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Cash transfer programmes transfer cash to low-income households or individuals to expand social protection among the most vulnerable. Changes that happen during adolescence may impact whether or not a cash transfer programme is effective in encouraging certain behaviours.
Brain and muscle chemistry in myalgic encephalitis/chronic fatigue syndrome (ME/CFS) and long COVID: a 7T magnetic resonance spectroscopy study.
Myalgic encephalitis/chronic fatigue syndrome (ME/CFS) is a common debilitating medical condition, whose main symptoms - fatigue, post-exertional malaise and cognitive dysfunction - are also present in many cases of long COVID. Magnetic resonance spectroscopy (MRS) allows the insight into their pathophysiology through exploration of a range of biochemicals putatively relevant to aetiological processes, in particular mitochondrial dysfunction and energy metabolism. 24 patients with ME/CFS, 25 patients with long COVID and 24 healthy controls (HC) underwent brain (pregenual and dorsal anterior cingulate cortex, respectively, pgACC and dACC) and calf muscle MRS scanning at 7 Tesla, followed by a computerised cognitive assessment. Compared to HC, ME/CFS patients had elevated levels of lactate in both pgACC and dACC, while long COVID patients had lowered levels of total choline in dACC. By contrast, skeletal muscle metabolites at rest did not significantly differ between the groups. The changes in lactate in ME/CFS are consistent with the presence of energetic stress and mitochondrial dysfunction. A reduction in total choline in long COVID is of interest in the context of the recently reported association between blood clots and 'brain fog', and earlier animal studies showing that choline might prevent intravascular coagulation. Importantly, differences in findings between ME/CFS and long COVID suggest that the underlying neurobiological mechanisms, while leading to similar clinical presentations, may differ. An important implication is that patients with ME/CFS and those with fatigue in the course of long COVID should not be studied as a single group, at least until the mechanisms are better understood.
Negative bias in encoding and recall memory in depressed patients with inadequate response to antidepressant medication.
RATIONALE: Cognitive theories propose that negative biases in emotional processing contribute to the maintenance of depressive states. Previous studies reported that acute antidepressant treatment in depressed patients reversed negative emotional biases. However, studies addressing the differences in emotional processing between healthy volunteers and clinically depressed patients with inadequate response to standard antidepressant treatments are limited. OBJECTIVES: To investigate the differences in emotional processing domains between depressed patients with inadequate response to current antidepressant treatment and healthy controls. METHODS: Fifty-four medicated patients with major depression and 45 age- and sex-equated healthy volunteers were tested using the Oxford Emotional Testing Battery. RESULTS: There was no difference between the two groups in the accuracy of recognising emotional facial expressions. However, there was a significant difference in the pattern of response times in an emotional categorisation task (F1,97 = 6.44, p = 0.013, partial η2 = 0.017) where healthy controls had faster responses towards positive than negative self-referent words (95%CI: -0.291 - -0.054, p = 0.005). In contrast, patients had no significant differences in reaction time for categorizing positive and negative self-referent descriptors. There was also a significant group interaction in an emotional memory task (F1,91 = 7.90, p = 0.006, partial η2 = 0.080) where healthy volunteers recalled significantly more positively valenced words than depressed patients (95%CI: -2.104 - -0.168, p = 0.022). CONCLUSIONS: Depressed patients with inadequate responses toward antidepressants had negative biases in emotional categorisation and emotional memory. These psychological abnormalities may represent targets for treatment in patients with difficult-to-treat depression.
Transdiagnostic early warning score for psychiatric hospitalisation: development and evaluation of a prediction model.
