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Depression is common in people with dementia, and negatively affects quality of life.
Aims
This paper aims to evaluate the cost-effectiveness of an intervention for depression in mild and moderate dementia caused by Alzheimer's disease over 12 months (PATHFINDER trial), from both the health and social care and societal perspectives.
Method
A total of 336 participants were randomised to receive the adapted PATH intervention in addition to treatment as usual (TAU) (n = 168) or TAU alone (n = 168). Health and social care resource use were collected with the Client Service Receipt Inventory and health-related quality-of-life data with the EQ-5D-5L instrument at baseline and 3-, 6- and 12-month follow-up points. Principal analysis comprised quality-adjusted life-years (QALYs) calculated from the participant responses to the EQ-5D-5L instrument.
Results
The mean cost of the adapted PATH intervention was estimated at £1141 per PATHFINDER participant. From a health and social care perspective, the mean difference in costs between the adapted PATH and control arm at 12 months was −£74 (95% CI −£1942 to £1793), and from the societal perspective was −£671 (95% CI −£9144 to £7801). The mean difference in QALYs was 0.027 (95% CI −0.004 to 0.059). At £20 000 per QALY gained threshold, there were 74 and 68% probabilities of adapted PATH being cost-effective from the health and social care and societal perspective, respectively.
Conclusions
The addition of the adapted PATH intervention to TAU for people with dementia and depression generated cost savings alongside a higher quality of life compared with TAU alone; however, the improvements in costs and QALYs were not statistically significant.
In his Scroogenomics, Joel Waldfogel argues that gifting creates enormous deadweight loss, as individuals give one another gifts that they do not want or cannot use. He views efficiency as static, calculating the gains from trade (or gifting) at the moment of transaction. A puzzle arises, however, when one realizes that gifting has been a nearly ubiquitous institution throughout history. If gifting wastes valuable resources, why does it persist? We argue that gift giving is dynamically efficient despite the possibility of generating short-term deadweight loss. A well-functioning market economy requires expanded social networks and trustworthiness among anonymous and quasi-anonymous exchange partners. Gifting allows individuals to signal trustworthiness by offering ‘burnt sacrifices’. Gifting practices that include a willingness to sacrifice via reciprocity norms, public visibility and ritual will tend to promote generalized trust. We consider these four elements – sacrifice, reciprocity, publicness, and ritual – to be critical institutional design principles for fostering dynamic efficiency. Our essay contributes to the literature on institutional economics by prompting scholars to think about the long-term (dynamic) efficiencies generated by cultural practices that appear inexplicably inefficient.
To examine the costs and cost-effectiveness of mirtazapine compared to placebo over 12-week follow-up.
Design:
Economic evaluation in a double-blind randomized controlled trial of mirtazapine vs. placebo.
Setting:
Community settings and care homes in 26 UK centers.
Participants:
People with probable or possible Alzheimer’s disease and agitation.
Measurements:
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.
Results:
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.
Conclusions:
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.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) has high morbidity and mortality in older adults and people with dementia. Infection control and prevention measures potentially reduce transmission within hospitals.
Aims
We aimed to replicate our earlier study of London mental health in-patients to examine changes in clinical guidance and practice and associated COVID-19 prevalence and outcomes between COVID-19 waves 1 and 2 (1 March to 30 April 2020 and 14 December 2020 to 15 February 2021).
Method
We collected the 2 month period prevalence of wave 2 of COVID-19 in older (≥65 years) in-patients and those with dementia, as well as patients’ characteristics, management and outcomes, including vaccinations. We compared these results with those of our wave 1 study.
Results
Sites reported that routine testing and personal protective equipment were available, and routine patient isolation on admission occurred throughout wave 2. COVID-19 infection occurred in 91/358 (25%; 95% CI 21–30%) v. 131/344, (38%; 95% CI 33–43%) P < 0.001 in wave 1. Hospitals identified more asymptomatic carriers (26/91; 29% v. 16/130; 12%) and fewer deaths (12/91; 13% v. 19/131; 15%; odds ratio = 0.92; 0.37–1.81) compared with wave 1. The patient vaccination uptake rate was 49/58 (85%).
Conclusions
Patients in psychiatric in-patient settings, mostly admitted without known SARS-CoV-2 infection, had a high risk of infection compared with people in the community but lower than that during wave 1. Availability of infection control measures in line with a policy of parity of esteem between mental and physical health appears to have lowered within-hospital COVID-19 infections and deaths. Cautious management of vulnerable patient groups including mental health patients may reduce the future impact of COVID-19.
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.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
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.
Results
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.
Conclusions
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.
