Hypothermia for perinatal asphyxia: trial-based resource use and costs at 6-7 years.

OBJECTIVE: To assess the impact of hypothermic neural rescue for perinatal asphyxia at birth on healthcare costs of survivors aged 6-7 years, and to quantify the relationship between costs and overall disability levels. DESIGN: 6-7 years follow-up of surviving children from the Total Body Hypothermia for Neonatal Encephalopathy (TOBY) trial. SETTING: Community study including a single parental questionnaire to collect information on children's healthcare resource use. PATIENTS: 130 UK children (63 in the control group, 67 in the hypothermia group) whose parents consented and returned the questionnaire. INTERVENTIONS: Intensive care with cooling of the body to 33.5°C for 72 hours or intensive care alone. MAIN OUTCOME MEASURES: Healthcare resource usage and costs over the preceding 6 months. RESULTS: At 6-7 years, mean (SE) healthcare costs per child were £1543 (£361) in the hypothermia group and £2549 (£812) in the control group, giving a saving of -£1005 (95% CI -£2734 to £724). Greater levels of overall disability were associated with progressively higher costs, and more parents in the hypothermia group were employed (64% vs 47%). Results were sensitive to outlying observations. CONCLUSIONS: Cost results although not significant favoured moderate hypothermia and so complement the clinical results of the TOBY Children study. Estimates were however sensitive to the care requirements of two seriously ill children in the control group. A quantification of the relationship between costs and levels of disability experienced will be useful to healthcare professionals, policy makers and health economists contemplating the long-term economic consequences of perinatal asphyxia and hypothermic neural rescue. TRIAL REGISTRATION NUMBER: This study reports on the follow-up of the TOBY clinical trial: ClinicalTrials. gov number NCT01092637.

Hypothermia for perinatal asphyxia: trial-based quality of life at 6-7 years.

OBJECTIVE: To assess the impact of hypothermic neural rescue at birth on health-related quality of life (HRQL) in middle childhood. DESIGN: Six-year to 7-year follow-up of surviving children from the Total Body Hypothermia for Neonatal Encephalopathy (TOBY) Trial. SETTING: Community study including a single parental questionnaire to collect information on children's HRQL. PATIENTS: 145 children (70 in the control group, 75 in the hypothermia group) whose parents consented and returned the questionnaire. INTERVENTIONS: Intensive care with cooling of the body to 33.5°C for 72 hours or intensive care alone. MAIN OUTCOME MEASURES: HRQL attributes and utility scores using the Health Utilities Index (HUI). RESULTS: At 6-7 years, speech appeared disproportionately affected when compared with other aspects of HRQL but levels of normal emotional functioning were similar in both groups. The mean (SE) HUI3 HRQL scores were 0.73 (0.05) in the hypothermia group and 0.62 (0.06) in the control group; mean difference (95% CI) 0.11 (-0.04 to 0.26). CONCLUSIONS: Findings of non-significant differences were not unexpected; the study used data from long-term survivors in a neonatal trial and was underpowered. However, results favoured moderate hypothermia and so complement the clinical results of the TOBY Children study. The work provides further insight into the long-term HRQL impact of perinatal asphyxial encephalopathy and provides previously unavailable utility data with which to contemplate the longer term cost-effectiveness of hypothermic neural rescue. TRIAL REGISTRATION NUMBER: This study reports on the follow-up of the TOBY clinical trial: ClinicalTrials.gov number NCT01092637.

Effect of MRI on preterm infants and their families: a randomised trial with nested diagnostic and economic evaluation.

