Reconsidering the scope of cost-effectiveness analyses in healthcare:Views on what and how costs and benefits should be included in economic evaluations of healthcare interventions

This thesis contributed to improvements of methods for the cost-effectiveness analyses (CEA) of healthcare interventions, specifically addressing issues around the inclusion of future costs and benefits, non-medical consumption, and the evaluation of infectious disease surveillance. Through a combination of practical and theoretical research, this research reflected on existing debates and provided new directions for the field.The research started with a critical review of the debate around the inclusion of future costs in CEA. It showed that arguments against the inclusion of future unrelated medical costs generally do not hold and therefore promoted inclusion of these in CEAs and guidelines on how to execute CEAs. The discussion on the inclusion of non-medical consumption costs showed to be less determined, mainly since current outcome measures presumably do not fully and consistently capture benefits related to all benefits beyond health. To be consistent, it has been argued that related costs should therefore be excluded, although others argued that consistency should be achieved by constructing measures that accurately capture all relevant benefits. This thesis further provided an update of PAID (to PAID 3.0), a tool designed to facilitate the inclusion of future costs in CEA by updating estimates of future unrelated medical costs and adding estimates of future non-medical consumption costs. In addition, case studies demonstrated the impact of inclusion and the application thereof. Further, the relevance of differentiating between groups with different risk and disease backgrounds was demonstrated when including future costs. In another chapter, the thesis explored the inclusion of non-health benefits in the value of a Quality-adjusted Life Year (QALY) using Willingness to Pay (WTP) methods, revealing that while many respondents considered non-health benefits when valuing health states, this was minimally reflected in their valuation. This underscored the need for CEA methodologies that consistently and fully capture non-health benefits. It also showed variation of utility of consumption with health status, suggesting (among others) that costs of non-medical consumption should potentially also be adjusted based on health status.Furthermore, the thesis suggested enhancing the framework for the CEA of infectious disease surveillance, emphasizing the need to capture specificities such as uncertainty and the multifaceted impact of surveillance on disease occurrence and treatment. Collectively, this thesis promoted a shift towards more comprehensive economic evaluations of healthcare interventions, urging for future research to build on these foundations to achieve CEAs that more accurately reflect the full scope of the costs and benefits of healthcare interventions.<br/

Session 2-1-B: Gaming Regulators Africa

Goal 1: Eradicate Extreme Poverty Goal 2: Achieve universal primary school education Goal 3: Promote gender equity and empower women Goal 4: Reduce child mortality Goal 5: Stimulate entrepreneurship (SMME; development

Session 2-1-B: A Mandate for Business Leadership: The case of regulated gambling in South Africa

South African agenda - shaped by developmental agenda Comply with global movement on environmental issues Global Economic melt down Political wide spread change – 1994-2013 Strong philosophical orientation i.e. cost/benefit vs. tangible /intangible costs/benefits consumption model (De Vries- 1991) Caution on becoming a gambling dependant nation Purpose to legalise but not aggressive - consumption model (NGB Act 1996 /amended NGB Act 2004) Private enterprise be allowed within tight regulatory framework National lottery- good causes - aggressive –state benefit (NLB Act 2001) Normalisation of society with shift in priorities of the democracy New formulations of Economic black EMPOWERMENT such as BRICS countries with South Africa as part of these emerging economies

Reconsidering the scope of cost-effectiveness analyses in healthcare:Views on what and how costs and benefits should be included in economic evaluations of healthcare interventions

This thesis contributed to improvements of methods for the cost-effectiveness analyses (CEA) of healthcare interventions, specifically addressing issues around the inclusion of future costs and benefits, non-medical consumption, and the evaluation of infectious disease surveillance. Through a combination of practical and theoretical research, this research reflected on existing debates and provided new directions for the field.The research started with a critical review of the debate around the inclusion of future costs in CEA. It showed that arguments against the inclusion of future unrelated medical costs generally do not hold and therefore promoted inclusion of these in CEAs and guidelines on how to execute CEAs. The discussion on the inclusion of non-medical consumption costs showed to be less determined, mainly since current outcome measures presumably do not fully and consistently capture benefits related to all benefits beyond health. To be consistent, it has been argued that related costs should therefore be excluded, although others argued that consistency should be achieved by constructing measures that accurately capture all relevant benefits. This thesis further provided an update of PAID (to PAID 3.0), a tool designed to facilitate the inclusion of future costs in CEA by updating estimates of future unrelated medical costs and adding estimates of future non-medical consumption costs. In addition, case studies demonstrated the impact of inclusion and the application thereof. Further, the relevance of differentiating between groups with different risk and disease backgrounds was demonstrated when including future costs. In another chapter, the thesis explored the inclusion of non-health benefits in the value of a Quality-adjusted Life Year (QALY) using Willingness to Pay (WTP) methods, revealing that while many respondents considered non-health benefits when valuing health states, this was minimally reflected in their valuation. This underscored the need for CEA methodologies that consistently and fully capture non-health benefits. It also showed variation of utility of consumption with health status, suggesting (among others) that costs of non-medical consumption should potentially also be adjusted based on health status.Furthermore, the thesis suggested enhancing the framework for the CEA of infectious disease surveillance, emphasizing the need to capture specificities such as uncertainty and the multifaceted impact of surveillance on disease occurrence and treatment. Collectively, this thesis promoted a shift towards more comprehensive economic evaluations of healthcare interventions, urging for future research to build on these foundations to achieve CEAs that more accurately reflect the full scope of the costs and benefits of healthcare interventions.<br/

