Balancing equity and efficiency in the Dutch basic benefits package using the principle of proportional shortfall

Economic evaluations are increasingly used to inform decisions regarding the allocation of scarce health care resources. To systematically incorporate societal preferences into these evaluations, quality-adjusted life year gains could be weighted according to some equity principle, the most suitable of which is a matter of frequent debate. While many countries still struggle with equity concerns for priority setting in health care, the Netherlands has reached a broad consensus to use the concept of proportional shortfall. Our study evaluates the concept and its support in the Dutch health care context. We discuss arguments in the Netherlands for using proportional shortfall and difficulties in transitioning from principle to practice. In doing so, we address universal issues leading to a systematic consideration of equity concerns for priority setting in health care. The article thus has relevance to all countries struggling with the formalization of equity concerns for priority setting

Therapies with CCL25 require controlled release via microparticles to avoid strong inflammatory reactions

Background: Chemokine therapy with C-C motif chemokine ligand 25 (CCL25) is currently under investigation as a promising approach to treat articular cartilage degeneration. We developed a delayed release mechanism based on Poly (lactic-co-glycolic acid) (PLGA) microparticle encapsulation for intraarticular injections to ensure prolonged release of therapeutic dosages. However, CCL25 plays an important role in immune cell regulation and inflammatory processes like T-cell homing and chronic tissue inflammation. Therefore, the potential of CCL25 to activate immune cells must be assessed more thoroughly before further translation into clinical practice. The aim of this study was to evaluate the reaction of different immune cell subsets upon stimulation with different dosages of CCL25 in comparison to CCL25 released from PLGA particles. Results: Immune cell subsets were treated for up to 5 days with CCL25 and subsequently analyzed regarding their cytokine secretion, surface marker expression, polarization, and migratory behavior. The CCL25 receptor C-C chemokine receptor type 9 (CCR9) was expressed to a different extent on all immune cell subsets. Direct stimulation of peripheral blood mononuclear cells (PBMCs) with high dosages of CCL25 resulted in strong increases in the secretion of monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), interleukin-1 beta (IL-1 beta), tumor-necrosis-factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), upregulation of human leukocyte antigen-DR (HLA-DR) on monocytes and CD4(+) T-cells, as well as immune cell migration along a CCL25 gradient. Immune cell stimulation with the supernatants from CCL25 loaded PLGA microparticles caused moderate increases in MCP-1, IL-8, and IL-1 beta levels, but no changes in surface marker expression or migration. Both CCL25-loaded and unloaded PLGA microparticles induced an increase in IL-8 and MCP-1 release in PBMCs and macrophages, and a slight shift of the surface marker profile towards the direction of M2-macrophage polarization. Conclusions: While supernatants of CCL25 loaded PLGA microparticles did not provoke strong inflammatory reactions, direct stimulation with CCL25 shows the critical potential to induce global inflammatory activation of human leukocytes at certain concentrations. These findings underline the importance of a safe and reliable release system in a therapeutic setup. Failure of the delivery system could result in strong local and systemic inflammatory reactions that could potentially negate the benefits of chemokine therapy

Health Seeking Behaviour and Utilization of Health Facilities for Schistosomiasis-Related Symptoms in Ghana

The World Health Organization recommends that long-term benefit of schistosomiasis control should include treatment in local health facilities. This means that patients should visit a hospital or clinic with their complaints. However, little is known about whether they do so. We conducted a study in three regions of Ghana and interviewed two thousand people about whether they recently had schistosomiasis-related symptoms such as blood in urine or blood in faeces, and what they had done about it. We included fever (mostly caused by malaria) for comparison. We found that 40% of patients with urinary symptoms sought care compared to 70% of those with intestinal symptoms and 90% with fever. Overall, only 20% of all schistosomiasis-related symptoms were reported to a hospital or clinic, compared to 30% for fever. Self-medication with allopathic (i.e., orthodox) medicines was the main alternative. Our study showed that the most important determinant for seeking health care or visiting a health facility is perceived severity of the symptom. Factors such as age, sex, socio-economic status and geographic region showed no impact or a clear pattern. We conclude that many schistosomiasis patients do not visit a health facility, the only place with effective drugs, necessitating additional control measures

The effects of lead time and visual aids in TTO valuation: a study of the EQ-VT framework

__Abstract__ __Background__ The effect of lead time in time trade-off (TTO) valuation is not well understood. The purpose of this study was to investigate the effects on health-state valuation of the length of lead time and the way the lead-time TTO task is displayed visually. __Methods__ Using two general population samples, we compared three lead-time TTO variants: 10 years of lead time in full health preceding 5 years of unhealthy time (standard); 5 years of lead time preceding 5 years of unhealthy time (experimental); and 10 years of lead time and 5 years of unhealthy time, presented with a visual aid to highlight the point where the lead time ends (experimental). Participants were randomized to receive one of the lead-time variants, as administered by a computer software program. __Results__ Health-state values generated by TTO valuation tasks using a longer lead time were slightly lower than those generated by tasks using a shorter lead time. When lead time and unhealthy time were presented with visual aids highlighting the difference between the lead time and unhealthy time, respondents spent more time considering health states with a value close to 0. __Conclusions__ Different lead-time time trade-off variants should be carefully studied in order to achieve the best measurement of health-state values using this new method

