Applying economic evaluation to public health interventions: The case of interventions to promote physical activity

Copyright @ 2012 The Authors. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.This article has been made available through the Brunel Open Access Publishing Fund.BACKGROUND: This paper explores the application of alternative approaches to economic evaluation of public health interventions, using a worked example of exercise referral schemes (ERSs). METHODS: Cost-utility (CUA) and cost-consequence analyses (CCA) were used to assess the cost-effectiveness of ERSs. For the CUA, evidence was synthesized using a decision analytic model that adopts a lifetime horizon and NHS/Personal Social Services perspective. Outcomes were expressed as incremental cost per quality-adjusted life-year (QALY). CCA was conducted from a partial-societal perspective, including health and non-healthcare costs and benefits. Outcomes were reported in natural units, such as cases of strokes or CHD avoided. RESULTS: Compared with usual care, the incremental cost per QALY of ERS is £20 876. Based on a cohort of 100 000 individuals, CCA estimates cost of ERS at £22 million to the healthcare provider and £12 million to participants. The benefits of ERS include additional 3900 people becoming physically active, 51 cases of CHD avoided, 16 cases of stroke avoided, 86 cases of diabetes avoided and a gain of ∼800 QALYs. CONCLUSIONS: CCA might provide greater transparency than CUA in reporting the outcomes of public health interventions and have greater resonance with stakeholders involved in commissioning these interventions.This work was supported by the NIHR Health Technology Assessment programme (project number 08/72/01). This article is made available through the Brunel Open Access Publishing Fund

Impulse balance and framing effects in threshold public good games

In this paper, we revisit the evidence for framing effects in threshold public good games. Our particular focus is on why the probability of providing the public good appears to be higher in positive, give frames compared with negative, take frames. We show that the impulse balance theory can explain this effect. We also report a new experiment designed to test the predictions of the impulse balance theory. The results of the experiment fit well, both in quantitative and qualitative terms, with our predictions.</p

Late-onset bloodstream infection and perturbed maturation of the gastrointestinal microbiota in premature infants

Late-onset bloodstream infection (LO-BSI) is a common complication of prematurity, and lack of timely diagnosis and treatment can have life-threatening consequences. We sought to identify clinical characteristics and microbial signatures in the gastrointestinal microbiota preceding diagnosis of LO-BSI in premature infants.Daily faecal samples and clinical data were collected over two years from 369 premature neonates (<32 weeks gestation). We analysed samples from 22 neonates who developed LO-BSI and 44 matched control infants. Next-generation sequencing of 16S rRNA gene regions amplified by PCR from total faecal DNA was used to characterise the microbiota of faecal samples preceding diagnosis from infants with LO-BSI and controls. Culture of selected samples was undertaken, and bacterial isolates identified using MALDI-TOF. Antibiograms from bloodstream and faecal isolates were compared to explore strain similarity.From the week prior to diagnosis, infants with LO-BSI had higher proportions of faecal aerobes/facultative anaerobes compared to controls. Risk factors for LO-BSI were identified by multivariate analysis. Enterobacteriaceal sepsis was associated with antecedent multiple lines, low birth weight and a faecal microbiota with prominent Enterobacteriaceae. Staphylococcal sepsis was associated with Staphylococcus OTU faecal over-abundance, and the number of days prior to diagnosis of mechanical ventilation and of the presence of centrally-placed lines. In 12 cases, the antibiogram of the bloodstream isolate matched that of a component of the faecal microbiota in the sample collected closest to diagnosis.The gastrointestinal tract is an important reservoir for LO-BSI organisms, pathogens translocating across the epithelial barrier. LO-BSI is associated with an aberrant microbiota, with abundant staphylococci and Enterobacteriaceae and a failure to mature towards predominance of obligate anaerobes

Understanding Harris' understanding of CEA: is cost effective resource allocation undone?

