Predicting the cost-effectiveness of strategies for case management of "plasmodium falciparum" malaria in Sub-Saharan Africa

Malaria is an important cause of death and illness in children and adults, particularly in the tropics. The World Health Organization (WHO) estimated that, worldwide, there were 655,000 malaria deaths in 2010, of which 91% were in Africa, and 216 million cases, of which 91% were due to Plasmodium falciparum (P.falciparum). However, case estimates are particularly uncertain, due to the ambiguous definition of a malaria case and methods used for their quantification. Efficacious interventions against malaria exist, but it is not clear what their full impact will be or how they could be most efficiently implemented. A cornerstone of malaria strategies is case management, which consists primarily of administering drug treatment to cure the disease, and was the focus of this thesis. Currently, the aim of most countries in sub-Saharan Africa is to control malaria and reduce the disease burden by increasing coverage of effective preventive and curative interventions. However, in some places successes in reducing disease burden have lead countries to consider whether and how local interruption of malaria transmission could be achieved and maintained. In these settings, improved surveillance is critical, but it is not clear what it should consist of. It is important to consider the long-term effects of intervention and intervention combinations, such as the dynamic effects on population immunity, which are not captured within the time frame of intervention trials, and their impact in real health systems. Mathematical models can offer guidance in these situations. In 2006, Smith and colleagues presented individual-based stochastic simulation models of the biology and epidemiology of P. falciparum malaria. As part of this project, a model for the case management of malaria was developed which permitted simulation of the dynamic effects of treatment on transmission. For this thesis, these models were extended to low-transmission settings and used to predict the levels of passive case detection and treatment that would be needed to prevent local re-establishment of transmission in different settings. We assessed the uncertainties in model predictions resulting from stochastic variation and from the assumptions in our model formulations. We found that, even at rather low levels of receptivity, case management alone could not reliably prevent re-establishment of P. falciparum malaria transmission in the face of medium to high importation rates. Model assumptions regarding rates of decay of natural immunity resulted in significantly different odds of transmission re-establishment, highlighting the urgent need for research in this area. We also developed a literature-based estimate of the per-person cost of screening an entire population for P.falciparum infection using diagnostic tests. We used this cost estimate along with simulation model outputs to analyse the cost-effectiveness of mass screening and treatment (MSAT) as a burden-reducing intervention, relative to the cost-effectiveness of scaling up case management or insecticide-treated net (ITN) coverage. We found that MSAT may be a cost-effective strategy at medium to high transmission levels and at moderate ITN coverage. This finding is in contrast to the current focus on MSAT as an intervention for low or near-elimination settings. Future analyses comparing the cost-effectiveness of case management with that of preventive interventions should include both disability and deaths averted (expressed in DALYs) as an outcome measure. The analysis also highlighted the need for alternative measures of uncomplicated malaria burden to capture the impact of case management in simulation models of its cost-effectiveness. An approach to do this, using data available in community surveys, is presented in this thesis. Finally, the previous case management model was extended to allow a finer-grained simulation of health systems and a drug action model was integrated to allow simulation of the effects of case management on parasite densities. The development and parameterization of the new case management model, and its potential future uses and limitations, are presented in the last sections of this thesis

Modeling Manifest Huntington's Disease Prevalence Using Diagnosed Incidence and Survival Time

Introduction: Understanding the epidemiology of Huntington's disease (HD) is key to assessing disease burden and the healthcare resources required to meet patients' needs. We aimed to develop and validate a model to estimate the diagnosed prevalence of manifest HD by the Shoulson-Fahn stage. Methods: A literature review identified epidemiological data from Brazil, Canada, France, Germany, Italy, Spain, the UK, and the USA. Data on staging distribution at diagnosis, progression, and mortality were derived from Enroll-HD. Newly diagnosed patients with manifest HD were simulated by applying annual diagnosed incidence rates to the total population in each country, each year from 1950 onwards. The number of diagnosed prevalent patients from the previous year who remained in each stage was estimated in line with the probability of death or progression. Diagnosed prevalence in 2020 was estimated as the sum of simulated patients, from all the incident cohorts, still alive. Results: The model estimates that in 2020, there were 66,787 individuals diagnosed with HD in the 8 included countries, of whom 62–63% were in Shoulson-Fahn stages 1 and 2 (with less severely limited functional capacity than those in stages 3–5). Diagnosed prevalence is estimated to be 8.2–9.0 per 100,000 in the USA, Canada, and the 5 included European countries and 3.5 per 100,000 in Brazil. Conclusion: The modeled estimates generally accord with the previously published data. This analysis contributes to better understanding of the epidemiology of HD and highlights areas of uncertainty

Childhood in Sociology and Society: The US Perspective

The field of childhood studies in the US is comprised of cross-disciplinary researchers who theorize and conduct research on both children and youth. US sociologists who study childhood largely draw on the childhood literature published in English. This article focuses on American sociological contributions, but notes relevant contributions from non-American scholars published in English that have shaped and fueled American research. This article also profiles the institutional support of childhood research in the US, specifically outlining the activities of the ‘Children and Youth’ Section of the American Sociological Association (ASA), and assesses the contributions of this area of study for sociology as well as the implications for an interdisciplinary field.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

How do parents experience being asked to enter a child in a randomised controlled trial?