An experimental evaluation of the consistency of competitive ability and agonistic dominance in different social contexts in captive bonobos

Bonobos have been described as a relatively egalitarian and female dominant species. The exact nature and quality of their dominance relationships and the existence of female dominance are current topics of dispute. We investigated the consistency across social contexts, the stability in time, and the degree of expression of the competitive feeding ability and agonistic dominance in a captive group of bonobos. First, we examined whether the competitive feeding ranks and agonistic ranks differed in different dyadic contexts, triadic contexts and the whole group context. For some pairs of animals the dominance relationships with respect to competitive feeding altered with different group compositions. The agonistic dominance relationships changed accordingly. The competitive feeding ranks and agonistic ranks in the experiments correlated strongly with each other. The alpha position was occupied by a female, but not all females outranked all males. We suggest that females can profit from each others presence to gain inter-sexual dominance. Second, although the agonistic rank order in the whole group remained the same over at least five years, some dyadic competitive feeding ranks changed over time, resulting in a stronger female intersexual dominance. Third, the degree of expression of the behaviors used to quantify dyadic competitive and agonistic dominance was not high, in line with the popular egalitarian epithet. Notwithstanding its low consistency across contexts, the dominance hierarchy in the whole group has a strong predictive value for other social relationships such as grooming. Given this strong effect of rank on other behaviours and given the strong dependency of rank on social context, the choice of the right party members may be a crucial factor in the fission-fusion processes of free-ranging bonobos

Here be monsters: Investigating sociotechnical interaction in safety-critical work in the maritime domain.

Maritime Pilots and Vessel Traffic Services (VTS) operators work to improve the safety of navigation of seagoing vessels. As in many other safety-critical domains, work is increasingly characterised by the integration and dissemination of information between humans and technology, across disciplines and over multiple geographical locations. Technological advancements such as e-navigation facilitate increased monitoring and control from shore and create new possibilities to provide additional assistance on board vessels. E-navigation has thus a direct impact on navigational assistance as performed by pilots and VTS operators. <br /><br />This thesis views navigational assistance as a case of sociotechnical work in a safety-critical domain. It attempts to understand how work is performed and how it contributes to maritime safety by starting from empirical observation and a Resilience Engineering focus on everyday operations. Interviews, focus groups and field observations on board vessels and in VTS centres were conducted and analysed using an iterative approach, inspired by the principles of grounded theory and the Functional Resonance Analysis Method (FRAM) and informed by the traditions of Workplace Studies, Science and Technology Studies and Activity Theory. A generic FRAM model of navigational assistance was developed to describe the practice of everyday work and how the conditions which affect its performance may vary. A scenario and case study were also analysed and modelled to illustrate how safety may manifest itself in typical and actual events. <br /><br />Successful assistance was found to be dependent on: (i) the use of local knowledge, preparation and foresight to integrate information from a wide range of sources, and; (ii) communication and trust between the pilot, VTS operator, and the master and crew of the vessel, to provide timely assistance to vessels. FRAM was found to be a valuable tool for describing sociotechnical work, but was enriched by borrowing from the work studies traditions, with their strong grounding in empirical observations and themes of 'making work visible', symmetry between human/non-human, and work as activity. This approach indicated that bringing ideas from different traditions together to understand a real work practice may bring us closer to describing 'work as done', and its contribution to safe everyday operations.<br /><br />This thesis concludes that safety is an emergent property of sociotechnical work, which manifests itself through the interaction between humans and other actors in the context in which work is performed. The configuration of a sociotechnical system is not necessarily pre-defined, but is dependent on the human, technological, organisational and natural factors which affect the performance of work. It is inherently uncertain, variable and must adapt to circumstances. In order to inform the design of new systems or evaluate the impact of new technologies, one should therefore take account of the factors which affect how work is normally performed, and also how it is actually performed in specific circumstances to enable safe operations

The pivotal role of rank in grooming and support behaviour in a captive group of bonobos (Pan paniscus)