We summarise and evaluate Harris' criticisms of cost-effectiveness analysis (CEA) and the alternative processes he commends to health care decision makers. In contrast to CEA, Harris' asserts that individuals have a right to life-saving treatment that cannot be denied on the basis of their capacity to benefit. We conclude that, whilst Harris' work has challenged the proponents of CEA and quality-adjusted life years to be explicit about the method's indirect discriminatory characteristics, his arguments ignore important questions about what ‘lives saved’ mean. Harris also attempts to avoid opportunity cost by advocating the same chance of treatment for every person desiring treatment. Using a simple example, we illustrate that an ‘equal chances’ lottery is not in the interest of any patient, as it reduces the chance of treatment for all patients by leaving some of the health budget unspent

In Vitro Antitumour Activity of Some Triorganophosphinegold(I) Thionucleobases

A series of phosphinegold(I) thionucleobase analogues, [R3PAu(SRx)] (R = Et, Ph or chexyl; HSR1 = 2-mercaptobenzoic acid, HSR2 = 2-thiouracil, HSR3 = 6-mercaptopurine and HSR4 = 6-thioguanine) have been examined for their in vitro cytotoxicity in L1210 murine leukemia cells in culture. The range of ID50 values (continuous 48 h exposure) for the complexes is 0.041 - 0.131 μM. The complexes with SR3 and SR3 are generally the most active; however, there is no clear trend associated with the phosphine ligands

Strained alkynes derived from 2,2′-dihydroxy-1,1′-biaryls ; synthesis and copper-free cycloaddition with azides

A series of strained alkynes were prepared from 2,2′-dihydroxy-biaryls. Several were characterised by X-ray crystallography, revealing strained C(sp)–C(sp)–C(sp3) bond angles in the range of 163–167°. Their cycloadditions with azides proceed without a catalyst. Functionalised versions of these reagents have potential applications to materials synthesis and bioconjugations

Pulmonary ORMDL3 is critical for induction of Alternaria -induced allergic airways disease

Genome-wide association studies have identified the ORM (yeast)-like protein isoform 3 (ORMDL3) gene locus on human chromosome 17q to be a highly significant risk factor for childhood-onset asthma. Objective We sought to investigate in vivo the functional role of ORMDL3 in disease inception. Methods An Ormdl3-deficient mouse was generated and the role of ORMDL3 in the generation of allergic airways disease to the fungal aeroallergen Alternaria alternata was determined. An adeno-associated viral vector was also used to reconstitute ORMDL3 expression in airway epithelial cells of Ormdl3 knockout mice. Results Ormdl3 knockout mice were found to be protected from developing allergic airways disease and showed a marked decrease in pathophysiology, including lung function and airway eosinophilia induced by Alternaria. Alternaria is a potent inducer of cellular stress and the unfolded protein response, and ORMDL3 was found to play a critical role in driving the activating transcription factor 6–mediated arm of this response through Xbp1 and downstream activation of the endoplasmic reticulum–associated degradation pathway. In addition, ORMDL3 mediated uric acid release, another marker of cellular stress. In the knockout mice, reconstitution of Ormdl3 transcript levels specifically in the bronchial epithelium resulted in reinstatement of susceptibility to fungal allergen–induced allergic airways disease. Conclusions This study demonstrates that ORMDL3, an asthma susceptibility gene identified by genome-wide association studies, contributes to key pathways that promote changes in airway physiology during allergic immune responses

A Polymorphism Affecting MYB Binding within the Promoter of the PDCD4 Gene is Associated with Severe Asthma in Children

A previous genome-wide association study in asthma revealed putative associations that merit further investigation. In this study, the genome-wide significant associations of SNPs at the 5% false discovery rate were examined in independent groups of severe asthmatics. The panel consisted of 397 severe asthmatic adults, 116 severe asthmatic children, and a collection of 207 family-trios with an asthmatic proband. Three SNPs in the PDCD4 gene (rs6585018:G>A, rs1322997:C>A, and rs34104444:G>A) were significantly associated with severe childhood asthma (P values: 0.003, 0.002, 0.004) and total immunoglobulin E (IgE) levels (P values: 0.034, 0.041, 0.052). In an independent group of 234 asthmatic children and 652 controls, PDCD4 SNPs rs1407696:T>G and rs11195360:T>C were associated with total IgE levels (P values: 0.006, 0.014). In silico analysis of PDCD4 locus showed that rs6585018:G>A had the potential to affect MYB transcription factor binding, shown to act as a PDCD4-transcription inducer. Electromobility shift assays and reporter assays revealed that rs6585018:G>A alters MYB binding thereby influencing the expression of PDCD4. SNPs within MYB itself confer susceptibility to eosinophilia and asthma. Our association between a variant MYB binding site in PDCD4 and the severest form of childhood asthma therefore suggests that PDCD4 is a novel molecule of importance to asthmatic inflammatory responses