure. Prior to our study, it was unclear whether or not children could also benefit from tight control of blood glucose during critical illness. Objectives This study aimed to determine if controlling blood glucose using insulin in paediatric intensive care units (PICUs) reduces mortality and morbidity and is cost-effective, whether or not admission follows cardiac surgery. Design Randomised open two-arm parallel group superiority design with central randomisation with minimisation. Analysis was on an intention-to-treat basis. Following random allocation, care givers and outcome assessors were no longer blind to allocation. Setting The setting was 13 English PICUs. Participants Patients who met the following criteria were eligible for inclusion: ≥ 36 weeks corrected gestational age; ≤ 16 years; in the PICU following injury, following major surgery or with critical illness; anticipated treatment > 12 hours; arterial line; mechanical ventilation; and vasoactive drugs. Exclusion criteria were as follows: diabetes mellitus; inborn error of metabolism; treatment withdrawal considered; in the PICU > 5 consecutive days; and already in CHiP (Control of Hyperglycaemia in Paediatric intensive care). Intervention The intervention was tight glycaemic control (TGC): insulin by intravenous infusion titrated to maintain blood glucose between 4.0 and 7.0 mmol/l. Conventional management (CM) This consisted of insulin by intravenous infusion only if blood glucose exceeded 12.0 mmol/l on two samples at least 30 minutes apart; insulin was stopped when blood glucose fell below 10.0 mmol/l. Main outcome measures The primary outcome was the number of days alive and free from mechanical ventilation within 30 days of trial entry (VFD-30). The secondary outcomes comprised clinical and economic outcomes at 30 days and 12 months and lifetime cost-effectiveness, which included costs per quality-adjusted life-year. Results CHiP recruited from May 2008 to September 2011. In total, 19,924 children were screened and 1369 eligible patients were randomised (TGC, 694; CM, 675), 60% of whom were in the cardiac surgery stratum. The randomised groups were comparable at trial entry. More children in the TGC than in the CM arm received insulin (66% vs. 16%). The mean VFD-30 was 23 [mean difference 0.36; 95% confidence interval (CI) –0.42 to 1.14]. The effect did not differ among prespecified subgroups. Hypoglycaemia occurred significantly more often in the TGC than in the CM arm (moderate, 12.5% vs. 3.1%; severe, 7.3% vs. 1.5%). Mean 30-day costs were similar between arms, but mean 12-month costs were lower in the TGC than in CM arm (incremental costs –£3620, 95% CI –£7743 to £502). For the non-cardiac surgery stratum, mean costs were lower in the TGC than in the CM arm (incremental cost –£9865, 95% CI –£18,558 to –£1172), but, in the cardiac surgery stratum, the costs were similar between the arms (incremental cost £133, 95% CI –£3568 to £3833). Lifetime incremental net benefits were positive overall (£3346, 95% CI –£11,203 to £17,894), but close to zero for the cardiac surgery stratum (–£919, 95% CI –£16,661 to £14,823). For the non-cardiac surgery stratum, the incremental net benefits were high (£11,322, 95% CI –£15,791 to £38,615). The probability that TGC is cost-effective is relatively high for the non-cardiac surgery stratum, but, for the cardiac surgery subgroup, the probability that TGC is cost-effective is around 0.5. Sensitivity analyses showed that the results were robust to a range of alternative assumptions. Conclusions CHiP found no differences in the clinical or cost-effectiveness of TGC compared with CM overall, or for prespecified subgroups. A higher proportion of the TGC arm had hypoglycaemia. This study did not provide any evidence to suggest that PICUs should stop providing CM for children admitted to PICUs following cardiac surgery. For the subgroup not admitted for cardiac surgery, TGC reduced average costs at 12 months and is likely to be cost-effective. Further research is required to refine the TGC protocol to minimise the risk of hypoglycaemic episodes and assess the long-term health benefits of TGC. Trial registration Current Controlled Trials ISRCTN61735247. Funding This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 26. See the NIHR Journals Library website for further project information.