Unnecessarily delayed discharges from hospital of older people living with frailty can have negative consequences for their health and add significant costs to health services. We report on an ethnographic study at two English hospitals and their respective health and social care systems where we followed 37 patient journeys. The study aim was to understand why delays occur. Our findings indicate that working practices in the study hospitals may have inadvertently contributed to delays. While many pieces of patients’ clinical and social information were collected, recorded and accessed in different ways by different professionals, to facilitate a discharge, these pieces needed to be re-found, integrated and re-constructed. A key component of this process was information related to patients’ social, family and functional background. This was often missing, not accessed or perceived to be of low value compared to other more readily available clinical information. Patients’ re-construction was thus often incomplete, or insufficient to reduce the clinical and prognostic uncertainty associated with frailty and to manage risks inherent in older people's discharge. Where this key component was present and integrated into decision-making in multi-disciplinary team working, uncertainty and risk were managed more constructively and sometimes avoided an escalation of care needs.
The EVOSHEEP project combines archaeozoology, geometric morphometrics and genetics to study archaeological sheep assemblages dating from the sixth to the first millennia BC in eastern Africa, the Levant, the Anatolian South Caucasus, the Iranian Plateau and Mesopotamia. The project aims to understand changes in the physical appearance and phenotypic characteristics of sheep and how these related to the appearance of new breeds and the demand for secondary products to supply the textile industry.
We report on a two-arm hybrid high-power laser system (HPLS) able to deliver 2 × 10 PW femtosecond pulses, developed at the Bucharest-Magurele Extreme Light Infrastructure Nuclear Physics (ELI-NP) Facility. A hybrid front-end (FE) based on a Ti:sapphire chirped pulse amplifier and a picosecond optical parametric chirped pulse amplifier based on beta barium borate (BBO) crystals, with a cross-polarized wave (XPW) filter in between, has been developed. It delivers 10 mJ laser pulses, at 10 Hz repetition rate, with more than 70 nm spectral bandwidth and high-intensity contrast, in the range of 1013:1. The high-energy Ti:sapphire amplifier stages of both arms were seeded from this common FE. The final high-energy amplifier, equipped with a 200 mm diameter Ti:sapphire crystal, has been pumped by six 100 J nanosecond frequency doubled Nd:glass lasers, at 1 pulse/min repetition rate. More than 300 J output pulse energy has been obtained by pumping with only 80% of the whole 600 J available pump energy. The compressor has a transmission efficiency of 74% and an output pulse duration of 22.7 fs was measured, thus demonstrating that the dual-arm HPLS has the capacity to generate 10 PW peak power femtosecond pulses. The reported results represent the cornerstone of the ELI-NP 2 × 10 PW femtosecond laser facility, devoted to fundamental and applied nuclear physics research.
Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.
Policy-makers and practitioners have a need to assess community resilience in disasters. Prior efforts conflated resilience with community functioning, combined resistance and recovery (the components of resilience), and relied on a static model for what is inherently a dynamic process. We sought to develop linked conceptual and computational models of community functioning and resilience after a disaster.
Methods
We developed a system dynamics computational model that predicts community functioning after a disaster. The computational model outputted the time course of community functioning before, during, and after a disaster, which was used to calculate resistance, recovery, and resilience for all US counties.
Results
The conceptual model explicitly separated resilience from community functioning and identified all key components for each, which were translated into a system dynamics computational model with connections and feedbacks. The components were represented by publicly available measures at the county level. Baseline community functioning, resistance, recovery, and resilience evidenced a range of values and geographic clustering, consistent with hypotheses based on the disaster literature.
Conclusions
The work is transparent, motivates ongoing refinements, and identifies areas for improved measurements. After validation, such a model can be used to identify effective investments to enhance community resilience. (Disaster Med Public Health Preparedness. 2018;12:127–137)
Despite the potential of declared serving size to encourage appropriate portion size consumption, most countries including Australia have not developed clear reference guidelines for serving size. The present study evaluated variability in manufacturer-declared serving size of discretionary food and beverage products in Australia, and how declared serving size compared with the 2013 Australian Dietary Guideline (ADG) standard serve (600 kJ). Serving sizes were obtained from the Nutrition Information Panel for 4466 packaged, discretionary products in 2013 at four large supermarkets in Sydney, Australia, and categorised into fifteen categories in line with the 2013 ADG. For unique products that were sold in multiple package sizes, the percentage difference between the minimum and the maximum serving size across different package sizes was calculated. A high variation in serving size was found within the majority of food and beverage categories – for example, among 347 non-alcoholic beverages (e.g. soft drinks), the median for serving size was 250 (interquartile range (IQR) 250, 355) ml (range 100–750 ml). Declared serving size for unique products that are available in multiple package sizes also showed high variation, particularly for chocolate-based confectionery, with median percentage difference between minimum and maximum serving size of 183 (IQR 150) %. Categories with a high proportion of products that exceeded the 600 kJ ADG standard serve included cakes and muffins, pastries and desserts (≥74 % for each). High variability in declared serving size may confound interpretation and understanding of consumers interested in standardising and controlling their portion selection. Future research is needed to assess if and how standardising declared serving size might affect consumer behaviour.
