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Critical components of 'Early Intervention in Psychosis': national retrospective cohort study.
BACKGROUND: Psychotic disorders are severe mental health conditions frequently associated with long-term disability, reduced quality of life and premature mortality. Early Intervention in Psychosis (EIP) services aim to provide timely, comprehensive packages of care for people with psychotic disorders. However, it is not clear which components of EIP services contribute most to the improved outcomes they achieve. AIMS: We aimed to identify associations between specific components of EIP care and clinically significant outcomes for individuals treated for early psychosis in England. METHOD: This national retrospective cohort study of 14 874 EIP individuals examined associations between 12 components of EIP care and outcomes over a 3-year follow-up period, by linking data from the National Clinical Audit of Psychosis (NCAP) to routine health outcome data held by NHS England. The primary outcome was time to relapse, defined as psychiatric inpatient admission or referral to a crisis resolution (home treatment) team. Secondary outcomes included duration of admissions, detention under the Mental Health Act, emergency department and general hospital attendances and mortality. We conducted multilevel regression analyses incorporating demographic and service-level covariates. RESULTS: Smaller care coordinator case-loads and the use of clozapine for eligible people were associated with reduced relapse risk. Physical health interventions were associated with reductions in mortality risk. Other components, such as cognitive-behavioural therapy for psychosis (CBTp), showed associations with improvements in secondary outcomes. CONCLUSIONS: Smaller case-loads should be prioritised and protected in EIP service design and delivery. Initiatives to improve the uptake of clozapine should be integrated into EIP care. Other components, such as CBTp and physical health interventions, may have specific benefits for those eligible. These findings highlight impactful components of care and should guide resource allocation to optimise EIP service delivery.
Supporting people in Early Intervention in Psychosis services: the role of primary care.
BACKGROUND: Early Intervention in Psychosis (EIP) services offer treatment to people experiencing a first episode of psychosis. Service users may be referred from primary care and discharged directly back at the end of their time in an EIP service. AIM: To explore the role of primary care in supporting EIP service users (SUs) and to understand how to improve collaboration between primary and specialist care. METHOD: Qualitative study comprising semi-structured interviews with SUs, carers, healthcare professionals (HCPs), managers, and commissioners. Interviews were conducted either online or by telephone. Thematic analysis was carried out using principles of constant comparison. Patient and public involvement were key to all stages, including data analysis. RESULTS: In total, 55 interviews were conducted with SUs (n = 13), carers (n = 10), and GPs, EIP HCPs, managers, and commissioners (n = 33). GPs reported difficulties in referring people into EIP services and little contact with SUs while in EIP services, even about physical health. GPs suggested they were not included in planning discharge from EIP to primary care. SUs and carers reported that transition from EIP can lead to uncertainty, distress, and exacerbation of symptoms. GPs reported only being made aware of patients on or after discharge, with no contact for 3 years. GPs described difficulty managing complex medication regimes, and barriers to re-referral to mental health services. CONCLUSION: GPs have a key role in supporting people within EIP services, specifically monitoring and managing physical health. Inclusion of GPs in planning discharge from EIP services is vital.
Cost-effectiveness of therapist-assisted internet-delivered psychological therapies for PTSD differing in trauma focus in England: an economic evaluation based on the STOP-PTSD trial.
