Pitfalls in the application of utility functions to the valuation of human life

AbstractSafety strategies in the process and other industries depend ultimately on how much the owners and operators decide should be spent on protection systems to protect workers and the public from potential plant hazards. An important input to decisions of this sort is the value of life, which needs to be assessed in a valid manner so that safety decisions can be made properly. A key reference point for decisions on safety investment decisions in the UK is a 1999 study on the “value of a prevented fatality” (VPF), which employs a two-injury chained model that has been shown previously by the present authors to possess internal inconsistencies. The 1999 study made extensive use of utility functions to interpret survey data, and it is this feature that is explored in this paper. It will be explained here how different forms of utility function of the Exponential family can produce the same figure for an intermediate parameter in the calculation of the VPF from the two-injury chained model. Exponential utility functions are, however, unlikely to provide a realistic representation if their calculated risk-aversions need to be negative or zero in order to match survey data, which would imply an incautious attitude amongst those taking decisions on safety. The use of an incompletely specified wealth threshold in the utility modelling is explored in the light of a proposal by the authors of the 1999 study that a second utility function can be used to determine the individual's utility when his wealth lies below the threshold, which constitutes the lower limit of validity of the first utility function. The proposition is shown to be untenable. The results presented in this paper raise further concerns about the lack of validity of the 1999 study on which the UK VPF is based and hence on the safety decisions that have been made in consequence

Emergent approaches to the meta-analysis of multiple heterogeneous complex interventions.

BACKGROUND: Multiple interventions meta-analysis has been recommended in the methodological literature as a tool for evidence synthesis when a heterogeneous set of interventions is included in the same review—and, more recently, when a heterogeneous set of complex interventions is included. However, there is little guidance on the use of this method with complex interventions. This article suggests two approaches to model complexity and heterogeneity through this method. DISCUSSION: 'Clinically meaningful units' groups interventions by modality or similar theory of change, whereas 'components and dismantling' separates out interventions into combinations of components and either groups interventions by the combination of components they demonstrate or extracts effects for each identified component and, possibly, interactions between components. Future work in systematic review methodology should aim to understand how to develop taxonomies of components or theories of change that are internally relevant to the studies in these multiple interventions meta-analyses. SUMMARY: Despite little meaningful prior guidance to its use in this context, multiple interventions meta-analysis has the potential to be a useful tool for synthesising heterogeneous sets of complex interventions. Researchers should choose an approach in accordance with their specific aims in their systematic review

The entomopathogenic fungus Beauveria bassiana reduces instantaneous blood feeding in wild multi-insecticide-resistant Culex quinquefasciatus mosquitoes in Benin, West Africa.

BACKGROUND: Mosquito-borne diseases are still a major health risk in many developing countries, and the emergence of multi-insecticide-resistant mosquitoes is threatening the future of vector control. Therefore, new tools that can manage resistant mosquitoes are required. Laboratory studies show that entomopathogenic fungi can kill insecticide-resistant malaria vectors but this needs to be verified in the field. METHODS: The present study investigated whether these fungi will be effective at infecting, killing and/or modifying the behaviour of wild multi-insecticide-resistant West African mosquitoes. The entomopathogenic fungi Metarhizium anisopliae and Beauveria bassiana were separately applied to white polyester window netting and used in combination with either a permethrin-treated or untreated bednet in an experimental hut trial. Untreated nets were used because we wanted to test the effect of fungus alone and in combination with an insecticide to examine any potential additive or synergistic effects. RESULTS: In total, 1125 female mosquitoes were collected during the hut trial, mainly Culex quinquefasciatus Say. Unfortunately, not enough wild Anopheles gambiae Giles were collected to allow the effect the fungi may have on this malaria vector to be analysed. None of the treatment combinations caused significantly increased mortality of Cx. quinquefasciatus when compared to the control hut. The only significant behaviour modification found was a reduction in blood feeding by Cx. quinquefasciatus, caused by the permethrin and B. bassiana treatments, although no additive effect was seen in the B. bassiana and permethrin combination treatment. Beauveria bassiana did not repel blood foraging mosquitoes either in the laboratory or field. CONCLUSIONS: This is the first time that an entomopathogenic fungus has been shown to reduce blood feeding of wild mosquitoes. This behaviour modification indicates that B. bassiana could potentially be a new mosquito control tool effective at reducing disease transmission, although further field work in areas with filariasis transmission should be carried out to verify this. In addition, work targeting malaria vector mosquitoes should be carried out to see if these mosquitoes manifest the same behaviour modification after infection with B. bassiana conidia

Lifestyle weight management programmes for children: A systematic review using Qualitative Comparative Analysis to identify critical pathways to effectiveness.

