Cost-effectiveness of insulin detemir compared with NPH insulin in people with type 2 diabetes in Denmark, Finland, Norway, and Sweden.

Abstract Objective: To assess the cost-effectiveness of insulin detemir compared with Neutral Protamine Hagedorn (NPH) insulin when initiating insulin treatment in people with type 2 diabetes mellitus (T2DM) in Denmark, Finland, Norway, and Sweden. Methods: Efficacy and safety data were derived from a 20-week multi-centre randomized controlled head-to-head clinical trial comparing insulin detemir and NPH insulin in insulin naïve people with T2DM, and short-term (1-year) cost effectiveness analyses were performed. As no significant differences in HbA(1c) were observed between the two treatment arms, the model was based on significant differences in favour of insulin detemir in frequency of hypoglycaemia (Rate-Ratio = 0.52; CI = 0.44-0.61) and weight gain (Δ = 0.9 kg). Model outcomes were measured in Quality Adjusted Life Years (QALYs) using published utility estimates. Acquisition costs for insulin and direct healthcare costs associated with non-severe hypoglycaemic events were obtained from National Health Service public sources. One-way and probabilistic sensitivity analyses were performed. Results: Based on lower incidence of non-severe hypoglycaemic events and less weight gain, the QALY gain from initiating treatment with insulin detemir compared with NPH insulin was 0.01 per patient per year. Incremental cost-effectiveness ratios for the individual countries were: Denmark, Danish Kroner 170,852 (€22,933); Finland, €28,349; Norway, Norwegian Kroner 169,789 (€21,768); and Sweden, Swedish Krona 226,622 (€25,097) per QALY gained. Possible limitations of the study are that data on hypoglycaemia and relative weight benefits from a clinical trial were combined with hypoglycaemia incidence data from observational studies. These populations may have slightly different patient characteristics. Conclusions: The lower risk of non-severe hypoglycaemia and less weight gain associated with using insulin detemir compared with NPH insulin when initiating insulin treatment in insulin naïve patients with type 2 diabetes provide economic benefits in the short-term. Based on cost/QALY threshold values, this represents good value for money in the Nordic countries. Using a short-term modelling approach may be conservative, as reduced frequency of hypoglycaemia and less weight gain may also have positive long-term health-related implications

Nonselective versus Selective Inhibition of Inducible Nitric Oxide Synthase in Experimental Endotoxic Shock

The effects of two nitric oxide synthase (NOS) inhibitors with different isoform selectivity were compared in a murine model of endotoxemia. Mice challenged with 70 mg/kg intraperitoneal (ip) lipopolysaccharide (LPS) were treated 6 h after LPS with either NG-γ-L-arginine methyl ester (LNAME, nonselective NOS inhibitor, 10-60 mg/kg), L-canavanine (selective inhibitor of inducible NOS, 50-300 mg/kg), or saline (0.2 mL) given ip. In a subset of mice, plasma concentrations of nitrate (NO breakdown product), lipase (pancreas injury), lactate dehydrogenase, and transaminases (liver injury) were measured 16 h after LPS. Although both inhibitors reduced plasma nitrate, they produced contrasting effects on survival and organ injury. L-NAME enhanced liver damage and tended to accelerate the time of death, while L-canavanine significantly reduced mortality and had no deleterious effects in terms of organ damage. These results indicate that nonselective NOS inhibitors are detrimental in endotoxic shock and support the potential usefulness of selective inducible NOS inhibitors in this settin

Editorial: Immunological challenges around pregnancy complications associated with failures of maternal tolerance to the fetus

Obstetric

Connected Hearing Devices and Audiologists: The User-Centered Development of Digital Service Innovations

Today, medical technology manufacturers enter the service market through the development of digital service innovations. In the field of audiology, these developments increasingly shift the service capacities from audiologists to manufacturers and technical systems. However, the technology-driven developments of manufacturers lack acceptance of hearing device users and undermine the important role of audiologists within the service provision. By following a user-centered design approach in order to deal with the technological and social challenges of disruptive services, we aim to develop service innovations on an integrated service platform in the field of tele-audiology. To ensure the acceptance of technology-driven service innovations among hearing device users and audiologists, we systematically integrated these actors in a participatory innovation process. With qualitative and quantitative data we identified several requirements and preferences for different service innovations in the field of tele-audiology. According to the preferences of the different actors, we proposed a service platform approach based on a connected hearing device in three pillars of application: 1) one-to-one (1:1) service innovations based on a remote fitting concept directly improve the availability of services offered by audiologists without being physically present. Based on this, 2) one-to-many (1:N) service innovations allow the use of the connected hearing device as an indirect data source for training a machine learning algorithm that empowers users through the automation of service processes. A centralized server system collects the data and performs the training of this algorithm. As a future outlook, we show potentials to use the connected hearing device for 3) cross-industry (N:M) service innovations in contexts outside the healthcare domain and give practical implications for the market launch of successful service innovations in the field of tele-audiology