BACKGROUND: Although there are effective psychological treatments for post-traumatic stress disorder (PTSD), they remain inaccessible for many people. Digitally enabled therapy is a way to overcome this problem; however, there is little evidence on which forms of these therapies are most cost effective in PTSD. We aimed to assess the cost-effectiveness of the STOP-PTSD trial, which evaluated two therapist-assisted, internet-delivered cognitive behavioural therapies: cognitive therapy for PTSD (iCT-PTSD) and a programme focusing on stress management (iStress-PTSD). METHODS: In this health economic evaluation, we used data from the STOP-PTSD trial (n=217), a single-blind, randomised controlled trial, to compare iCT-PTSD and iStress-PTSD in terms of resource use and health outcomes. In the trial, participants (aged ≥18 years) who met DSM-5 criteria for PTSD were recruited from primary care therapy services in South East England. The interventions were delivered online with therapist support for the first 12 weeks, and three telephone calls over the next 3 months. Participants completed questionnaires on symptoms, wellbeing, quality of life, and resource use at baseline, 13 weeks, 26 weeks, and 39 weeks after randomisation. We used a cost-effectiveness analysis to assess cost per quality-adjusted life year (QALY) at 39 weeks post-randomisation, from the perspective of the English National Health Service (NHS) and personal social services and on the basis of intention-to-treat for complete cases. Treatment modules and the platform design were developed with extensive input from service users: service users also advised on the trial protocol and methods, including the health economic measures. This is a pre-planned analysis of the STOP-PTSD trial; the trial was registered prospectively on the ISRCTN Registry (ISRCTN16806208). FINDINGS: NHS costs were similar across treatment groups, but clinical outcomes were superior for iCT-PTSD compared with iStress-PTSD. The incremental cost-effectiveness ratio for NHS costs and personal social services was estimated as £1921 per QALY. iCT-PTSD had an estimated 91·6% chance of being cost effective at the £20 000 per QALY threshold. From the societal perspective, iCT-PTSD was cost saving compared with iStress-PTSD. INTERPRETATION: iCT-PTSD is a cost-effective form of therapist-assisted, internet-delivered psychological therapy relative to iStress-PTSD, and it could be considered for clinical implementation. FUNDING: Wellcome Trust and National Institute of Health Research Oxford Health Biomedical Research Centre.
Precision computerised cognitive behavioural therapy (cCBT) intervention for adolescents with depression (SPARX-UK): protocol for the process evaluation of a pilot randomised controlled feasibility trial.
INTRODUCTION: While digital technologies can increase the availability and access to evidence-based interventions, little is known about how users engage with them and the mechanisms associated with effective outcomes. Process evaluations are an important component in understanding the aforementioned factors. The 'SPARX-UK' study is a randomised controlled pilot and feasibility trial evaluating personalised human-supported (from an 'eCoach') vs a self-directed computerised cognitive behavioural therapy intervention (cCBT), called SPARX (Smart, Positive, Active, Realistic, X-factor thoughts), aimed at adolescents with mild to moderate depression. We are comparing supported vs self-directed delivery of SPARX to establish which format should be used in a proposed definitive trial of SPARX. The control is a waitlist group. We will conduct a process evaluation alongside the trial to determine how the intervention is implemented and provide context for interpreting the feasibility trial outcomes. We will also look at the acceptability of SPARX and how users engage with the intervention. This protocol paper describes the rationale, aims and methodology of the SPARX-UK trial process evaluation. METHODS AND ANALYSIS: The process evaluation will use a mixed-methods design following the UK Medical Research Council's 2015 guidelines, comprising quantitative and qualitative data collection. This will include analysing data usage of participants in the intervention arms; purposively sampled, semi-structured interviews of adolescents, parents/guardians, eCoaches and clinicians/practitioners from the SPARX-UK trial; and analysis of qualitative comments from a survey from those who dropped out early from the trial. Quantitative data will be analysed descriptively. We will use thematic analysis in a framework approach to analyse qualitative data. Quantitative and qualitative data will be mixed and integrated to provide an understanding of how the intervention was implemented and how adolescents interacted with the intervention. This process evaluation will explore the experiences of adolescent participants, parents/guardians, eCoaches and clinicians/practitioners in relation to a complex digital intervention. ETHICS: Ethical approval was granted by the National Health Service (NHS) Health Research Authority South West - Cornwall & Plymouth Research Ethics Committee (Ethics Ref: 22/SW/0149). DISSEMINATION: Contextualising how the intervention was implemented, and the variations in uptake and engagement, will help us to understand the trial findings in greater depth. The findings from this process evaluation will also inform the decision about whether and how to proceed with a full randomised controlled trial, as well as the development of more effective interventions which can be personalised more precisely via varying levels of human support. We plan to publish the findings of the process evaluation and the wider project in peer-reviewed journals, as well as disseminate via academic conferences. TRIAL REGISTRATION NUMBER: ISRCTN: ISRCTN15124804. Registered on 16 January 2023, https://www.isrctn.com/ISRCTN15124804.