This study assesses the variation between regional skeletal samples from prehistoric Easter Island on the basis of several discrete cranial traits to determine if there exists significant variation between tribal regions as described in the ethnographic record. The skeletal sample is divided into five groups representing regions of Easter Island that correspond to purported ancient tribal areas (Figure 7.1) and are compared to one another to test for statistically significant cranial trait variation with regards to specific discrete characteristics.
Due to their apparently strong genetic and low environmental factors affecting them, discrete traits are useful in population studies (Corruccini, 1974). Discrete cranial traits can be used to determine genetic distance between populations. They may also be useful in determining genetic distance within populations if political or social divisions influence gene flow between subpopulations such as tribes, clans, or kinship groups. Field observations and preliminary studies indicate that discrete traits do vary among early Easter Islanders. This study evaluates 30 cranial discrete traits and tests the hypothesis that no significant variation in cranial discrete traits exists between regional skeletal samples representing ancient Easter Island tribal areas.
Skeletal sample
The skeletons used here are from a pool of 426 individuals housed at the Sebastian Englert Museum of Anthropology, Easter Island, Chile. Much of this sample was collected by the 1981 Easter Island Anthropological Expedition, during the earlier 1979 efforts by Rapu and Gill, and subsequent field seasons, as described in the Introduction (Chapter 1) of this book (see Gill, this volume). Gill collected or supervised discrete data collection, and data were entirely rechecked on a subsequent 2002 field trip to Easter Island. All records are on file at the University of Wyoming Human Remains Repository (HRR) at the University of Wyoming, Laramie. For this study, only those remains sufficiently preserved to allow collection of discrete cranial traits, and with clear provenience are used. Also, those of unknown age at death beyond childhood are excluded. This yields a total of 106 specimens. Specimens represent the five regions of the island used for this and prior studies. These regions are North, South, Northeast, West, and Southwest (Figure 7.1).
The composition of interstellar matter is driven by environmental parameters and results from extreme interstellar medium physico-chemical conditions. Astrochemists must rely on remote observations to monitor and analyze the interstellar solids composition. They bring additional information from the study of analogues produced in the laboratory, placed in simulated space environments. Planetologists and cosmochemists access and spectroscopically examine collected extraterrestrial material in the laboratory. Diffuse interstellar medium and molecular clouds observations set constraints on the composition of organic solids that can then be compared with collected extraterrestrial materials analyses, to shed light on their possible links.
This article undertakes an empirical investigation of the determinants of voluntary adoption of the ISO 14001 environmental management system by French farmers. The adoption model incorporates the expected profitability of implementing the standard and investigates the impact of prior knowledge on the probability of adopting. Two information measures are considered: a “reported information” indicator and an “estimated knowledge” score. The probit parameter estimates reveal that, while the expected profitability of implementing the standard is a significant determinant of adoption, real and perceived prior knowledge measures play a significant but potentially counterintuitive role.
Alterations of the glucocorticoid system and of hippocampal volumes have consistently been reported in patients with major depressive disorders (MDD). The aim of the present study was to investigate whether the messenger RNA (mRNA) expression of glucocorticoid inducible genes is associated with changes in the cornu ammonis (CA) and dentate gyrus subfields. Forty-three patients with MDD and 43 healthy controls were recruited and investigated with high resolution magnetic resonance imaging. Hippocampal subfields were measured using freesurfer. Measurement of whole blood mRNA expression of glucocorticoid inducible genes serum and glucocorticoid-regulated kinase 1 (SGK1), FK506 binding protein 5 (FKBP5), and glucocorticoid induced leucine zipper (GILZ) was performed. Patients with MDD had significantly smaller volumes of CA1, CA2/3, CA4/DG, and subiculum compared to healthy controls. In the regression analysis, the factor diagnosis had a significant moderating effect on the association of SGK1 and hippocampal volumes. Patients with low expression of SGK1 had significantly smaller CA2/3 and CA4/DG volumes compared to patients with high expression of SGK1 mRNA and to healthy controls with low/high expression of SGK1, respectively. Therefore, a lack of mRNA expression of glucocorticoid inducible genes in patients with MDD that seems to correspond to a blunted cortisol response is associated with smaller hippocampal CA and dentate gyrus volumes. SGK1 seems to be particularly relevant for stress-related mental disorders.
In this work, we study the acceleration of hot plasma to relativistic speed through the Compton rocket effect which is viable in the two-flow paradigm.