High-gain nonlinear observer for simple genetic regulation process

High-gain nonlinear observers occur in the nonlinear automatic control theory and are in standard usage in chemical engineering processes. We apply such a type of analysis in the context of a very simple one-gene regulation circuit. In general, an observer combines an analytical differential-equation-based model with partial measurement of the system in order to estimate the non-measured state variables. We use one of the simplest observers, that of Gauthier et al., which is a copy of the original system plus a correction term which is easy to calculate. For the illustration of this procedure, we employ a biological model, recently adapted from Goodwin's old book by De Jong, in which one plays with the dynamics of the concentrations of the messenger RNA coding for a given protein, the protein itself, and a single metabolite. Using the observer instead of the metabolite, it is possible to rebuild the non-measured concentrations of the mRNA and the proteinComment: 9 pages, one figur

Trends in direct oral anticoagulant (DOAC) use:Health benefits and patient preference

In 2012, the Dutch Health Council published a report addressing barriers for an early and broad introduction of direct oral anticoagulants (DOACs). The report raised concerns about the lack of an antidote, adherence, lack of monitoring in the case of overdose and the increased budget impact at DOAC introduction. In the past decade, international studies have shown that DOACs can provide healthcare benefits for a large number of patients. This has led to an increase in the prescription of DOACs, as they are an effective and user-friendly alternative to vitamin K antagonists (VKAs). Unlike VKAs, DOACs do not need monitoring of the international normalized ratio due to more predictable pharmacokinetics. However, the number of prescriptions of DOACs in the Netherlands is still lagging, compared to other European countries. This article highlights the potential health gains in the Netherlands if the use of DOACs were to increase, based on current international experience

Effectiveness of the beyond good intentions program on improving dietary quality among people with Type 2 Diabetes Mellitus: a randomized controlled trial

Background and Aims: An appropriate diet is an essential component of the management of Type 2 Diabetes Mellitus (T2DM). However, for many people with T2DM, self-management is difficult. Therefore, the Beyond Good Intentions (BGI) education program was developed based on self-regulation and proactive coping theories to enhance people's capabilities for self-management. The aim of this study was to determine the effectiveness of the BGI program on improving dietary quality among a preselected group of people with T2DM after two-and-a-half years follow-up.Methods: In this randomized controlled trial, 108 people with T2DM were randomized (1:1) to the intervention (n = 56) (BGI-program) or control group (n = 52) (care as usual). Linear regression analyses were used to determine the effect of the BGI program on change in dietary quality between baseline and two-and-a-half years follow-up. In addition, potential effect modification by having a nutritional goal at baseline was evaluated. Multiple imputation (n = 15 imputations) was performed to account for potential bias due to missing data.Results: According to intention-to-treat analysis, participants in the intervention group showed greater improvements in dietary quality score than participants in the control group (beta = 0.71; 95%CI: 0.09; 1.33) after follow-up. Having a nutritional goal at baseline had a moderating effect on the effectiveness of the BGI program on dietary quality (p-interaction = 0.01), and stratified results showed that the favorable effect of the intervention on dietary quality was stronger for participants without a nutritional goal at baseline (no nutritional goal: beta = 1.46; 95%CI: 0.65; 2.27 vs. nutritional goal: beta = -0.24; 95%CI: -1.17; 0.69).Conclusions: The BGI program was significantly effective in improving dietary quality among preselected people with T2DM compared to care as usual. This effect was stronger among participants without a nutritional goal at baseline. A possible explanation for this finding is that persons with a nutritional goal at baseline already started improving their dietary intake before the start of the BGI program. Future studies are needed to elucidate the moderating role of goalsetting on the effectiveness of the BGI program.Prevention, Population and Disease management (PrePoD)Public Health and primary car

Budget impact of optimizing rifaximin-alpha use for the prevention of recurrent hepatic encephalopathy in The Netherlands

Aims Rifaximin-alpha as an adjunct to lactulose is reimbursed in the Netherlands for prevention of the third and subsequent episodes of overt Hepatic Encephalopathy (HE) in cirrhotic patients. However, use of rifaximin-alpha remains limited. This study evaluates the clinical and economic impact of treating all patients eligible under Dutch reimbursement conditions with rifaximin-alpha as an adjunct to lactulose for the prevention of overt HE in the Netherlands from a hospital and healthcare payer's perspective. Materials and methods A budget impact analysis was performed following national and international guidelines. Resource use was based on Dutch real-world data. HE-related cost inputs were based on the declaration codes, Dutch cost manual, and actual drug list prices. Several sensitivity and scenario analyses were conducted to assess model robustness. Results Treating eligible HE patients with rifaximin-alpha in addition to lactulose saves euro4,487 and costs euro249 per patient over a 5-year period compared with lactulose monotherapy from hospital and healthcare payer's perspectives, respectively. In the Netherlands, an estimated 38% of the 2,567 eligible patients are currently being treated with rifaximin-alpha. Optimizing rifaximin-alpha use by treating all eligible patients with the rifaximin-alpha + lactulose could save more than 3,000 hospital admissions, almost 15,000 hospital bed days, and 300 deaths over a 5-year period. Despite increased drug costs, treatment is estimated to result in potential cost savings over a 5-year period of 7.2 million euros from a Dutch hospital perspective. The budget impact is 397,770 euros from a healthcare payer's perspective. Conclusions Next to a clinical perspective, also from an economic perspective, wider prescription of rifaximin-alpha adhering to guidelines could be beneficial to reduce costs from a hospital perspective. From a healthcare payer's perspective, costs increase with addition of rifaximin-alpha due to relative better survival causing relatively higher drug and liver transplantation-related costs.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Extending the theory of planned behavior for explaining dietary quality: the role of financial scarcity and food insecurity status