How do people with experience of infertility value different aspects of assistive reproductive therapy? Results from a multi-country discrete choice experiment

Objectives: Assistive reproductive therapies can help those who have difficulty conceiving but different forms of assistive reproductive therapies are associated with different treatment characteristics. We undertook a large, multinational discrete choice experiment to understand patient preferences for assistive reproductive therapies. Methods: We administered an online discrete choice experiment with persons who had experience with subfertility or assistive reproductive therapies in the USA, UK, the Nordic region (Denmark, Norway, Sweden, Finland), Spain, and China. Attributes encouraged trade-offs between effectiveness, risk of adverse effects, treatment (dis)comfort, (in)convenience, cost per cycle and shared decision making. We used multinomial logit and mixed-logit models to estimate preferences and attribute importance by country/region, and estimated willingness to pay for changes in attribute levels. Results: A total of 7565 respondents participated. Mixed logit had a better fit than multinomial logit across all samples. Preferences moved in expected directions across all samples, but the relative importance of attributes differed between countries. Willingness to pay was greatest for improvements in effectiveness and a greater degree of shared decision making, and we observe a substantial ‘option value’ independent of treatment characteristics. Unexpectedly, preferences over cost were insignificant in the Chinese sample, limiting the use of willingness to pay in this sample. Conclusions: Respondents balanced concerns for effectiveness with other considerations, including the cost and (dis)comfort of treatment, and the degree of shared decision making, but there is also substantial option value independent of treatment characteristics, demonstrating value of assistive reproductive therapies to individuals with experience of subfertility. We hypothesise that price insensitivity in the Chinese sample may reflect a degree of social desirability bias

Is the public supportive and willing to pay for a national assistive reproductive therapies programme? Results from a multicountry survey

Objectives: To understand attitudes towards infertility and willingness to pay (WTP) towards a publicly funded national assistive reproductive therapies (ART) programme. Design: Attitudes survey with dichotomous and open-ended WTP questions. Setting: Online survey administered in the USA, UK, Norway, Sweden, Finland, Denmark and China. Participants: 7945 respondents, analysed by country. Nordic respondents were pooled into a regionally representative sample. Primary and secondary outcome measures: Primary outcome measures were proportion of sample agreeing with different infertility-related and ART-related value statements and supporting a monthly contribution to fund a national ART programme, expressed in local currency. Secondary outcome measure was maximum WTP. Results: Across the nationally representative samples, 75.5% of all respondents agreed with infertility as a medical condition and 82.3% and 83.7% with ART eligibility for anyone who has difficulty having a baby or a medical problem preventing them from having a baby, respectively. 56.4% of respondents supported a defined monthly contribution and 73.9% supported at least some additional contribution to fund a national ART programme. Overall, converting to euros, median maximum WTP was €3.00 and mean was €15.47 (95% CI 14.23 to 16.72) per month. Maximum WTP was highest in China and the USA and lowest in the European samples. Conclusions: This large, multicountry survey extends our understanding of public attitudes towards infertility and fertility treatment beyond Europe. It finds evidence that a majority of the public in all sampled countries/regions views infertility as a treatable medical condition and supports the idea that all infertile individuals should have access to treatments that improve the chance of conception. There was also strong agreement with the idea that the desire for children is a basic human need. WTP questions showed that a majority of respondents supported a monthly contribution to fund a national ART programme, although there is some evidence of an acquiescence bias that may overstate support among specific samples

Anaerobic sulfur oxidation underlies adaptation of a chemosynthetic symbiont to oxic-anoxic interfaces