Risk assessment tools used at the policing stage for health and crime outcomes: A systematic review and meta-analysis.
INTRODUCTION: Risk assessment tools are increasingly employed at the policing stage to consider health-related needs and predict crime outcomes such as repeat intimate partner violence (IPV). Decisions informed by these tools can influence health outcomes, disproportionately affecting certain groups and potentially exacerbating health inequalities. However, their predictive accuracy, quality, and reliability remain uncertain. METHODS: Following PRISMA guidelines, we conducted a systematic review of development/derivation and validation studies on risk assessment tools used at the policing stage to evaluate health and crime outcomes. RESULTS: We identified 29 studies with 256,125 participants, reporting performance measures for 28 different tools for a range of health related and crime outcomes. The most common assessment was risk of IPV (18 studies or 62 %), and three studies (10 %) considered other health-related outcomes. Pooled estimates for outcomes ranged from 0.64 to 0.73, representing poor to moderate performance. The tools for predicting IPV demonstrated the weakest performance with a pooled AUC of 0.64 (95 % CI: 0.62, 0.66). The reporting of other performance measures beyond the AUC, such as true and false positives and negatives, and calibration was inadequate. CONCLUSIONS: Current evidence for the routine use of existing risk assessment tools at the policing stage is limited. Some newer tools, developed with robust methodologies, show high predictive performance. Research should prioritize the development, validation, and implementation of these newer tools, particularly for outcomes with significant morbidity and mortality, such as IPV victimization. Implementing higher quality tools could reduce health inequalities by fostering more consistent decision-making and efficient resource allocation.
Alcohol Use and Risk of Dementia in Diverse Populations: Evidence from Cohort, Case-control and Mendelian randomization Approaches
Objectives To investigate the relationship between alcohol consumption and dementia. Design Prospective cohort and case-control analyses combined with linear and nonlinear Mendelian randomization. Setting Two large-scale population-based cohorts: the US Million Veteran Program and UK Biobank. Genetic analyses used summary statistics from genome-wide association studies (GWAS). Participants 559,559 adults aged 56–72 years at baseline were included in observational analyses (mean follow-up: 4 years in the US cohort; 12 years in the UK cohort). Genetic analyses used summary data from multiple large GWAS consortia (2.4 million participants). Main outcome measures Incident all-cause dementia, determined through health record linkage, and genetic proxies. Results During follow-up, 14,540 participants developed dementia and 48,034 died. Observational phenotype-only analyses revealed U-shaped associations between alcohol and dementia risk: higher risk was observed among non-drinkers, heavy drinkers (>40 drinks per week; hazard ratio [HR]=1.41, 95% confidence interval[CI] 1.15-1.74), and those with alcohol use disorder (AUD) (HR=1.51[CI 1.42-1.60]) compared with light drinkers. In contrast, Mendelian randomization genetic analysis identified a monotonic increase in dementia risk with greater alcohol consumption. A one standard deviation increase in log-transformed drinks per week was associated with a 15% dementia increase (IVW OR=1.15[1.03-1.27]). A two-fold increase in AUD prevalence was associated with a 16% increase in dementia risk (inverse-variance weighted [IVW] OR=1.16[1.03-1.30]). Alcohol intake increased dementia, but individuals who developed dementia also experienced a decline in alcohol intake over time, suggesting reverse causation—where early cognitive decline leads to reduced alcohol consumption— underlies the supposed protective alcohol effects in observational studies. Conclusions These findings provide evidence for a relationship between all types of alcohol use and increased dementia risk. While correlational observational data suggested a protective effect of light drinking, this could be in part attributable to reduced drinking seen in early dementia; genetic analyses did not support this, suggesting that any level of alcohol consumption may contribute to dementia risk. Public health strategies that reduce the prevalence of alcohol use disorder could potentially lower the incidence of dementia by up to 16%.