This study aimed to identify critical features of successful lifestyle weight management interventions for overweight children (0-11years). Eleven qualitative UK-based studies examining children's, parents' and providers' perspectives and experiences of programmes were synthesised to identify components felt to be critical. Studies for this views synthesis were identified from existing reviews and an update of one review's search, which was run in December 2015. The identified components were then explored in a synthesis of intervention evaluations (five 'most effective' and 15 'least effective') conducted in western Europe, North America, Australia or New Zealand. The intervention evaluations were identified from existing reviews and an update of one review's search, which was run in March 2016. This evaluation synthesis was carried out using Qualitative Comparative Analysis. Three important mechanisms were present in all the most effective interventions but absent in all the least effective: 1/ showing families how to change: a) providing child physical activity sessions, b) delivering practical behaviour change strategy sessions, c) providing calorie intake advice; 2/ ensuring all the family are on board: a) delivering discussion/education sessions for both children and parents, b) delivering child-friendly sessions, c) aiming to change behaviours across the whole family; 3/ enabling social support for both parents and children by delivering both child group sessions and parent group sessions. To conclude, programmes should ensure the whole family is on board the programme, that parents and children can receive social support and are not just told what to change, but shown how

Investigating the causes of patient anxiety at induction of anaesthesia: A mixed methods study

Aim: To investigate patient anxiety at anaesthetic induction and whether this is affected by anaesthetic room interventions. Methods: A mixed methods study was carried out: pre-induction interventions were directly observed. Patient anxiety was assessed quantitatively with cardiovascular changes, the visual analogue scale and the state-trait anxiety inventory. Interviews allowed qualitative assessment. Results: Patient-reported anxiety did not correlate with cardiovascular changes. Anaesthetic room interventions were not predictive of anxiety. Postoperative interviews identified five sources of anxiety, mostly related to preparation for surgery. Staff responses to anxiety were also highlighted. Discussion: Patient-reported anxiety and its biological response are not correlated. Pre-induction interventions do not contribute to anxiety. Anxiety levels at induction are similar to or lower than earlier in the preoperative period. Conclusions: On induction of anaesthesia, patients have little control over their situation but are actively reassured and distracted by theatre staff. Our data suggest staff are good at this. More could still be done to reduce preoperative sources of anxiety

Integration of academic and health education for the prevention of physical aggression and violence in young people: systematic review, narrative synthesis and intervention components analysis.

OBJECTIVES: To systematically review evidence on the effectiveness of interventions including integration of academic and health education for reducing physical aggression and violence, and describe the content of these interventions. DATA SOURCES: Between November and December 2015, we searched 19 databases and 32 websites and consulted key experts in the field. We updated our search in February 2018. ELIGIBILITY CRITERIA: We included randomised trials of school-based interventions integrating academic and health education in students aged 4-18 and not targeted at health-related subpopulations (eg, learning or developmental difficulties). We included evaluations reporting a measure of interpersonal violence or aggression. DATA EXTRACTION AND ANALYSIS: Data were extracted independently in duplicate, interventions were analysed to understand similarities and differences and outcomes were narratively synthesised by key stage (KS). RESULTS: We included 13 evaluations of 10 interventions reported in 20 papers. Interventions included either full or partial integration, incorporated a variety of domains beyond the classroom, and used literature, local development or linking of study skills and health promoting skills. Evidence was concentrated in KS2, with few evaluations in KS3 or KS4, and evaluations had few consistent effects; evaluations in KS3 and KS4 did not suggest effectiveness. DISCUSSION: Integration of academic and health education may be a promising approach, but more evidence is needed. Future research should consider the 'lifecourse' aspects of these interventions; that is, do they have a longitudinal effect? Evaluations did not shed light on the value of different approaches to integration

Cellular Inhibitor of Apoptosis (cIAP)-mediated ubiquitination of Phosphofurin Acidic Cluster Sorting protein 2 (PACS-2) negatively regulates Tumor necrosis factor-Related Apoptosis-Inducing Ligand (TRAIL) cytotoxicity