Chemosynthetic symbioses occur worldwide in marine habitats, but comprehensive physiological studies of chemoautotrophic bacteria thriving on animals are scarce. Stilbonematinae are coated by thiotrophic Gammaproteobacteria. As these nematodes migrate through the redox zone, their ectosymbionts experience varying oxygen concentrations. However, nothing is known about how these variations affect their physiology. Here, by applying omics, Raman microspectroscopy, and stable isotope labeling, we investigated the effect of oxygen on “Candidatus Thiosymbion oneisti.” Unexpectedly, sulfur oxidation genes were upregulated in anoxic relative to oxic conditions, but carbon fixation genes and incorporation of (13)C-labeled bicarbonate were not. Instead, several genes involved in carbon fixation were upregulated under oxic conditions, together with genes involved in organic carbon assimilation, polyhydroxyalkanoate (PHA) biosynthesis, nitrogen fixation, and urea utilization. Furthermore, in the presence of oxygen, stress-related genes were upregulated together with vitamin biosynthesis genes likely necessary to withstand oxidative stress, and the symbiont appeared to proliferate less. Based on its physiological response to oxygen, we propose that “Ca. T. oneisti” may exploit anaerobic sulfur oxidation coupled to denitrification to proliferate in anoxic sand. However, the ectosymbiont would still profit from the oxygen available in superficial sand, as the energy-efficient aerobic respiration would facilitate carbon and nitrogen assimilation. IMPORTANCE Chemoautotrophic endosymbionts are famous for exploiting sulfur oxidization to feed marine organisms with fixed carbon. However, the physiology of thiotrophic bacteria thriving on the surface of animals (ectosymbionts) is less understood. One longstanding hypothesis posits that attachment to animals that migrate between reduced and oxic environments would boost sulfur oxidation, as the ectosymbionts would alternatively access sulfide and oxygen, the most favorable electron acceptor. Here, we investigated the effect of oxygen on the physiology of “Candidatus Thiosymbion oneisti,” a gammaproteobacterium which lives attached to marine nematodes inhabiting shallow-water sand. Surprisingly, sulfur oxidation genes were upregulated under anoxic relative to oxic conditions. Furthermore, under anoxia, the ectosymbiont appeared to be less stressed and to proliferate more. We propose that animal-mediated access to oxygen, rather than enhancing sulfur oxidation, would facilitate assimilation of carbon and nitrogen by the ectosymbiont

A marine bacterial enzymatic cascade degrades the algal polysaccharide ulvan

International audienc

Tailored support may be required to reduce the impact of the infertility journey on mental health, relationships and daily lives of infertile patients and partners to infertile patients

Research question What is the psychological impact of infertility on infertile patients and partners of infertile patients? Design This online, international, quantitative survey assessed the impact of infertility on mental health, relationships and daily activities for 1944 respondents. Respondents were male or female infertile patients (n = 1037) or partners to infertile patients (n = 907; not necessarily partners of the patient sample) and were recruited at different stages of the treatment journey. Results The most common emotions were ‘sadness’ at infertility diagnosis and ‘anxiety’ during treatment. Emotions differed in nature and intensity throughout the journey. Envy of others who achieved pregnancy was frequently reported by women. More than half of respondents (60.4%; n = 1174) perceived the infertility journey to have impacted their mental health, and 44.1% (n = 857) of respondents sought mental health support. More patients reported mental health impacts (70.1%, n = 727) than partners (49.3%, n = 447). One in three respondents indicated that their relationship had suffered due to the infertility diagnosis. Of these respondents, 55.0% (n = 409) strongly agreed that infertility caused an emotional strain. Patients more often than partners reported a detrimental impact on daily activities. Respondents most commonly agreed with statements regarding an ‘effect on work–life balance’. Conclusion Treatment journey stages are defined by their impact profile, which differs between infertile patients and partners of infertile patients. Negative impacts are diverse (mental health, relational, daily activities). There was disparity between the number of respondents reporting mental health issues and the number seeking mental health support. This indicates the need for support services tailored to different treatment stages

t8code - scalable and modular adaptive mesh refinement

t8code is a versatile open source library for parallel adaptive mesh refinement on hybrid meshes. [1] It is exascale-ready and capable of efficiently managing meshes with up to a trillion elements distributed on a million of cores as already shown in a peer-reviewed research paper. [2] On the top-level, t8code uses forests of trees to represent unstructured meshes with complex geometries. Space-filling curves index individual elements within a forest, which requires only minimal amounts of memory allowing for efficient and scalable algorithms of mesh management. In contrast to existing solutions, t8code has the capability to manage an arbitrary number of tetrahedra, hexahedra, prisms and pyramids within the same mesh. With this poster we want to present the first official release (v1.0) of our software and give a quick overview over its main features. Besides presenting the core algorithms of t8code, we give application scenarios on how our library integrates into major simulation frameworks for weather forecasting, climate modeling and engineering; and how they benefit from our approach to do AMR. [1] https://github.com/DLR-AMR/t8code [2] https://epubs.siam.org/doi/abs/10.1137/20M138303