Background Cost-benefit analysis is a transparent tool to inform policy makers about the potential effect of regulatory interventions, nevertheless its use to evaluate clean-up interventions in polluted industrial sites is limited. The two industrial areas of Gela and Priolo in Italy were declared "at high risk of environmental crisis" in 1990. Since then little has been done to clean the polluted sites and reduce the health outcomes attributable to pollution exposure. This study, aims to quantify the monetary benefits resulting from clean-up interventions in the contaminated sites of Gela and Priolo. Methods A damage function approach was used to estimate the number of health outcomes attributable to industrial pollution exposure. Extensive one way analyses and probabilistic analyses were conducted to investigate the sensitivity of results to different model assumptions. Results It has been estimated that, on average, 47 cases of premature death, 281 cases of cancer and 2,702 cases of non-cancer hospital admission could be avoided each year by removing environmental exposure in these two areas. Assuming a 20 year cessation lag and a 4% discount rate we calculate that the potential monetary benefit of removing industrial pollution is €3,592 million in Priolo and €6,639 million in Gela. Conclusions Given the annual number of health outcomes attributable to pollution exposure the effective clean-up of Gela and Priolo should be prioritised. This study suggests that clean-up policies costing up to €6,639 million in Gela and €3,592 million in Priolo would be cost beneficial. These two amounts are notably higher than the funds allocated thus far to clean up the two sites, €127.4 million in Gela and €774.5 million in Priolo, implying that further economic investments - even considerable ones - could still prove cost beneficial.

ObjectiveTo assess the cost effectiveness of giving tranexamic acid (TXA) to bleeding trauma patients in low, middle and high income settings.MethodsThe CRASH-2 trial showed that TXA administration reduces the risk of death in bleeding trauma patients with a small but statistically significant increase in non-intensive care stay. A Markov model was used to assess the cost effectiveness of TXA in Tanzania, India and the United Kingdom (UK). The health outcome was the number of life years gained (LYs). Two costs were considered: the cost of administering TXA and the cost of additional days in hospital. Cost data were obtained from hospitals, World Health Organization (WHO) database and UK reference costs. Cost-effectiveness was measured in international dollars ($) per LY. Both deterministic and probabilistic sensitivity analyses were performed to test the robustness of the results to model assumptions.FindingsAdministering TXA to bleeding trauma patients within three hours of injury saved an estimated 372, 315 and 755 LYs per 1,000 trauma patients in Tanzania, India and the UK respectively. The cost of giving TXA to 1,000 patients was $17,483 in Tanzania, $19,550 in India and $30,830 in the UK. The incremental cost of giving TXA versus not giving TXA was $18,025 in Tanzania, $20,670 in India and $48,002 in the UK. The estimated incremental cost per LY gained of administering TXA is $48, $66 and $64 in Tanzania, India and the UK respectively.ConclusionEarly administration of TXA to bleeding trauma patients is likely to be highly cost effective in low, middle and high income settings.Trial registrationThis paper uses data collected by the CRASH 2 trial: Controlled-Trials.com ISRCTN86750102, Clinicaltrials.govNCT00375258 and South African Clinical Trial Register DOH-27-0607-1919.

Three decades of illegal practices of waste dumping and consequent environmental abuse have made the Campania region of Southern Italy a unique case in the context of waste-related health outcomes. Scientific evidence is mounting in support of a significant increase in cancer mortality and malformation occurrence in specific areas of the Campania region, where improper waste management and illegal waste trafficking have been repeatedly documented. However, the currently available evidence suffers from limitations mainly due to study design, lack of consideration of confounders and quality of the exposure data. Recent economic studies have shown the economic benefits of reclaiming toxic waste sites in Campania. Future perspectives include the adoption of different study designs, use of biomarkers and a molecular approach. Current knowledge, both scientific and economic, might be of help in orienting the short and long term governmental policy on waste related health outcomes at a regional level.