Changes in sensorimotor network dynamics in resting-state recordings in Parkinson's disease.
Non-invasive recordings of magnetoencephalography have been used for developing biomarkers for neural changes associated with Parkinson's disease that can be measured across the entire course of the disease. These studies, however, have yielded inconsistent findings. Here, we investigated whether analysing motor cortical activity within the context of large-scale brain network activity provides a more sensitive marker of changes in Parkinson's disease using magnetoencephalography. We extracted motor cortical beta power and beta bursts from resting-state magnetoencephalography scans of patients with Parkinson's disease (N = 28) and well-matched healthy controls (N = 36). To situate beta bursts in their brain network contexts, we used a time-delay-embedded hidden Markov model to extract brain network activity and investigated co-occurrence patterns between brain networks and beta bursts. Parkinson's disease was associated with decreased beta power in motor cortical power spectra, but no significant differences in motor cortical beta-burst dynamics occurred when using a conventional beta-burst analysis. Dynamics of a large-scale sensorimotor network extracted with the time-delay-embedded hidden Markov model approach revealed significant decreases in the occurrence of this network with Parkinson's disease. By comparing conventional burst and time-delay-embedded hidden Markov model state occurrences, we observed that motor beta bursts occurred during both sensorimotor and non-sensorimotor network activations. When using the large-scale network information provided by the time-delay-embedded hidden Markov model to focus on bursts that were active during sensorimotor network activations, significant decreases in burst dynamics could be observed in patients with Parkinson's disease. In conclusion, our findings suggest that decreased motor cortical beta power in Parkinson's disease is prominently associated with changes in sensorimotor network dynamics using magnetoencephalography. Thus, investigating large-scale networks or considering the large-scale network context of motor cortical activations may be crucial for identifying alterations in the sensorimotor network that are prevalent in Parkinson's disease and might help resolve contradicting findings in the literature.
Navigating Discharge From Early Intervention in Psychosis Services: A Qualitative Exploration of the Experiences of Service Users and Carers.
INTRODUCTION: Early Intervention in Psychosis (EIP) services in England offer up to 3 years' time-limited support to people experiencing early psychosis. Service users (SUs) are discharged to primary care, a community mental health team (CMHT), or other specialist mental health service. The aim of this study is to explore the SU and carer journey through discharge from EIP and into the early post-discharge period. METHODS: Qualitative longitudinal study comprising semi-structured interviews with SUs and carers at, or shortly after, discharge from EIP, and follow-up interviews with SUs 6-11 months later. Data collection conducted between January 2023-September 2024 and informed by information power. Data were thematically analysed by a multidisciplinary team. RESULTS: SUs and carers expressed their desire to be actively involved in EIP discharge planning and decision-making. They contrasted close relationships with EIP practitioners with inaccessibility of care and difficulties navigating healthcare systems after discharge. Some SUs described feelings of abandonment and expressed a wish for transitional support, and proactive, relationship-based care post-discharge. Carers played an important role as patient advocates but were rarely offered support themselves. CONCLUSION: Improved collaboration is needed between SUs, carers and primary care/CMHT practitioners in the build-up to EIP discharge. There should be proactive contact from primary care at the point of discharge and in the early post-discharge period. Carer needs are often overlooked; primary care could utilise the 'carers register' and proactively offer support. PATIENT OR PUBLIC CONTRIBUTION: Patient and carer involvement and engagement was key to all stages of this study. The research team met regularly with our two co-investigators with lived experience (as a service user and a carer), who contributed to data analysis and writing this paper. We worked closely with our patient and carer advisory group, EXTEND-ing, throughout the research process. They helped formulate research questions, co-designed topic guides and participant information sheets, and contributed to data analysis and interpretation.
