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Treatment for major depressive disorder (MDD) is imprecise and often involves trial-and-error to determine the most effective approach. To facilitate optimal treatment selection and inform timely adjustment, the current study investigated whether neurocognitive variables could predict an antidepressant response in a treatment-specific manner.
In the two-stage Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) trial, outpatients with non-psychotic recurrent MDD were first randomized to an 8-week course of sertraline selective serotonin reuptake inhibitor or placebo. Behavioral measures of reward responsiveness, cognitive control, verbal fluency, psychomotor, and cognitive processing speeds were collected at baseline and week 1. Treatment responders then continued on another 8-week course of the same medication, whereas non-responders to sertraline or placebo were crossed-over under double-blinded conditions to bupropion noradrenaline/dopamine reuptake inhibitor or sertraline, respectively. Hamilton Rating for Depression scores were also assessed at baseline, weeks 8, and 16.
Greater improvements in psychomotor and cognitive processing speeds within the first week, as well as better pretreatment performance in these domains, were specifically associated with higher likelihood of response to placebo. Moreover, better reward responsiveness, poorer cognitive control and greater verbal fluency were associated with greater likelihood of response to bupropion in patients who previously failed to respond to sertraline.
These exploratory results warrant further scrutiny, but demonstrate that quick and non-invasive behavioral tests may have substantial clinical value in predicting antidepressant treatment response.
Postprandial glycaemia and insulinaemia are important risk factors for type 2 diabetes. The prevalence of insulin resistance in adolescents is increasing, but it is unknown how adolescent participant characteristics such as BMI, waist circumference, fitness and maturity offset may explain responses to a standard meal. The aim of the present study was to examine how such participant characteristics affect the postprandial glycaemic and insulinaemic responses to an ecologically valid mixed meal. Data from the control trials of three separate randomised, crossover experiments were pooled, resulting in a total of 108 participants (fifty-two boys, fifty-six girls; aged 12·5 (SD 0·6) years; BMI 19·05 (SD 2·66) kg/m2). A fasting blood sample was taken for the calculation of fasting insulin resistance, using the homoeostatic model assessment of insulin resistance (HOMA-IR). Further capillary blood samples were taken before and 30, 60 and 120 min after a standardised lunch, providing 1·5 g/kg body mass of carbohydrate, for the quantification of blood glucose and plasma insulin total AUC (tAUC). Hierarchical multiple linear regression demonstrated significant predictors for plasma insulin tAUC were waist circumference, physical fitness and HOMA-IR (F(3,98) = 36·78, P < 0·001, adjusted R2 = 0·515). The variance in blood glucose tAUC was not significantly explained by the predictors used (F(7,94) = 1·44, P = 0·198). Significant predictors for HOMA-IR were BMI and maturity offset (F(2,102) = 14·06, P < 0·001, adjusted R2 = 0·021). In summary, the key findings of the study are that waist circumference, followed by physical fitness, best explained the insulinaemic response to an ecologically valid standardised meal in adolescents. This has important behavioural consequences because these variables can be modified.
Health-related fear is a normal and common response in the face of the global pandemic of COVID-19. Children and young people are frequently being exposed to messages about the threat to health, including from the media and authorities. Whilst for most, their anxiety will be proportionate to the threat, for some, existing pre-occupation with physical symptoms and illness will become more problematic. There is a growing body of evidence that health anxiety may occur in childhood, however much of the literature is taken from research using adult samples. This practitioner review aims to give an overview of the assessment and treatment of health-related worries in children and young people in the context of the COVID-19 pandemic. This review is based on the limited existing evidence in this population and the more substantial evidence base for treating health anxiety in adults. We consider the adaptations needed to ensure such interventions are developmentally appropriate.
During the last 20 years there has been increased focus on the problem of premature mortality among people with schizophrenia. This has resulted in a focus on weight gain, the development of metabolic problems, the need to understand the mechanisms behind these and the need to identify strategies to manage these problems. Audit programmes have highlighted the poor quality of monitoring for, and management of, physical health problems in people with all types of mental health disorder but particularly for those with psychotic illnesses. Further, weight gain also reinforces service users’ negative views of themselves and may lead to poor adherence with treatment (Faulkner et al., 2007; Lester et al., 2011; Weiden et al., 2004).
Emerging research suggests that maternal immune activation (MIA) may be associated with an increased risk of adverse neurodevelopmental and mental health outcomes in offspring. Using data from the Raine Study, we investigated whether MIA during pregnancy was associated with increased behavioral and emotional problems in offspring longitudinally across development.
Mothers (Generation 1; N = 1905) were classified into the following categories: AAAE (Asthma/Allergy/Atopy/Eczema; N = 1267); infection (during pregnancy; N = 1082); no AAAE or infection (N = 301). The Child Behavior Checklist (CBCL) was administered for offspring at ages 5, 8, 10, 14, and 17. Generalized estimating equations were used to investigate the effect of maternal immune status on CBCL scores.