BACKGROUND: We tested the hypothesis that routine MRI would improve the care and well-being of preterm infants and their families. DESIGN: Parallel-group randomised trial (1.1 allocation; intention-to-treat) with nested diagnostic and cost evaluations (EudraCT 2009-011602-42). SETTING: Participants from 14 London hospitals, imaged at a single centre. PATIENTS: 511 infants born before 33 weeks gestation underwent both MRI and ultrasound around term. 255 were randomly allocated (siblings together) to receive only MRI results and 255 only ultrasound from a paediatrician unaware of unallocated results; one withdrew before allocation. MAIN OUTCOME MEASURES: Maternal anxiety, measured by the State-Trait Anxiety inventory (STAI) assessed in 206/214 mothers receiving MRI and 217/220 receiving ultrasound. Secondary outcomes included: prediction of neurodevelopment, health-related costs and quality of life. RESULTS: After MRI, STAI fell from 36.81 (95% CI 35.18 to 38.44) to 32.77 (95% CI 31.54 to 34.01), 31.87 (95% CI 30.63 to 33.12) and 31.82 (95% CI 30.65 to 33.00) at 14 days, 12 and 20 months, respectively. STAI fell less after ultrasound: from 37.59 (95% CI 36.00 to 39.18) to 33.97 (95% CI 32.78 to 35.17), 33.43 (95% CI 32.22 to 34.63) and 33.63 (95% CI 32.49 to 34.77), p=0.02. There were no differences in health-related quality of life. MRI predicted moderate or severe functional motor impairment at 20 months slightly better than ultrasound (area under the receiver operator characteristic curve (CI) 0.74; 0.66 to 0.83 vs 0.64; 0.56 to 0.72, p=0.01) but cost £315 (CI £295-£336) more per infant. CONCLUSIONS: MRI increased costs and provided only modest benefits. TRIAL REGISTRATION: ClinicalTrials.gov NCT01049594 https://clinicaltrials.gov/ct2/show/NCT01049594. EudraCT: EudraCT: 2009-011602-42 (https://www.clinicaltrialsregister.eu/).

Effects of hypothermia for perinatal asphyxia on childhood outcomes.

BACKGROUND: In the Total Body Hypothermia for Neonatal Encephalopathy Trial (TOBY), newborns with asphyxial encephalopathy who received hypothermic therapy had improved neurologic outcomes at 18 months of age, but it is uncertain whether such therapy results in longer-term neurocognitive benefits. METHODS: We randomly assigned 325 newborns with asphyxial encephalopathy who were born at a gestational age of 36 weeks or more to receive standard care alone (control) or standard care with hypothermia to a rectal temperature of 33 to 34°C for 72 hours within 6 hours after birth. We evaluated the neurocognitive function of these children at 6 to 7 years of age. The primary outcome of this analysis was the frequency of survival with an IQ score of 85 or higher. RESULTS: A total of 75 of 145 children (52%) in the hypothermia group versus 52 of 132 (39%) in the control group survived with an IQ score of 85 or more (relative risk, 1.31; P=0.04). The proportions of children who died were similar in the hypothermia group and the control group (29% and 30%, respectively). More children in the hypothermia group than in the control group survived without neurologic abnormalities (65 of 145 [45%] vs. 37 of 132 [28%]; relative risk, 1.60; 95% confidence interval, 1.15 to 2.22). Among survivors, children in the hypothermia group, as compared with those in the control group, had significant reductions in the risk of cerebral palsy (21% vs. 36%, P=0.03) and the risk of moderate or severe disability (22% vs. 37%, P=0.03); they also had significantly better motor-function scores. There was no significant between-group difference in parental assessments of children's health status and in results on 10 of 11 psychometric tests. CONCLUSIONS: Moderate hypothermia after perinatal asphyxia resulted in improved neurocognitive outcomes in middle childhood. (Funded by the United Kingdom Medical Research Council and others; TOBY ClinicalTrials.gov number, NCT01092637.).

Patient isolation measures for infants with candida colonization or infection for preventing or reducing transmission of candida in neonatal units.