Racialised experience of detention under the Mental Health Act: a photovoice investigation.
BACKGROUND: The rates of compulsory admission and treatment (CAT) are rising in mental health systems in the UK. Persistent disparities have been reported among migrants, and black and ethnic minorities in Europe and North America for decades. Lived experience data can provide novel insights to reduce coercive care. METHODS: We purposively sampled people within 2 years of receiving CAT, to maximise diversity by age, sex, ethnicity and different 'sections' of the Mental Health Act (England and Wales) from eight health systems in England. Using participatory photovoice workshops, we assembled images, captions and reflective narratives, which were transcribed and subjected to thematic and intersectional analyses. The interpretation privileged lived experiences of participants and peer researchers alongside the research team. Preventive insights informed a logic model to reduce CAT. RESULTS: Forty-eight ethnically diverse people contributed over 500 images and 30 hours of recorded narratives. A significant proportion of participants reported multimorbidity, adverse childhood experiences and carer roles. Their experiences indicated insufficient co-ordination to prevent CAT despite early help seeking; they were not taken seriously or believed when seeking help. Dismissive responses and even hostility from professionals and unnecessary police involvement were distressing, stigmatising and risked criminalisation. Participants wanted more (a) advocacy given in crisis, (b) trauma-informed therapeutic and creative support from inpatient into community settings, (c) family and carer involvement and (d) more information about how to negotiate care options, appeals, restriction and seclusion. Practitioners were felt to lack the essential skills to care for racialised and traumatised people subjected to CAT. CONCLUSIONS: We propose a lived experience logic model for the practice, policy and legislative solutions to reduce epistemic injustice, CAT and criminalising care.
Paired plasma lipidomics and proteomics analysis in the conversion from mild cognitive impairment to Alzheimer's disease.
BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative condition for which there is currently no available medication that can stop its progression. Previous studies suggest that mild cognitive impairment (MCI) is a phase that precedes the disease. Therefore, a better understanding of the molecular mechanisms behind MCI conversion to AD is needed. METHOD: Here, we propose a machine learning-based approach to detect the key metabolites and proteins involved in MCI progression to AD using data from the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery Study. Proteins and metabolites were evaluated separately in multiclass models (controls, MCI and AD) and together in MCI conversion models (MCI stable vs converter). Only features selected as relevant by 3/4 algorithms proposed were kept for downstream analysis. RESULTS: Multiclass models of metabolites highlighted nine features further validated in an independent cohort (0.726 mean balanced accuracy). Among these features, one metabolite, oleamide, was selected by all the algorithms. Further in-vitro experiments in rodents showed that disease-associated microglia excreted oleamide in vesicles. Multiclass models of proteins stood out with nine features, validated in an independent cohort (0.720 mean balanced accuracy). However, none of the proteins was selected by all the algorithms. Besides, to distinguish between MCI stable and converters, 14 key features were selected (0.872 AUC), including tTau, alpha-synuclein (SNCA), junctophilin-3 (JPH3), properdin (CFP) and peptidase inhibitor 15 (PI15) among others. CONCLUSIONS: This omics integration approach highlighted a set of molecules associated with MCI conversion important in neuronal and glia inflammation pathways.
Longitudinal changes in striatocortical connectivity in first-episode psychosis associated with the emergence of treatment resistance.