AAAE conditions were associated with significant increases in CBCL Total (β 2.49; CI 1.98–3.00), Externalizing (β 1.54; CI 1.05–2.03), and Internalizing (β 2.28; CI 1.80–2.76) scores. Infection conditions were also associated with increased Total (β 1.27; CI 0.77–1.78), Externalizing (β 1.18; CI 0.70–1.66), and Internalizing (β 0.76; CI 0.28–1.24) scores. Exposure to more than one AAAE and/or infection condition was associated with a greater elevation in CBCL scores than single exposures in males and females. Females showed greater increases on the Internalizing scale from MIA, while males showed similar increases on both Internalizing and Externalizing scales.
MIA was associated with increased behavioral and emotional problems in offspring throughout childhood and adolescence. This highlights the need to understand the relationship between MIA, fetal development, and long-term outcomes, with the potential to advance early identification and intervention strategies.
The project described here uses an international psychiatric classification (in this case Chapter V(F) of the ICD-10 produced by the World Health Organization) as a means of international communication and educational discussion about everyday clinical issues. In a first stage, psychiatrists in Central Asian countries (Kazakhstan, Kyrgyzstan, Tajikistan and Uzbekistan) wrote 20 detailed clinical case histories about patients who suffered from disorders of the main sections of Chapter V of the ICD-10. In the second stage these were then sent to diagnostic assessment in the Eastern European countries of Ukraine, Belarus, Georgia and Russia and the West European countries of Denmark, Switzerland, German and the UK, who made independent diagnostic and clinical assessments. In the third stage all the information collected was sent to five sets of commentators who wrote a brief commentary on the similarities and difference in diagnoses and treatment, the main points can be learned from the discussion of these case histories.
Psychiatrists in central Asia, Eastern European countries and Western European countries reached similar diagnoses on the basis of case histories presented to them. There were however differences in treatment proposed as well as in the assessment of prognoses.
The use of casebooks as an educational tool to introduce a new classification or to improve its use will be discussed.
This paper summarizes several issues related to the mental health aspects of the International Classification of Impairments, Disabilities, and Handicaps (ICIDH) and its use in the field of rehabilitation. Rehabilitation is characterized by multiple interventions, demanding extensive communication and coordination among different care providers. The ICIDH will be useful in the field of rehabilitation by providing a sound framework for consequences of diseases or disorders if clear descriptions and assessment guidelines of the categories are given. The development of dedicated assessment instruments linked to the ICIDH will be useful to many health workers to assess the needs of the patients, to evaluate services and to measure the outcomes of rehabilitation interventions, thus creating a common language for disablements.
Family caregivers of people with dementia can experience loss and grief before death. We hypothesized that modifiable factors indicating preparation for end of life are associated with lower pre-death grief in caregivers.
Caregivers of people with dementia living at home or in a care home.
In total, 150 caregivers, 77% female, mean age 63.0 (SD = 12.1). Participants cared for people with mild (25%), moderate (43%), or severe dementia (32%).
Primary outcome: Marwit-Meuser Caregiver Grief Inventory Short Form (MMCGI-SF). We included five factors reflecting preparation for end of life: (1) knowledge of dementia, (2) social support, (3) feeling supported by healthcare providers, (4) formalized end of life documents, and (5) end-of-life discussions with the person with dementia. We used multiple regression to assess associations between pre-death grief and preparation for end of life while controlling for confounders. We repeated this analysis with MMCGI-SF subscales (“personal sacrifice burden”; “heartfelt sadness”; “worry and felt isolation”).
Only one hypothesized factor (reduced social support) was strongly associated with higher grief intensity along with the confounders of female gender, spouse, or adult child relationship type and reduced relationship closeness. In exploratory analyses of MMCGI-SF subscales, one additional hypothesized factor was statistically significant; higher dementia knowledge was associated with lower “heartfelt sadness.”
We found limited support for our hypothesis. Future research may benefit from exploring strategies for enhancing caregivers’ social support and networks as well as the effectiveness of educational interventions about the progression of dementia (ClinicalTrials.gov ID: NCT03332979).
