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To examine the costs and cost-effectiveness of mirtazapine compared to placebo over 12-week follow-up.
Economic evaluation in a double-blind randomized controlled trial of mirtazapine vs. placebo.
Community settings and care homes in 26 UK centers.
People with probable or possible Alzheimer’s disease and agitation.
Primary outcome included incremental cost of participants’ health and social care per 6-point difference in CMAI score at 12 weeks. Secondary cost-utility analyses examined participants’ and unpaid carers’ gain in quality-adjusted life years (derived from EQ-5D-5L, DEMQOL-Proxy-U, and DEMQOL-U) from the health and social care and societal perspectives.
One hundred and two participants were allocated to each group; 81 mirtazapine and 90 placebo participants completed a 12-week assessment (87 and 95, respectively, completed a 6-week assessment). Mirtazapine and placebo groups did not differ on mean CMAI scores or health and social care costs over the study period, before or after adjustment for center and living arrangement (independent living/care home). On the primary outcome, neither mirtazapine nor placebo could be considered a cost-effective strategy with a high level of confidence. Groups did not differ in terms of participant self- or proxy-rated or carer self-rated quality of life scores, health and social care or societal costs, before or after adjustment.
On cost-effectiveness grounds, the use of mirtazapine cannot be recommended for agitated behaviors in people living with dementia. Effective and cost-effective medications for agitation in dementia remain to be identified in cases where non-pharmacological strategies for managing agitation have been unsuccessful.
Among bilinguals, language-related variables such as first and second language proficiency and balance may be related to important cognitive and academic outcomes, but approaches to characterizing these variables are inconsistent, particularly among at-risk samples of children. The current study employed comprehensive language assessment of English and Spanish language skills and contrasted various approaches to the characterization of language among at-risk ELs in middle school (N = 161). Specifically, we contrasted variable-centered and person-centered approaches, and convergence between objective and self-report measures. Findings support a two-factor structure of English and Spanish language skills in this population, three profiles of students (balanced, moderately unbalanced-higher Spanish, and very unbalanced-higher English), convergence between variable-centered and person-centered approaches, and mixed support for subjective indices of usage. Results provide a foundation from which to examine the roles of L1 and L2 proficiency as well as balance in important cognitive and academic outcomes in this at-risk and understudied population.
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Marine science picture books have the capacity to shape what young people know and how they think about ocean environments and marine biodiversity. Despite academic scholarship on marine science literacy broadly, relatively little has been done to study the role of picture books in teaching children about this topic. This paper is an attempt to fill that gap, by analysing 100 ocean-themed books against common marine science concepts and the Australian Science Understanding Curriculum streams. A majority of the 100 books analysed were found to link with marine science and the Australian Science Understanding Curriculum (81% and 91%, respectively) where biological concepts were dominant in both cases. Chemical and physical sciences were underrepresented in the 100 books analysed. The study provides examples of books that can be used for teaching marine education in primary schools in Australia and suggest further inquiry into marine science literature for children.
Policy making increasingly needs cost-effectiveness evidence to inform resource allocation. The objective of this review is to identify and to investigate evidence evaluating the cost-effectiveness of interventions aimed to support adult carers, drawing on the National Institute for Health and Care guideline on Supporting Adult Carers.
The protocol of the review was aimed to identify the economic studies published from 2003 onwards on all types of interventions for supporting adult carers. The applicability to the review and methodological quality of included economic evaluations were assessed using pre-established checklists specified in the National Institute for Health and Care (NICE) manual for developing guidelines.
Our search yielded 10 economic evaluations. The main types of strategies evaluated were psychological and emotional support, training, and education support interventions. We found that the interventions more likely to be cost-effective were usually tailored to the specific carers’ circumstances and delivered face-to-face and were multi-component in nature, including elements of psycho-education, training, psychological and practical support. The narrative synthesis of results indicated a wide variation in cost-effectiveness findings and methodological quality.
This article indicates that systematic reviews of economic evaluations can be considered as an appropriate means to support decision makers in allocating health and social care resources. Given the high economic and social impact of unpaid caring, and based on the research gaps identified, we recommend that future economics research should be targeted on interventions for identifying carers; and programs for providing carers with support and advice to help them to enter, remain in or return to paid work.