We investigated dyadic grooming relationships in a captive group of bonobos (Pan paniscus) and questioned what social function grooming fulfils in the market of services and favors. Hereto we examined which of two theoretical models - grooming for support (Seyfarth, 1977, 1980) or grooming according to the similarity principle (de Waal & Luttrell, 1986) - best accounted for the observed grooming distribution. Similarity in traits did not correlate with increased grooming or close proximity among the individuals. Therefore, the similarity hypothesis was rejected. Seyfarths model of rank-related grooming was largely confirmed. The animals distributed their grooming according to the rank of the receivers. We found an exchange between grooming and receipt of support. There was more grooming up than down the hierarchy. However, not all predictions about rank-related competition over grooming were confirmed. We found that dyadic grooming reciprocity indeed increased with decreasing rank distance. Yet, there was no increase of grooming within the dyad with decreasing rank distance and high ranking individuals were not competed over at the highest rates. The observed correlation between grooming and support received represents an important fit with Seyfarths prediction, but does not allow for conclusions about underlying causal processes. Other causal explanations, besides the groom to receive support hypothesis, that could explain a similar correlation are discussed

Durability of treatment effects of the Sleep Position Trainer versus oral appliance therapy in positional OSA: 12-month follow-up of a randomized controlled trial

The Sleep Position Trainer (SPT) is a new option for treating patients with positional obstructive sleep apnea (POSA). This study investigated long-term efficacy, adherence, and quality of life during use of the SPT device compared with oral appliance therapy (OAT) in patients with POSA. This prospective, multicenter trial randomized patients with mild to moderate POSA (apnea-hypopnea index [AHI] 5-30/h) to SPT or OAT. Polysomnography was performed at baseline and after 3 and 12 months' follow-up. The primary endpoint was OSA severity; adherence, quality of life, and adverse events were also assessed. Ninety-nine patients were randomized and 58 completed the study (29 in each group). Median AHI in the SPT group decreased from 13.2/h at baseline to 7.1/h after 12 months (P < 0.001); corresponding values in the OAT group were 13.4/h and 5.0/h (P < 0.001), with no significant between-group difference (P = 1.000). Improvements throughout the study were maintained at 12 months. Long-term median adherence was also similar in the two treatment groups; the proportion of patients who used their device for ≥ 4 h for 5 days in a week was 100% in the SPT group and 97.0% in the OAT group (P = 0.598). The efficacy of SPT therapy was maintained over 12 months and was comparable to that of OAT in patients with mild to moderate POSA. Adherence was relatively high, and similar in the two groups. www.clinicaltrials.gov (NCT02045576

Viral Infections and the Neonatal Brain

This review includes the congenital infections best known by the acronym TORCH (Toxoplasma gondii, rubella virus, cytomegalovirus, and herpes virus), as well as Zika virus infection and perinatally acquired infections (enterovirus, parechovirus, rotavirus, parvovirus). Congenital infections are due to pathogens that can cross the placenta and are more likely to injure the brain when the infection occurs early in pregnancy. There are many similarities, with regards to brain lesions, for congenital Zika syndrome and congenital cytomegalovirus infection. Perinatally acquired viral infections tend to injure the white matter, with cystic evolution being more likely in the (late) preterm infant compared to the full-term infant. Congenital and perinatally acquired viral infections can be associated with adverse neurological outcomes. Prevention is important, especially as therapeutic options are limited. In this review both congenital as well as perinatally acquired viral infections will be discussed with a focus on neuro-imaging findings

The Importance of Measuring SARS-CoV-2-Specific T-Cell Responses in an Ongoing Pandemic

Neutralizing antibodies are considered a correlate of protection against SARS-CoV-2 infection and severe COVID-19, although they are not the only contributing factor to immunity: T-cell responses are considered important in protecting against severe COVID-19 and contributing to the success of vaccination effort. T-cell responses after vaccination largely mirror those of natural infection in magnitude and functional capacity, but not in breadth, as T-cells induced by vaccination exclusively target the surface spike glycoprotein. T-cell responses offer a long-lived line of defense and, unlike humoral responses, largely retain reactivity against the SARS-CoV-2 variants. Given the increasingly recognized role of T-cell responses in protection against severe COVID-19, the circulation of SARS-CoV-2 variants, and the potential implementation of novel vaccines, it becomes imperative to continuously monitor T-cell responses. In addition to “classical” T-cell assays requiring the isolation of peripheral blood mononuclear cells, simple whole-blood-based interferon-γ release assays have a potential role in routine T-cell response monitoring. These assays could be particularly useful for immunocompromised people and other clinically vulnerable populations, where interactions between cellular and humoral immunity are complex. As we continue to live alongside COVID-19, the importance of considering immunity as a whole, incorporating both humoral and cellular responses, is crucial.</p