BACKGROUND: Candida is a common nosocomial infection and is associated with increased healthcare costs. In neonates, candida infection is associated with high mortality and morbidity and is transmitted by direct and indirect contact. Patient isolation measures, i.e. single room isolation or cohorting, are usually recommended for infections that spread by contact. OBJECTIVES: To determine the effect of patient isolation measures (single room isolation and/or cohorting) for infants with candida colonization or infection as an adjunct to routine infection control measures on the transmission of candida to other infants in the neonatal unit. SEARCH METHODS: Relevant trials in any language were searched in the following databases in July 2011: The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2011), MEDLINE, BIOSIS, EMBASE and CINAHL. Proceedings of the Pediatric Academic Societies (from 1987) and ongoing trials were searched. SELECTION CRITERIA: Types of studies: Cluster randomized trials (where clusters may be defined by hospital, ward, or other subunits of the hospital). TYPES OF PARTICIPANTS: Neonatal units caring for infants colonized or infected with Candida. Types of interventions: A policy of patient isolation measures (single room isolation or cohorting of infants with Candida colonization or infection) compared to routine isolation measures. DATA COLLECTION AND ANALYSIS: The standard methods of the Cochrane Neonatal Review Group (CNRG) were used to identify studies and to assess the methodological quality of eligible cluster-randomized trials. Infection rates and colonization rates were to be expressed as rate ratios for each trial and if appropriate for meta-analysis, the generic inverse variance method in RevMan was to be used. MAIN RESULTS: No eligible trials were identified. AUTHORS' CONCLUSIONS: The review found no evidence to either support or refute the use of patient isolation measures (single room isolation or cohorting) in neonates with candida colonization or infection.Despite the evidence for transmission of candida by contact and evidence of cross-infection by health care workers, no standard policy of patient isolation measures beyond routine infection control measures exists in the neonatal unit. There is an urgent need to research the role of patient isolation measures for preventing transmission of candida in the neonatal unit. Well designed trials randomizing clusters of units or hospitals to a type of patient isolation method intervention are needed.

A structured review of the recent literature on the economic consequences of preterm birth.

Although survival rates for preterm infants have greatly improved over the last three to four decades, these infants remain at risk of developing a broad range of short-term and long-term complications. Despite the large body of work on the clinical sequelae of preterm birth, relatively little is known about its economic consequences. This paper represents a structured review of the recent scientific literature on 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. A total of 2497 studies were identified by a pretested literature search strategy, 52 of which were included in the final review. Of these 52 studies, 19 reported the costs associated with the initial period of hospitalisation, 35 reported costs incurred following the initial hospital discharge (without providing costs for the entire remaining period of childhood), four of which also reported costs associated with the initial period of hospitalisation, while two reported costs incurred throughout childhood. The paper highlights the variable methodological quality of this body of literature. The results of the studies included in the review are summarised and critically appraised. The paper also highlights gaps in our current knowledge of the topic and identifies requirements for further research in this area.

Cost-effectiveness of therapeutic hypothermia to treat neonatal encephalopathy.

OBJECTIVE: To estimate the cost-effectiveness (CE) of total body hypothermia plus intensive care versus intensive care alone to treat neonatal encephalopathy. METHODS: Decision analytic modeling was used to synthesize mortality and morbidity data from three randomized controlled trials, the Total Body Hypothermia for Neonatal Encephalopathy Trial (TOBY), National Institute of Child Health and Human Development (NICHD), and CoolCap trials. Cost data inputs were informed by TOBY, the sole source of prospectively collected resource utilization data for encephalopathic infants. CE was expressed in terms of incremental cost per disability-free life year (DFLY) gained. Probabilistic sensitivity analysis was performed to generate CE acceptability curves (CEACs). RESULTS: Cooling led to a cost increase of £3787 (95% confidence interval [CI]: -2516, 12,360) (€5115; 95% CI: -3398-16,694; US$5344; 95% CI: -3598, 26,356; using 2006 Organisation for Economic Co-operation and Development (OECD) purchasing power parities) and a DFLY gain of 0.19 (95%CI: 0.07-0.31) over the first 18 months after birth. The incremental cost per DFLY gained was £19,931 (€26,920; US$28,124). The baseline CEAC showed that if decision-makers are willing to pay £30,000 for an additional DFLY, there is a 69% probability that cooling is cost-effective. The probability of CE exceeded 99% at this threshold when the throughput of infants was increased to reflect the national incidence of neonatal encephalopathy or when the time horizon of the economic evaluation was extended to 18 years after birth. CONCLUSIONS: The probability that cooling is a cost-effective treatment for neonatal encephalopathy is finely balanced over the first 18 months after birth but increases substantially when national incidence data or an extended time horizon are considered.

Study of progesterone for the prevention of preterm birth in twins (STOPPIT): findings from a trial-based cost-effectiveness analysis.