Rodent models of schizophrenia (SCZ) are indispensable when screening for novel treatments, but quantifying their translational relevance with the underlying human pathophysiology has proved difficult. A novel systems methodology (shown in Figure 1) was developed integrating and comparing proteomic data of anterior prefrontal cortex tissue from SCZ post-mortem brains and matched controls with data obtained from four established glutamatergic rodent models, with the aim of evaluating which of these models represent SCZ most closely. Liquid chromatography coupled tandem mass spectrometry (LC-MSE) proteomic profiling was applied comparing healthy and “disease state” in human post-mortem samples and rodent brain tissue samples. Protein-protein interaction networks were constructed from significant abundance changes and enrichment analyses enabled the identification of pathophysiological characteristics of the disorder, which were represented across all four rodent models. Subsequently, these functional domains were used for cross-species comparisons. Five functional domains such as “development and differentiation” represented across all four rodent models, were identified. It was quantified that the chronic phencyclidine (cPCP) model represented SCZ brain changes most closely for four of these functional domains, by using machine-learning techniques. This is the first study aiming to quantify which rodent model recapitulates the neuropathological features of SCZ most closely. The methodology and findings presented here support recent efforts to overcome translational hurdles of preclinical psychiatric research by associating behavioural endophenotypes with distinct biological processes.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
In New York City, a multi-disciplinary Mass Casualty Consultation team is proposed to support prioritization of patients for coordinated inter-facility transfer after a large-scale mass casualty event. This study examines factors that influence consultation team prioritization decisions.
As part of a multi-hospital functional exercise, 2 teams prioritized the same set of 69 patient profiles. Prioritization decisions were compared between teams. Agreement between teams was assessed based on patient profile demographics and injury severity. An investigator interviewed team leaders to determine reasons for discordant transfer decisions.
The 2 teams differed significantly in the total number of transfers recommended (49 vs 36; P = 0.003). However, there was substantial agreement when recommending transfer to burn centers, with 85.5% agreement and inter-rater reliability of 0.67 (confidence interval: 0.49–0.85). There was better agreement for patients with a higher acuity of injuries. Based on interviews, the most common reason for discordance was insider knowledge of the local community hospital and its capabilities.
A multi-disciplinary Mass Casualty Consultation team was able to rapidly prioritize patients for coordinated secondary transfer using limited clinical information. Training for consultation teams should emphasize guidelines for transfer based on existing services at sending and receiving hospitals, as knowledge of local community hospital capabilities influence physician decision-making.
The shape gradient is a local sensitivity function defined on the surface of an object which provides the change in a characteristic quantity, or figure of merit, associated with a perturbation to the shape of the object. The shape gradient can be used for gradient-based optimization, sensitivity analysis and tolerance calculations. However, it is generally expensive to compute from finite-difference derivatives for shapes that are described by many parameters, as is the case for typical stellarator geometry. In an accompanying work (Antonsen, Paul & Landreman J. Plasma Phys., vol. 85 (2), 2019), generalized self-adjointness relations are obtained for magnetohydrodynamic (MHD) equilibria. These describe the relation between perturbed equilibria due to changes in the rotational transform or toroidal current profiles, displacements of the plasma boundary, modifications of currents in the vacuum region or the addition of bulk forces. These are applied to efficiently compute the shape gradient of functions of MHD equilibria with an adjoint approach. In this way, the shape derivative with respect to any perturbation applied to the plasma boundary or coil shapes can be computed with only one additional MHD equilibrium solution. We demonstrate that this approach is applicable for several figures of merit of interest for stellarator configuration optimization: the magnetic well, the magnetic ripple on axis, the departure from quasisymmetry, the effective ripple in the low-collisionality
(Nemov et al.Phys. Plasmas, vol. 6 (12), 1999, pp. 4622–4632) and several finite-collisionality neoclassical quantities. Numerical verification of this method is demonstrated for the magnetic well figure of merit with the VMEC code (Hirshman & Whitson Phys. Fluids, vol. 26 (12), 1983, p. 3553) and for the magnetic ripple with modification of the ANIMEC code (Cooper et al.Comput. Phys. Commun., vol. 72 (1), 1992, pp. 1–13). Comparisons with the direct approach demonstrate that, in order to obtain agreement within several per cent, the adjoint approach provides a factor of
in computational savings.
Declining species richness is a global concern; however, the coarse-scale metrics used at regional or landscape levels might not accurately represent the important habitat characteristics needed to estimate species richness. Currently, there exists a lack of knowledge with regard to the spatial extent necessary to correlate remotely sensed habitat metrics to species richness and animal surveys. We provide a protocol for determining the best scale to use when merging remotely sensed habitat and animal survey data as a step towards improving estimates of vertebrate species richness on broad scales. We test the relative importance of fine-resolution habitat heterogeneity and productivity metrics at multiple spatial scales as predictors of species richness for birds, frogs and mammals using a Bayesian approach and a combination of passive monitoring technologies. Model performance was different for each taxonomic group and dependent on the scale at which habitat heterogeneity and productivity were measured. Optimal scales included a 20-m radius for bats and frogs, an 80-m radius for birds and a 180-m radius for terrestrial mammals. Our results indicate that optimal scales do exist when merging remotely sensed habitat measures with ground-based surveys, but they differ between vertebrate groups. Additionally, the selection of a measurement scale is highly influential to our understanding of the relationships between species richness and habitat characteristics.