Finite element analysis of the effect of cementing concepts on implant stability and cement fatigue failure

Background and purpose Two contradictory cementing techniques (using an undersized stem versus a canal-filling stem) can both lead to excellent survival rates, a phenomenon known as the “French paradox”. Furthermore, previous studies have indicated that the type of bone supporting the cement mantle may affect implant survival. To further evaluate the mechanical consequences of variations in cementing technique, we studied the effect of implant size and type of bone supporting the cement mantle on the mechanical performance of cemented total hip arthroplasty, using finite element analysis

Valuing EQ-5D-Y: the current state of play

Background For nearly a decade, value sets for the EQ-5D-Y were not available, reflecting challenges in valuing child HRQoL. A methodological research programme led to publication of a valuation protocol in 2020, which was rapidly taken up by local study teams. By the end of 2022, between 11 and 17 EQ-5D-Y value sets will be available, more than for any other child HRQoL measure. It is timely to review the experience of those using the protocol to identify early learnings and remaining issues where more research is needed. Methods In June 2021, the EuroQol Group organised a three-day workshop, bringing together all those involved in EQ-5D-Y value set studies and related methodological research concerning EQ-5D-Y and valuation. Workshop discussions were captured by note taking and recording all sessions and online chat. A narrative summary of all sessions was produced and synthesised to identify points of agreement and aspects of methods where uncertainty remains. Results There was broad agreement that DCE is working well as the principal valuation method. However, the most appropriate means of anchoring the latent scale values produced by DCE remains unclear. Some studies have deviated from the protocol by extending the number of states included in TTO tasks, to better support modelling of DCE and TTO. There is ongoing discussion about the relative merits of alternative variants of TTO and other methods for anchoring. Very few studies have consulted with local end-users to gauge the acceptability of methods used to value EQ-5D-Y. Conclusions Priority areas for research include testing alternative methods for anchoring DCE data; exploring the preferences of adolescents; and scale differences in values for EQ-5D-Y and adult EQ-5D states, and implications of such differences for the use of EQ-5D-Y values in HTA. Given the normative elements of the protocol, engaging with HTA bodies and other local users should be the first step for all future value set studies. Value sets undertaken to date are for the three-level EQ-5D-Y. However, the issues discussed in this paper are equally relevant to valuation of the five-level version of EQ-5D-Y; indeed, similar challenges are encountered valuing any measure of child HRQoL

Mathematical modelling of lymphatic filariasis elimination programmes in India: Required duration of mass drug administration and post-treatment level of infection indicators

Background: India has made great progress towards the elimination of lymphatic filariasis. By 2015, most endemic districts had completed at least five annual rounds of mass drug administration (MDA). The next challenge is to determine when MDA can be stopped. We performed a simulation study with the individual-based model LYMFASIM to help clarify this. Methods: We used a model-variant for Indian settings. We considered different hypotheses on detectability of antigenaemia (Ag) in relation to underlying adult worm burden, choosing the most likely hypothesis by comparing the model predicted association between community-level microfilaraemia (Mf) and antigenaemia (Ag) prevalence levels to observed data (collated from literature). Next, we estimated how long MDA must be continued in order to achieve elimination in different transmission settings and what Mf and Ag prevalence may still remain 1 year after the last required MDA round. The robustness of key-outcomes was assessed in a sensitivity analysis. Results: Our model matched observed data qualitatively well when we assumed an Ag detection rate of 50 % for single worm infections, which increases with the number of adult worms (modelled by relating detection to the presence of female worms). The required duration of annual MDA increased with higher baseline endemicity and lower coverage (varying between 2 and 12 rounds), while the remaining residual infection 1 year after the last required treatment declined with transmission intensity. For low and high transmission settings, the median residual infection levels were 1.0 % and 0.4 % (Mf prevalence in the 5+ population), and 3.5 % and 2.0 % (Ag prevalence in 6-7 year-old children). Conclusion: To achieve elimination in high transmission settings, MDA must be continued longer and infection levels must be reduced to lower levels than in low-endemic communities. Although our simulations were for Indian settings, qualitatively similar patterns are also expected in other areas. This should be taken into account in decision algorithms to define whether MDA can be interrupted. Transmission assessment surveys should ideally be targeted to communities with the highest pre-control transmission levels, to minimize the risk of programme failure