Treatment resistance affects up to one in four individuals with psychosis in the first few years of illness. However, there is limited information about the brain changes associated with treatment resistance, restricting our ability to develop effective prognostic biomarkers or new treatments. Using resting-state functional MRI, we examined striatocortical connectivity in 87 patients who presented a non-affective first-episode of psychosis and 118 healthy controls, with follow-up imaging on more than half of the participants in the next 6 years, totaling 361 images. Crucially, we identified 30 patients who presented treatment-resistant psychosis in this follow-up period. Thus, we examined baseline (at first episode) and longitudinal striatocortical differences within psychosis subgroups (treatment-responsive and treatment-resistant psychosis), and between patients subgroups and healthy controls. Compared to healthy controls, participants with treatment-responsive psychosis presented baseline differences in functional connectivity of ventral striatal systems, without changes over time; whereas patients with treatment-resistant psychosis showed both baseline and longitudinal differences in ventral striatal systems, compared to healthy controls. Treatment-responsive and treatment-resistant psychosis groups differed in longitudinal changes in connectivity between ventral striatal and temporal cortical regions. This is one of the circuits which has been previously related to symptom improvements in patients with first-episode of psychosis. No baseline differences were observed between the two psychosis groups. Overall, treatment-resistant psychosis is characterized by longitudinal changes in striatal systems in early psychosis, which might be used as the basis of future prognostic biomarkers.
Quantifying long-term health and economic outcomes for survivors of group B Streptococcus invasive disease in infancy: protocol of a multi-country study in Argentina, India, Kenya, Mozambique and South Africa
Sepsis and meningitis due to invasive group B Streptococcus (iGBS) disease during early infancy is a leading cause of child mortality. Recent systematic estimates of the worldwide burden of GBS suggested that there are 319,000 cases of infant iGBS disease each year, and an estimated 147,000 stillbirths and young-infant deaths, with the highest burden occurring in Sub-Saharan Africa. The following priority data gaps were highlighted: (1) long-term outcome data after infant iGBS, including mild disability, to calculate quality-adjusted life years (QALYs) or disability-adjusted life years (DALYs) and (2) economic burden for iGBS survivors and their families. Geographic data gaps were also noted with few studies from low- and middle- income countries (LMIC), where the GBS burden is estimated to be the highest. In this paper we present the protocol for a multi-country matched cohort study designed to estimate the risk of long-term neurodevelopmental impairment (NDI), socioemotional behaviors, and economic outcomes for children who survive invasive GBS disease in Argentina, India, Kenya, Mozambique, and South Africa. Children will be identified from health demographic surveillance systems, hospital records, and among participants of previous epidemiological studies. The children will be aged between 18 months to 17 years. A tablet-based custom-designed application will be used to capture data from direct assessment of the child and interviews with the main caregiver. In addition, a parallel sub-study will prospectively measure the acute costs of hospitalization due to neonatal sepsis or meningitis, irrespective of underlying etiology. In summary, these data are necessary to characterize the consequences of iGBS disease and enable the advancement of effective strategies for survivors to reach their developmental and economic potential. In particular, our study will inform the development of a full public health value proposition on maternal GBS immunization that is being coordinated by the World Health Organization.
The relationship between isolated hypertension with brain volumes in UK Biobank.
BACKGROUND: Hypertension is a well-established risk factor for cognitive impairment, brain atrophy, and dementia. However, the relationship of other types of hypertensions, such as isolated hypertension on brain health and its comparison to systolic-diastolic hypertension (where systolic and diastolic measures are high), is still relatively unknown. Due to its increased prevalence, it is important to investigate the impact of isolated hypertension to help understand its potential impact on cognitive decline and future dementia risk. In this study, we compared a variety of global brain measures between participants with isolated hypertension to those with normal blood pressure (BP) or systolic-diastolic hypertension using the largest cohort of healthy individuals. METHODS: Using the UK Biobank cohort, we carried out a cross-sectional study using 29,775 participants (mean age 63 years, 53% female) with BP measurements and brain magnetic resonance imaging (MRI) data. We used linear regression models adjusted for multiple confounders to compare a variety of global, subcortical, and white matter brain measures. We compared participants with either isolated systolic or diastolic hypertension with normotensives and then with participants with systolic-diastolic hypertension. RESULTS: The results showed that participants with isolated systolic or diastolic hypertension taking BP medications had smaller gray matter but larger white matter microstructures and macrostructures compared to normotensives. Isolated systolic hypertensives had larger total gray matter and smaller white matter traits when comparing these regions with participants with systolic-diastolic hypertension. CONCLUSIONS: These results provide support to investigate possible preventative strategies that target isolated hypertension as well as systolic-diastolic hypertension to maintain brain health and/or reduce dementia risk earlier in life particularly in white matter regions.
