Analysis of differential-delay equations for biology

In this thesis, we investigate the role of time delay in several differential-delay equation focusing on the negative autogenous regulation. We study these models for little or no delay to when the model has a very large delay parameter. We start with the logistic differential-delay equation applying techniques that would be used in subsequent chapters for other models being studied. A key goal of this research is to identify where the structure of the system does change. First, we investigate these models for critical point and study their behaviour close to these points. Of keen interest is the Hopf bifurcation points where we analyse the parameter associated with the Hopf point. The weakly nonlinear analysis carried out using the method of multiple time scale is used to give more insight to these model. The centre manifold method is shown to support the result derived using the multiple time scale. Then the second study carried out is the study of the transition from a sinelike wave to a square wave. This is analysed and a scale deduced at which this transition gradually takes place. One of the key areas we focused on in the large delay is to solve for a certain constant a' associated with the period of oscillation. The effect of the delayed parameter is shown throughout this thesis as a major contributor to the properties of both the logistic delay and the negative autogenous regulation

After Three Centuries of Migration, What Happened to the Children?

Migration within the last three centuries centres on economics, shifts in government policies, and general concepts surrounding migrating children. However, this chapter asks a fundamental question, ‘what happened to the children? Over the last three centuries, children have been born along the journey. Accompanied and unaccompanied children have been and continue to be the forgotten collateral damage. The chapter explores the critical role of protection, prevention, and harm to migrating children. It addresses gaps and noncompliance with the ratified treaty, the UN Convention on the Rights of the Child over the last three decades, international migration in countries of origin, transit, destination, and return, to include the lifetime of impact on their health

Prevention of Postpartum Haemorrhage: Economic evaluation of the novel Butterfly device in a UK setting

ObjectivesTo explore the cost-effectiveness of a novel PPH device as compared with usual care.DesignA decision analytical model was used to explore the cost-effectiveness of the PPH Butterfly device compared with usual care. This was part of a United Kingdom, UK, clinical trial ISRCTN15452399 using a matched historical cohort who had standard PPH management without the use of the PPH Butterfly device. The economic evaluation was conducted from a UK National Health Service (NHS) perspective.SettingLiverpool Women's Hospital, UK.Participants57 women with 113 matched controls.InterventionThe PPH Butterfly is a novel device that has been invented and developed in the UK to facilitate bimanual compression of the uterus in the treatment of PPH.Main outcome measuresMain outcome measures included healthcare costs, blood loss, and maternal morbidity events.ResultsMean treatment costs in the Butterfly cohort were £3,459.66 as compared with standard care £3,223.93. Treatment with the Butterfly device resulted in decreased total blood loss in comparison with standard care. The Butterfly device had an incremental cost-effectiveness ratio of £3,795.78 per PPH progression avoided (defined as ≤ 1000 ml additional blood loss from device insertion point). If the NHS is prepared to pay £8,500 per PPH progression avoided, then the Butterfly device is cost-effective with a probability of 87 percent. In the PPH Butterfly treatment arm there were 9% fewer cases of massive obstetric haemorrhage (severe PPH of more than 2000mls or more than 4 units of blood transfusion required) recorded as compared with the standard care historical cohort. As a low-cost device, the PPH Butterfly device is cost-effective but can be cost-saving to the NHS.ConclusionThe PPH pathway can result in high-cost resource use such as blood transfusion or high dependence unit hospital stays. The Butterfly device is a relative low-cost device in a UK NHS setting with a high probability of being cost-effective. The National Institute for Health and Care Excellence (NICE) can use this evidence in considering the adoption of innovative technologies such as the Butterfly device in the NHS. Extrapolation on an international scale to lower and middle-income countries could prevent mortality associated with PPH

Cost-effectiveness Analysis of the Dental RECUR Pragmatic Randomized Controlled Trial: Evaluating a Goal-oriented Talking Intervention to Prevent Reoccurrence of Dental Caries in Children

BACKGROUND: The formation of dental caries is the most common chronic disease in children, and is preventable. The oral health-related quality of life has an immense impact on an individual’s daily functioning, well-being or overall quality of life. OBJECTIVES: This study aims to investigate the cost effectiveness of the Dental RECUR Brief Negotiated Interview for Oral Health (DR-BNI). This 30-minute therapeutic “talk” by a dental nurse with a parent/guardian was compared with a placebo-controlled intervention in preventing reoccurrence of dental caries in children who have had a primary tooth extracted. METHODS: An economic model was developed to simulate the clinical progression of dental caries among children who have previously had a primary tooth extracted. The analysis was conducted using the UK NHS perspective. The main outcome was the incremental cost-effectiveness ratio (ICER) based on the quality-adjusted life years (QALYs). Estimates of costs and probabilities were obtained from the DR-BNI multicentre randomised controlled trial (RCT), while QALY values were obtained from published literature. Univariate and probabilistic sensitivity analyses were conducted to assess the uncertainty of the result and robustness of the model. Affordability and risk-aversion of the intervention were investigated to help decision makers make the best possible choices. RESULTS: With an intervention cost of £6.47, the results from the RCT showed the healthcare cost for the DR-BNI intervention was £115.90 per child while the control had a healthcare cost of £119.46 per child. The QALYs gained for the prevention of reoccurrence of dental caries was higher in the DR-BNI intervention arm by 0.023 QALYs; thus, the DR-BNI was the dominant intervention. At willingness to pay threshold of £3500/QALY gained, a maximum probability of being cost effectiveness is achieved at 86%. The secondary analysis showed a cost-savings of £20.94 per participant for the prevention of at least one filling or extraction. Affordability results showed that the DR-BNI programme is affordable to the UK health system at a moderately low budget. CONCLUSIONS: This study shows the proactive talking intervention to have a very moderate cost and to be effective in providing better health related quality-of-life gains. The intervention is cost savings with a dominant ICER even with a 200% increase in the cost of intervention. The NHS will be providing better oral health for children at a better net monetary benefit-to-risk ratio by adopting the DR-BNI intervention in preventing the reoccurrence of dental fillings and extractions for each participant. Trial Registration: This trial was registered prospectively on 27th September 2013 with the trial registration number ISRCTN 24958829. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40258-022-00720-5

Protocol for the Rare Dementia Support Impact Study: RDS Impact

OBJECTIVES: The Rare Dementia Support (RDS) Impact study will be the first major study of the value of multicomponent support groups for people living with or supporting someone with a rare form of dementia. The multicentre study aims to evaluate the impact of multicomponent support offered and delivered to people living with a rare form of dementia, comprising the following five Work Packages (WPs): (1) Longitudinal cohort interviews; (2) Theoretical development; (3) Developing measures; (4) Novel interventions; and (5) Economic analysis. METHODS: This is a mixed-methods design, including a longitudinal cohort study (quantitative and qualitative) and a feasibility randomised control trial (RCT). A cohort of >1000 individuals will be invited to participate. The primary and secondary outcomes will be in-part determined through a co-design Nominal Groups Technique pre-study involving caregivers to people living with a diagnosis of a rare dementia. Quantitative analyses of differences and predictors will be based on pre-specified hypotheses. A variety of quantitative (e.g. ANOVA and multiple linear regression techniques), qualitative (e.g. thematic analysis) and innovative analytical methods will also be developed and applied by involving the arts as a research method. RESULTS: The UCL Research Ethics Committee have approved this study. Data collection will begin in Q4 2019. CONCLUSIONS: The study will capture information through a combination of longitudinal interviews, questionnaires and scales, and novel creative data collection methods. The notion of 'impact' in the context of support for rare dementias will involve theoretical development, novel measures and methods of support interventions, and health economic analyses