Mercury is a volcanic world: the planet has experienced a geological history that included partial melting of the interior and the transport of magma to, and eruption onto, the surface. In this chapter, we review Mercury’s volcanic character, first in terms of effusive volcanism (as characterized by lava plains, erosional landforms, and spectral characteristics), next in regard to the planet’s explosive volcanic activity, and then from the perspective of intrusive magmatism. We also visit the planet’s ancient yet spatially expansive intercrater plains and the prospect that they, too, are volcanic. We combine the observations of and inferences for Mercury’s smooth and intercrater plains to propose a model for the planet’s crustal stratigraphy. The extent of our understanding of the petrology of surface materials on Mercury is then discussed, including compositions and lithologies, mineral assemblages, physicochemical properties, and volatile contents. We then describe in broad terms the history of effusive and explosive volcanism on the planet, before addressing the influence that the planet’s lithospheric properties and tectonic evolution have played on volcanism. We finish by listing some major outstanding questions pertaining to the volcanic character of Mercury, and we suggest how those questions might best be addressed.
Most of the African countries are undergoing a complex nutrition and epidemiologic transition associated with a rapid increase in the prevalence of diverse non-communicable diseases. Despite this alarming situation, the still limited and fragmented resources available in Africa impede the implementation of effective action plans to tackle the current and projected diet–disease burden. In order to address these common needs and challenges, the African Union is increasingly supporting continental approaches and strategies as reflected in the launching of the Agenda 2063 and the African regional nutrition strategy 2015–2025, among others. To assure the successful implementation of pan-African nutritional and health initiatives, cost-effective approaches considering similarities/disparities in economy, regional integration, development and nutritional aspects between countries are needed. In the absence of pre-existing models, we reviewed regional economic integration and nutritional indicators (n 13) available in international organisations databases or governmental agencies websites, for fifty-two African countries. These indicators were used to map the countries according to common languages (e.g. Arabic, English, French, Portuguese), development status (e.g. human development index), malnutrition status (e.g. obesity) and diet (e.g. staples predominantly based on either cereals or tubers). The review of the indicators showed that there exist similarities between African countries that can be exploited to benefit the continent with cross-national experiences in order to avoid duplication of efforts in the implementation of future pan-African health studies. In addition, including present and future nutrition surveillance programmes in Africa into national statistical systems might be cost-effective and sustainable in the longer term.
Addressing contemporary nutrition problems often requires application of knowledge from multiple disciplines. The scaling up nutrition (SUN) movement harnesses multiple sectors for effective global and in-country planning and implementation. Although the role of knowledge networks (academia and research institutions) is recognised, the how of engaging knowledge networks in the current SUN architecture is only now becoming apparent. For relevant sectors to play their roles effectively, observed capacity gaps, particularly in developing country settings, need to be addressed. The present paper presents the work being undertaken by the Ghana SUN Academic Platform (AP), a local knowledge network, towards strengthening nutrition capacity in Ghana. The AP presently provides technical support, evidence and capacity towards scaling up effective nutrition interventions in Ghana and beyond. The data presented draws heavily on the observations and collective experiences of the authors in practice, complemented by a review of relevant literature. The ultimate goal of the AP is to build capacity of professionals from nutrition and cognate sectors (including planning, agriculture, health, economics, research and academia). This is an essential ingredient for effective and durable SUN efforts. The paper recognises that both disciplinary and interdisciplinary capacity is required for effective SUN efforts in Africa, and offers an approach that utilises cross-sector/inter-professional, peer-learning and experiential learning initiatives.
North-central Africa (i.e. Cameroon, the Central African Republic and Chad) once held important populations of large mammals, including the hippopotamus Hippopotamus amphibius. Exports of hippopotamus trophies from Cameroon were suspended in 2012 but the species’ status and population trends remain poorly known. Using the same methodology as in 2000 and 2008, we counted hippopotamuses in Faro National Park and bordering hunting zones in 2014. We counted 685 individuals along 97 km of river, compared with 647 and 525 in 2000 and 2008, respectively. The stability of this population contrasts with the declines in populations of large mammals across north-central Africa. We attribute this conservation success to private efforts (i.e. safari hunting) compensating for a decline in state protection. However, the situation remains fragile, as highlighted by an influx of transhumant cattle and gold diggers. We recommend increasing public–private conservation efforts, including incentives for the safari hunting industry, which is also under pressure.
The use of artificial neural networks (ANNs) as a classifier of digital spectra is investigated. Using both simulated and real data, it is shown that neural networks can be trained to discriminate between the spectra of different classes of active galactic nucleus (AGN) with realistic sample sizes and signal-to-noise ratios. By working in the Fourier domain, neural nets can classify objects without knowledge of their redshifts.