Risk of repeat self-harm among individuals presenting to healthcare services: development and validation of a clinical risk assessment model (OxSET).
BACKGROUND: A self-harm episode is a major risk factor for repeat self-harm. Existing tools to assess and predict repeat self-harm have major methodological limitations, and few are externally validated. OBJECTIVE: To develop and validate a risk assessment model of repeat self-harm up to 6 months after an episode of non-fatal self-harm that resulted in an emergency visit to hospital or specialised care. METHODS: Using Swedish national registers, we identified 53 172 people aged≥10 years who self-harmed during 2008-2012. We allocated 37 523 individuals to development (2820 or 7.5% repeat self-harm incidents within 6 months) and 15 649 to geographic validation (1373 repeat episodes) samples, based on region of residence. In a temporal validation of people who self-harmed during 2018-2019, we identified 25 036 individuals (2886 repeat episodes). We fitted a multivariable accelerated failure time model to predict risk of repeat self-harm. FINDINGS: In the external validations (n=40 685), rates of repeat self-harm were 8.8%-11.5% over 6 months. The final model retained 17 factors. Calibration and discrimination were similar in both validation samples, with observed-to-expected ratio=1.15 (95% CI=1.09 to 1.21) and c-statistic=0.72 (95% CI=0.70 to 0.73) in the geographical validation. At 6 months and a 10% risk cut-off, sensitivity was 51.5% (95% CI=48.8% to 54.2%) and specificity was 80.7% (95% CI=80.1% to 81.4%) in geographic validation; corresponding values were 56.9% (95% CI=55.1% to 58.7%) and 76.0% (95% CI=75.5% to 76.6%) in temporal validation. Discrimination was slightly worse at the 1-month prediction horizon (c-statistics of 0.66-0.68). CONCLUSIONS: Using mostly routinely collected data, simple risk assessment models and tools can provide acceptable levels of accuracy for repeat of self-harm. CLINICAL IMPLICATIONS: This risk model (OXford SElf-harm repeat tool) may assist clinical decision-making.
Functional brain imaging and connectivity in dementia
Although several dierent image modalities will be described, neuroimaging studies of brain function in dementia largely fall into two categories: (1) the study of resting blood ow and (2) measurement of brain changes due to a specic task. is chapter starts with a brief description of methods of emission tomography, functional magnetic resonance imaging (fMRI) and diusion tensor imaging (DTI) before describing applications in patients.
Innate and adaptive immunity in the development of depression: An update on current knowledge and technological advances.
The inflammation theory of depression, proposed over 20years ago, was influenced by early studies on T cell responses and since then has been a stimulus for numerous research projects aimed at understanding the relationship between immune function and depression. Observational studies have shown that indicators of immunity, especially C reactive protein and proinflammatory cytokines, such as interleukin 6, are associated with an increased risk of depressive disorders, although the evidence from randomized trials remains limited and only few studies have assessed the interplay between innate and adaptive immunity in depression. In this paper, we review current knowledge on the interactions between central and peripheral innate and adaptive immune molecules and the potential role of immune-related activation of microglia, inflammasomes and indoleamine-2,3-dioxygenase in the development of depressive symptoms. We highlight how combining basic immune methods with more advanced 'omics' technologies would help us to make progress in unravelling the complex associations between altered immune function and depressive disorders, in the identification of depression-specific biomarkers and in developing immunotherapeutic treatment strategies that take individual variability into account.