<p>Abstract</p> <p>Background</p> <p>As the number of randomised controlled trials of medicines for children increases, it becomes progressively more important to understand the experiences of parents who are asked to enrol their child in a trial. This paper presents a narrative review of research evidence on parents' experiences of trial recruitment focussing on qualitative research, which allows them to articulate their views in their own words.</p> <p>Discussion</p> <p>Parents want to do their best for their children, and socially and legally their role is to care for and protect them yet the complexities of the medical and research context can challenge their fulfilment of this role. Parents are simultaneously responsible for their child and cherish this role yet they are dependent on others when their child becomes sick. They are keen to exercise responsibility for deciding to enter a child in a trial yet can be fearful of making the 'wrong' decision. They make judgements about the threat of the child's condition as well as the risks of the trial yet their interpretations often differ from those of medical and research experts. Individual pants will experience these and other complexities to a greater or lesser degree depending on their personal experiences and values, the medical situation of their child and the nature of the trial. Interactions at the time of trial recruitment offer scope for negotiating these complexities if practitioners have the flexibility to tailor discussions to the needs and situation of individual parents. In this way, parents may be helped to retain a sense that they have acted as good parents to their child whatever decision they make.</p> <p>Summary</p> <p>Discussing randomised controlled trials and gaining and providing informed consent is challenging. The unique position of parents in giving proxy consent for their child adds to this challenge. Recognition of the complexities parents face in making decisions about trials suggests lines for future research on the conduct of trials, and ultimately, may help improve the experience of trial recruitment for all parties.</p

Disease severity and mortality in Alzheimer's disease: an analysis using the U.S. National Alzheimer’s Coordinating Center Uniform Data Set

Abstract Background Evidence on the relative risk of death across all stages of Alzheimer’s disease (AD) is lacking but greatly needed for the evaluation of new interventions. We used data from the Uniform Data Set (UDS) of the National Alzheimer’s Coordinating Center (NACC) to assess the expected survival of a person progressing to a particular stage of AD and the relative risk of death for a person in a particular stage of AD compared with cognitively normal (CN) people. Methods This was a retrospective observational cohort study of mortality and its determinants in participants with incident mild cognitive impairment (MCI) due to AD or AD dementia compared with CN participants. Overall survival and hazard ratios of all-cause mortality in participants ≥ 50 years of age with clinically assessed or diagnosed MCI due to AD, or mild, moderate, or severe AD dementia, confirmed by Clinical Dementia Rating scores, versus CN participants were estimated, using NACC UDS data. Participants were followed until death, censoring, or until information to determine disease stage was missing. Results Aged between 50 and 104 years, 12,414 participants met the eligibility criteria for the study. Participants progressing to MCI due to AD or AD dementia survived a median of 3–12 years, with higher mortality observed in more severe stages. Risk of death increased with the severity of AD dementia, with the increase significantly higher at younger ages. Participants with MCI due to AD and CN participants had a similar risk of death after controlling for confounding factors. Conclusions Relative all-cause mortality risk increases with AD severity, more so at younger ages. Mortality does not seem to be higher for those remaining in MCI due to AD. Findings might imply potential benefit of lower mortality if preventing or delaying the progression of AD is successful, and importantly, this potential benefit might be greater in relatively younger people. Future research should replicate our study in other samples more representative of the general US population as well as other populations around the world

Estimated global resources needed to attain international malaria control goals

OBJECTIVE: To provide the international community with an estimate of the amount of financial resources needed to scale up malaria control to reach international goals, including allocations by country, year and intervention as well as an indication of the current funding gap. METHODS: A costing model was used to estimate the total costs of scaling up a set of widely recommended interventions, supporting services and programme strengthening activities in each of the 81 most heavily affected malaria-endemic countries. Two scenarios were evaluated, using different assumptions about the effect of interventions on the needs for diagnosis and treatment. Current health expenditures and funding for malaria control were compared to estimated needs. FINDINGS: A total of US$38 to 45 billion will be required from 2006 to 2015. The average cost during this period is US$ 3.8 to 4.5 billion per year. The average costs for Africa are US$1.7 billion and US$ 2.2 billion per year in the optimistic and pessimistic scenarios, respectively; outside Africa, the corresponding costs are US$2.1 billion and US$ 2.4 billion. CONCLUSION: While these estimates should not be used as a template for country-level planning, they provide an indication of the scale and scope of resources required and can help donors to collaborate towards meeting a global benchmark and targeting funding to countries in greatest need. The analysis highlights the need for much greater resources to achieve the goals and targets for malaria control set by the international community