ObjectiveTo examine whether an extended Theory of Planned Behavior (TPB) that included finance-related barriers better explained dietary quality.DesignCross-sectional survey.ParticipantsOne-thousand and thirty-three participants were included from a Dutch independent adult panel.Main OutcomeDietary quality.AnalysisFive TPB models were assessed: a traditional TPB, a TPB that included direct associations between attitude and subjective norm with dietary quality, a TPB that additionally included financial scarcity or food insecurity, and a TPB that additionally included financial scarcity and food insecurity simultaneously. Structural relationships among the constructs were tested to compare the explanatory power.ResultsThe traditional TPB showed poorest fit (χ2/degrees of freedom = 11; comparative fit index = 0.75; root mean square error of approximation [95% confidence interval], 0.10 [0.091–0.12]; standardized root mean square residual = 0.049), the most extended TPB (including both financial scarcity and food insecurity) showed best fit (χ2/degrees of freedom = 3.3; comparative fit index = 0.95; root mean square error of approximation [95% confidence interval], 0.050 [0.035–0.065]; standardized root mean square residual = 0.018). All 5 structure models explained ∼42% to 43% of the variance in intention; however, the variance in dietary quality was better explained by the extended TPB models, including food insecurity and/or financial scarcity (∼22%) compared with the traditional TBP (∼7%), indicating that these models better explained differences in dietary quality.Conclusions and ImplicationsThese findings highlight the importance of accounting for finance-related barriers to healthy eating like financial scarcity or food insecurity to better understand individual dietary behaviors in lower socioeconomic groups.Social decision makin

Companion Animals as a Source of Viruses for Human Beings and Food Production Animals

Companion animals comprise a wide variety of species, including dogs, cats, horses, ferrets, guinea pigs, reptiles, birds and ornamental fish, as well as food production animal species, such as domestic pigs, kept as companion animals. Despite their prominent place in human society, little is known about the role of companion animals as sources of viruses for people and food production animals. Therefore, we reviewed the literature for accounts of infections of companion animals by zoonotic viruses and viruses of food production animals, and prioritized these viruses in terms of human health and economic importance. In total, 138 virus species reportedly capable of infecting companion animals were of concern for human and food production animal health: 59 of these viruses were infectious for human beings, 135 were infectious for food production mammals and birds, and 22 were infectious for food production fishes. Viruses of highest concern for human health included hantaviruses, Tahyna virus, rabies virus, West Nile virus, tick-borne encephalitis virus, Crimean-Congo haemorrhagic fever virus, Aichi virus, European bat lyssavirus, hepatitis E virus, cowpox virus, G5 rotavirus, influenza A virus and lymphocytic choriomeningitis virus. Viruses of highest concern for food production mammals and birds included bluetongue virus, African swine fever virus, foot-and-mouth disease virus, lumpy skin disease virus, Rift Valley fever virus, porcine circovirus, classical swine fever virus, equine herpesvirus 9, peste des petits ruminants virus and equine infectious anaemia virus. Viruses of highest concern for food production fishes included cyprinid herpesvirus 3 (koi herpesvirus), viral haemorrhagic septicaemia virus and infectious pancreatic necrosis virus. Of particular concern as sources of zoonotic or food production animal viruses were domestic carnivores, rodents and food production animals kept as companion animals. The current list of viruses provides an objective basis for more in-depth analysis of the risk of companion animals as sources of viruses for human and food production animal health

Needs and perceptions regarding healthy eating among people at risk of food insecurity: A qualitative analysis

Background: Healthy eating behaviour is an essential determinant of overall health. This behaviour is generally poor among people at risk of experiencing food insecurity, which may be caused by many factors including perceived higher costs of healthy foods, financial stress, inadequate nutritional knowledge, and inadequate skills required for healthy food preparation. Few studies have examined how these factors influence eating behaviour among people at risk of experiencing food insecurity. We therefore aimed to gain a better understanding of the needs and perceptions regarding healthy eating in this target group. Methods: We conducted a qualitative exploration grounded in data using inductive analyses with 10 participants at risk of experiencing food insecurity. The analysis using an inductive approach identified four core factors influencing eating behaviour: Health related topics; Social and cultural influences; Influences by the physical environment; and Financial influences. Results: Overall, participants showed adequate nutrition knowledge. However, eating behaviour was strongly influenced by both social factors (e.g. child food preferences and cultural food habits), and physical environmental factors (e.g. temptations in the local food environment). Perceived barriers for healthy eating behaviour included poor mental health, financial stress, and high food prices. Participants had a generally conscious attitude towards their financial situation, reflected in their strategies to cope with a limited budget. Food insecurity was mostly mentioned in reference to the past or to others and not to participants' own current experiences. Participants were familiar with several existing resources to reduce food-related financial strain (e.g. debt assistance) and generally had a positive attitude towards these resources. An exception was the Food Bank, of which the food parcel content was not well appreciated. Proposed interventions to reduce food-related financial strain included distributing free meals, facilitating social contacts, increasing healthy food supply in the neighbourhood, and lowering prices of healthy foods. Conclusion: The insights from this study increase understanding of factors influencing eating behaviour of people at risk of food insecurity. Therefore, this study could inform future development of potential interventions aiming at helping people at risk of experiencing food insecurity to improve healthy eating, thereby decreasing the risk of diet-related diseases