OBJECTIVES: Preterm birth contributes to a range of healthcare problems amongst infants surmounting to sizeable healthcare costs. Twin pregnancies are at particular risk of preterm birth. The objective of this study was to assess the cost-effectiveness of vaginal progesterone gel for the prevention of preterm birth in twin pregnancies. METHODS: An economic evaluation was conducted alongside a randomized placebo controlled trial (the STOPPIT trial) of vaginal progesterone gel for the prevention of preterm birth in twin pregnancies. Five hundred women were recruited from nine maternity hospitals in the United Kingdom. The outcomes of the economic evaluation were presented in terms of net benefit statistics, cost-effectiveness acceptability curves, generated using the nonparametric bootstrap method, and the expected value of perfect information. RESULTS: Mean health service costs between the period of randomization and discharge for mother and infant were 28,031 pound sterling in the progesterone group and 25,972 pound sterling in the placebo group, generating a mean nonsignificant cost difference of 2,059 pound sterling (bootstrap mean cost difference 2,334 pound sterling; 95 percent confidence interval: -5,023 pound sterling, 9,142 pound sterling; p = .33). The probability of progesterone being cost-effective was 20 percent at a willingness to pay threshold of 30,000 pound sterling per preterm birth prevented. There is little economic justification for conducting further research into the use of vaginal progesterone gel in twin pregnancies for the prevention of preterm birth. CONCLUSIONS: Further studies of preventive interventions for preterm birth more generally are required given the scale of the clinical and economic burden of this condition. These studies should be sufficiently powered for economic endpoints and extend beyond hospital discharge.

Use of economic evaluation in local health care decision-making in England: a qualitative investigation.

OBJECTIVE: To explore decision-making and the use of economic evaluation at the local health care decision-making level in England (UK). METHODS: Data collection was over a 16-month period (January 2003 to April 2004). Data collection comprised 29 in-depth interviews with a range of decision makers, 13 observations of decision-making meetings, and analysis of documents produced at meetings. A constant comparative approach was used to identify broad themes and sub-themes arising from the data. Data were analysed using Microsoft Word. RESULTS: National Institute for Health and Clinical Excellence (NICE) guidance provides the main way in which economic evaluation is used at a local level in the UK, although following NICE guidance is often regarded as detrimental to pursuing local priorities. Other than through NICE, economic evaluation is not considered at the local level; we found no evidence for use at the meeting group (by individuals). Although decision makers appear to understand notions of scarcity, with some also referring to value for money, the process of decision-making departs from these principles in practice. Disinvestment decisions are not made nor are decisions weighted against pre-defined criteria. Options appraisal is conducted, but it does not embody the principles of economic evaluation, since options are not considered in terms of their costs and benefits and opportunity cost is not accounted for. There appear to be two reasons why economic evaluation is not used at the local level: (1) the nature of management decisions concerned with the employment of extra staff and new equipment, rather than the choice of medicines or specific interventions usually assessed in published economic evaluation; (2) lack of awareness of the economic evaluation approach to decision-making. These two factors point to a lack of freedom in decision-making at the local level and a lack of understanding of how priority setting can be achieved in practice. CONCLUSION: A more detailed and rigorous approach to prioritisation at the local level is required. Whilst, PCTs have been given greater responsibility for priority setting, they lack the necessary power and understanding of the ways in which long term solutions to problems in health care can be achieved. Economics can be a valuable asset to priority setting and has already filtered into the jargon used by decision makers. Whilst most concepts are understood, the leap to adopting these concepts into the practice of decision-making needs to be made.

A systematic review of the use of economic evaluation in local decision-making.

OBJECTIVES: In view of resource scarcity, decisions have to be made on the optimal allocation of resources and one possible option in health care is economic evaluation. Little is known, however, about the use of economic evaluation. The objectives of this review were to assimilate the empirical evidence on this topic, discuss the main findings, and explore the possible need for further work needed in this area. METHODS: A total of 40 studies were included in the review from a range of countries. A systematic search strategy was used and data from papers were extracted in a systematic way. RESULTS: Pharmacists and clinicians in the US are the most frequently sampled group and postal surveys was the most commonly used method. Despite some positive findings, in most cases there appear to be obstacles to the extensive use of economic evaluation in decision-making. Obstacles can be linked to three factors: (1) institutional and political; (2) cultural; (3) methodological factors associated with economic evaluation itself. CONCLUSION: There has clearly been an increase in the use of economic evaluation over time, especially in the UK, whereas the US appears to have a deep rooted disfavour of the approach. However, there is still little known about the exact influence of economic evaluation at the local level. Whilst work conducted to date has been valuable in providing information about use and barriers to use, further qualitative work is needed to enrich and explain some of the findings from this review.