Background Single reading with computer aided detection (CAD) is an alternative to double reading for detecting cancer in screening mammograms. The aim of this study is to investigate whether the use of a single reader with CAD is more cost-effective than double reading. Methods Based on data from the CADET II study, the cost-effectiveness of single reading with CAD versus double reading was measured in terms of cost per cancer detected. Cost (Pound (£), year 2007/08) of single reading with CAD versus double reading was estimated assuming a health and social service perspective and a 7 year time horizon. As the equipment cost varies according to the unit size a separate analysis was conducted for high, average and low volume screening units. One-way sensitivity analyses were performed by varying the reading time, equipment and assessment cost, recall rate and reader qualification. Results CAD is cost increasing for all sizes of screening unit. The introduction of CAD is cost-increasing compared to double reading because the cost of CAD equipment, staff training and the higher assessment cost associated with CAD are greater than the saving in reading costs. The introduction of single reading with CAD, in place of double reading, would produce an additional cost of £227 and £253 per 1,000 women screened in high and average volume units respectively. In low volume screening units, the high cost of purchasing the equipment will results in an additional cost of £590 per 1,000 women screened. One-way sensitivity analysis showed that the factors having the greatest effect on the cost-effectiveness of CAD with single reading compared with double reading were the reading time and the reader's professional qualification (radiologist versus advanced practitioner). Conclusions Without improvements in CAD effectiveness (e.g. a decrease in the recall rate) CAD is unlikely to be a cost effective alternative to double reading for mammography screening in UK. This study provides updated estimates of CAD costs in a full-field digital system and assessment cost for women who are re-called after initial screening. However, the model is highly sensitive to various parameters e.g. reading time, reader qualification, and equipment cost.

BACKGROUND: Blood transfusions carry the risk of transmitting infections. This risk has been studied in detail in high-income countries but not in sub-Saharan Africa. This study estimates the risks of acquiring human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) from a single unit of blood in sub-Saharan Africa. STUDY DESIGN AND METHODS: A mathematical model was constructed to quantify transfusion risks across 45 sub-Saharan African countries using three components: the risk of a contaminated unit entering the blood supply, the risk that the unit will be given to a susceptible patient, and the risk that receipt of the unit will lead to infection in the recipient. Variables included prevalence of infection in donors, extent of blood testing, test sensitivity, and susceptibility of recipients. Data from the World Health Organization (WHO) African Region and a systematic review of the literature were used to parameterize the model. Uncertainty in the risk estimates was quantified using probabilistic sensitivity analysis. RESULTS: The median overall risks of becoming infected with HIV, HBV, and HCV from a blood transfusion in sub-Saharan Africa were 1, 4.3, and 2.5 infections per 1000 units, respectively. If annual transfusion requirements projected by the WHO were met, transfusions alone would be responsible for 28,595 HBV infections, 16,625 HCV infections, and 6650 HIV infections every year. Sensitivity analysis suggests that the true risks may be even higher. CONCLUSIONS: This study is the first to systematically quantify the risks of transfusion-transmitted infections across sub-Saharan Africa. Although the results are limited by the quality and quantity of available data, these may be the most reliable estimates at this time.

Background The identification of safe and effective alternatives to blood transfusion is a public health priority. In sub-Saharan Africa, blood shortage is a cause of mortality and morbidity. Blood transfusion can also transmit viral infections. Giving tranexamic acid (TXA) to bleeding surgical patients has been shown to reduce both the number of blood transfusions and the volume of blood transfused. The objective of this study is to investigate whether routinely administering TXA to bleeding elective surgical patients is cost effective by both averting deaths occurring from the shortage of blood, and by preventing infections from blood transfusions. Methods A decision tree was constructed to evaluate the cost-effectiveness of providing TXA compared with no TXA in patients with surgical bleeding in four African countries with different human immunodeficiency virus (HIV) prevalence and blood donation rates (Kenya, South Africa, Tanzania and Botswana). The principal outcome measures were cost per life saved and cost per infection averted (HIV, Hepatitis B, Hepatitis C) averted in 2007 International dollars ($). The probability of receiving a blood transfusion with and without TXA and the risk of blood borne viral infection were estimated. The impact of uncertainty in model parameters was explored using one-way deterministic sensitivity analyses. Probabilistic sensitivity analysis was performed using Monte Carlo simulation. Results The incremental cost per life saved is $87 for Kenya and $93 for Tanzania. In Botswana and South Africa, TXA administration is not life saving but is highly cost saving since fewer units of blood are transfused. Further, in Botswana the administration of TXA averts one case of HIV and four cases of Hepatitis B (HBV) per 1,000 surgical patients. In South Africa, one case of HBV is averted per 1,000 surgical patients. Probabilistic sensitivity analyses confirmed the robustness of the model. Conclusion An economic argument can be made for giving TXA to bleeding elective surgical patients. In countries where there is a blood shortage, TXA would be a cost effective way to reduce mortality. In countries where there is no blood shortage, TXA would reduce healthcare costs and avert blood borne infections.