Non-tuberculous mycobacterium encephalitis is rare. Since 2013, a global outbreak of Mycobacterium chimaera infection has been attributed to point-source contamination of heater cooler units used in cardiac surgery. Disseminated M. chimaera infection has presented many unique challenges, including non-specific clinical presentations with delays in diagnosis, and a high mortality rate among predominantly immunocompetent adults. Here, we describe three patients with fatal disseminated Mycobacterium chimaera infection showing initially non-specific, progressively worsening neurocognitive decline, including confusion, delirium, depression and apathy. Autopsy revealed widespread granulomatous encephalitis of the cerebrum, brain stem and spinal cord, along with granulomatous chorioretinitis. Cerebral involvement and differentiation between mycobacterial granulomas and microangiopathic changes can be assessed best on MRI with contrast enhancement. The prognosis of M. chimaera encephalitis appears to be very poor, but might be improved by increased awareness of this new syndrome and timely antimicrobial treatment.
This presentation will enable the learner to:
1.Describe the clinical, radiological and neuropathological findings of Mycobacterium chimaera encephalitis
2.Be aware of this rare form of encephalitis, and explain its diagnosis, prognosis and management
We present a broad study of linear, clustered, noble gas puffs irradiated with the frequency doubled (527 nm) Titan laser at Lawrence Livermore National Laboratory. Pure Ar, Kr, and Xe clustered gas puffs, as well as two mixed-gas puffs consisting of KrAr and XeKrAr gases, make up the targets. Characterization experiments to determine gas-puff density show that varying the experimental parameter gas-delay timing (the delay between gas puff initialization and laser-gas-puff interaction) provides a simple control over the gas-puff density. X-ray emission (>1.4 keV) is studied as a function of gas composition, density, and delay timing. Xe gas puffs produce the strongest peak radiation in the several keV spectral region. The emitted radiation was found to be anisotropic, with smaller X-ray flux observed in the direction perpendicular to both laser beam propagation and polarization directions. The degree of anisotropy is independent of gas target type but increases with photon energy. X-ray spectroscopic measurements estimate plasma parameters and highlight their difference with previous studies. Electron beams with energy in excess of 72 keV are present in the noble gas-puff plasmas and results indicate that Ar plays a key role in their production. A drastic increase in harder X-ray emissions (X-ray flash effect) and multi-MeV electron-beam generation from Xe gas-puff plasma occurred when the laser beam was focused on the front edge of the linear gas puff.
Despite considerable academic attention to the role of family caregivers within the general population, little research has been conducted with Indigenous families. This qualitative study aims to fill that gap by focusing on the experiences of Metis caregivers providing care for older Metis adults. Focus groups and interviews were conducted with Metis family caregivers (n = 79), Metis Elders (n = 11) and formal caregivers (n = 8). Although there are considerable parallels in the caregiving experiences identified in this Metis study with those already documented in the literature, there are nonetheless important differences for providing culturally responsive care to Metis seniors.
Concerns have repeatedly been expressed about the quality of physical healthcare that people with psychosis receive.
To examine whether the introduction of a financial incentive for secondary care services led to improvements in the quality of physical healthcare for people with psychosis.
Longitudinal data were collected over an 8-year period on the quality of physical healthcare that people with psychosis received from 56 trusts in England before and after the introduction of the financial incentive. Control data were also collected from six health boards in Wales where a financial incentive was not introduced. We calculated the proportion of patients whose clinical records indicated that they had been screened for seven key aspects of physical health and whether they were offered interventions for problems identified during screening.
Data from 17 947 people collected prior to (2011 and 2013) and following (2017) the introduction of the financial incentive in 2014 showed that the proportion of patients who received high-quality physical healthcare in England rose from 12.85% to 31.65% (difference 18.80, 95% CI 17.37–20.21). The proportion of patients who received high-quality physical healthcare in Wales during this period rose from 8.40% to 13.96% (difference 5.56, 95% CI 1.33–10.10).
The results of this study suggest that financial incentives for secondary care mental health services are associated with marked improvements in the quality of care that patients receive. Further research is needed to examine their impact on aspects of care that are not incentivised.
This research article addresses an important issue related to how teachers can support Aboriginal secondary school students' learning of science. Drawn from a larger project that investigated the study of vertebrates using Queensland Indigenous knowledges and Montessori Linnaean materials to engage Indigenous secondary school students, this article focuses on the three-staged lessons from that study. Using an Action Research approach and working with participants from one secondary high school in regional Queensland with a high Indigenous population, there were several important findings. First, the materials and the three-staged lessons generated interest in learning Eurocentric science knowledge. Second, repetition, freedom and unhurried inclusion of foreign science knowledges strengthened students' Aboriginal personal identity as well as identities as science learners. Third, privileging of local Aboriginal knowledge and animal language gave rise to meaningful and contextualised Linnaean lessons and culturally responsive practices.