Lysosomal membrane permeabilization is an essential step in TRAIL-induced apoptosis of liver cancer cell lines. TRAIL-induced lysosomal membrane permeabilization is mediated by the multifunctional sorting protein PACS-2 and repressed by the E3 ligases cIAP-1 and cIAP-2. Despite the opposing roles for PACS-2 and cIAPs in TRAIL-induced apoptosis, an interaction between these proteins has yet to be examined. Herein, we report that cIAP-1 and cIAP-2 confer TRAIL resistance to hepatobiliary cancer cell lines by reducing PACS-2 levels. Under basal conditions, PACS-2 underwent K48-linked polyubiquitination, resulting in PACS-2 proteasomal degradation. Biochemical assays showed cIAP-1 and cIAP-2 interacted with PACS-2 in vitro and co-immunoprecipitation studies demonstrated that the two cIAPs bound PACS-2 in vivo. More importantly, both cIAP-1 and cIAP-2 directly mediated PACS-2 ubiquitination in a cell-free assay. Single c-Iap-1 or c-Iap-2 gene knock-outs in mouse hepatocytes did not lead to PACS-2 accumulation. However, deletion of both cIAP-1 and cIAP-2 reduced PACS-2 ubiquitination, which increased PACS-2 levels and sensitized HuH-7 cells to TRAIL-induced lysosomal membrane permeabilization and apoptosis. Correspondingly, deletion of cIAPs sensitized wild-type, but not PACS-2-deficient hepatocarcinoma cells or Pacs-2-/- mouse hepatocytes to TRAIL-induced apoptosis. Together, these data suggest cIAPs constitutively downregulate PACS-2 by polyubiquitination and proteasomal degradation, thereby restraining TRAIL-induced killing of liver cancer cells. © 2014 Guicciardi et al

The importance of service-users' perspectives: A systematic review of qualitative evidence reveals overlooked critical features of weight management programmes.

BACKGROUND: Extensive research effort shows that weight management programmes (WMPs) targeting both diet and exercise are broadly effective. However, the critical features of WMPs remain unclear. OBJECTIVE: To develop a deeper understanding of WMPs critical features, we undertook a systematic review of qualitative evidence. We sought to understand from a service-user perspective how programmes are experienced, and may be effective, on the ground. SEARCH STRATEGY: We identified qualitative studies from existing reviews and updated the searches of one review. INCLUSION CRITERIA: We included UK studies capturing the views of adult WMP users. DATA EXTRACTION AND SYNTHESIS: Thematic analysis was used inductively to code and synthesize the evidence. MAIN RESULTS: Service users were emphatic that supportive relationships, with service providers or WMP peers, are the most critical aspect of WMPs. Supportive relationships were described as providing an extrinsic motivator or "hook" which helped to overcome barriers such as scepticism about dietary advice or a lack confidence to engage in physical activity. DISCUSSION AND CONCLUSIONS: The evidence revealed that service-users' understandings of the critical features of WMPs differ from the focus of health promotion guidance or descriptions of evaluated programmes which largely emphasize educational or goal setting aspects of WMPs. Existing programme guidance may not therefore fully address the needs of service users. The study illustrates that the perspectives of service users can reveal unanticipated intervention mechanisms or underemphasized critical features and underscores the value of a holistic understanding about "what happens" in complex psychosocial interventions such as WMPs

Interpretive analysis of 85 systematic reviews suggests narrative syntheses and meta-analyses are incommensurate in argumentation

Introduction. Using Toulmin’s argumentation theory, we analysed the texts of systematic reviews in the area of workplace health promotion to explore differences in the modes of reasoning embedded in reports of narrative synthesis as compared to reports of meta-analysis. Methods. We used framework synthesis, grounded theory and cross-case analysis methods to analyse 85 systematic reviews addressing intervention effectiveness in workplace health promotion. Results. Two core categories, or ‘modes of reasoning’, emerged to frame the contrast between narrative synthesis and meta-analysis: practical-configurational reasoning in narrative synthesis (‘what is going on here? what picture emerges?’) and inferential-predictive reasoning in meta-analysis (‘does it work, and how well? will it work again?’). Modes of reasoning examined quality and consistency of the included evidence differently. Meta-analyses clearly distinguished between warrant and claim, whereas narrative syntheses often presented joint warrant-claims. Conclusion. Narrative syntheses and meta-analyses represent different modes of reasoning. Systematic reviewers are likely to be addressing research questions in different ways with each method. It is important to consider narrative synthesis in its own right as a method and to develop specific quality criteria and understandings of how it is done, not merely as a complement to, or second-best option for, meta-analysis