BACKGROUND: The lack of an early warning score for psychiatric hospitalisation means that the decision to initiate preventative interventions is based solely on clinical judgement, which is prone to bias. OBJECTIVE: The objective is to develop and externally validate a transdiagnostic score that predicts psychiatric hospitalisation. METHODS: In this retrospective cohort study using deidentified electronic health records from 20 healthcare organisations in the NeuroBlu Data, we identified all patients with any of seven major psychiatric disorders with at least five Clinical Global Impressions of Severity and five Global Assessment of Functioning measured over a period of 6 consecutive months before any hospitalisation. From these measurements, metrics of clinical severity and instability and functional severity and instability were derived and incorporated into a score predicting the 6-month risk of incident psychiatric hospitalisation. Discrimination and calibration of this score were validated in an external sample. The transdiagnostic validity of the score was evaluated and its performance was compared between white and non-white people. FINDINGS: Altogether, 37 049 individuals (531 incident hospitalisations) were included. The predictive model showed good discrimination in the training (optimism-adjusted c-index: 0.74, 95% CI 0.72 to 0.76) and external validation (c-index: 0.80, 95% CI 0.78 to 0.82) samples, with adequate calibration. Discrimination improved with adjustment for organisation-level hospitalisation rates (c-index: 0.80, 95% CI 0.78 to 0.82 and 0.84, 95% CI 0.82 to 0.86 in the derivation and validation samples). Good discrimination was also achieved for each diagnostic category (c-index: 0.71-0.82 and 0.64-0.75 with/without adjustment for organisation-level hospitalisation rates, respectively). There was no significant difference in model performance between white and non-white people. DISCUSSION: A transdiagnostic early warning system based on simple longitudinal measurements can reliably and robustly predict psychiatric hospitalisation. It will help target preventative interventions to individuals most at risk.
Absolute neutrophil count and adverse drug reaction monitoring during clozapine treatment: consensus guidelines from a global Delphi panel.
Despite its superior effectiveness for treatment-resistant schizophrenia, clozapine has a high burden of adverse drug reactions (ADRs), which require monitoring and treatment. This global Delphi study has established consensus guidelines for absolute neutrophil count (ANC) thresholds for consideration of clozapine cessation and provided monitoring protocols for ADR management. Recommendations include lowering ANC cessation thresholds to 1·0 × 109 cells per L (0·5 × 109 cells per L for Duffy antigen receptor for chemokines-null individuals) and discontinuing routine ANC monitoring after 2 years. Comprehensive ADR monitoring every 3 months should address the metabolic syndrome, constipation, gastro-oesophageal reflux, sialorrhea, nocturnal enuresis, tachycardia, sleep apnoea, sedation, and other ADRs. Consumer representatives underscored the need for shared decision-making, streamlined monitoring, and accessible patient education. Although barriers persist, these findings support updating global policies to reduce burden on patients, enhance adherence, and optimise clinical outcomes. Incorporating evidence-based guidelines into practice could transform clozapine care, balancing safety with practicality to improve the lives of those with treatment-resistant schizophrenia.
Automated quality control of T1-weighted brain MRI scans for clinical research: methods comparison and design of a quality prediction classifier
T1-weighted (T1w) MRI is widely used in clinical neuroimaging for studying brain structure and its changes, including those related to neurodegenerative diseases, and as anatomical reference for analysing other modalities. Ensuring high-quality T1w scans is vital as image quality affects reliability of outcome measures. However, visual inspection can be subjective and time-consuming, especially with large datasets. The effectiveness of automated quality control (QC) tools for clinical cohorts remains uncertain. In this study, we used T1w scans from elderly participants within ageing and clinical populations to test the accuracy of existing QC tools with respect to visual QC and to establish a new quality prediction framework for clinical research use. Four datasets acquired from multiple scanners and sites were used (N = 2438, 11 sites, 39 scanner manufacturer models, 3 field strengths – 1.5T, 3T, 2.9T, patients and controls, average age 71 ± 8 years). All structural T1w scans were processed with two standard automated QC pipelines (MRIQC and CAT12). The agreement of the accept-reject ratings was compared between the automated pipelines and with visual QC. We then designed a quality prediction framework that combines the QC measures from the existing automated tools and is trained on clinical research datasets. We tested the classifier performance using cross-validation on data from all sites together, also examining the performance across diagnostic groups. We then tested the generalisability of our approach when leaving one site out and explored how well our approach generalises to data from a different scanner manufacturer and/or field strength from those used for training, as well as on an unseen new dataset of healthy young participants with movement related artefacts. Our results show significant agreement between automated QC tools and visual QC (Kappa=0.30 with MRIQC predictions; Kappa=0.28 with CAT12’s rating) when considering the entire dataset, but the agreement was highly variable across datasets. Our proposed robust undersampling boost (RUS) classifier achieved 87.7% balanced accuracy on the test data combined from different sites (with 86.6% and 88.3% balanced accuracy on scans from patients and controls respectively). This classifier was also found to be generalisable on different combinations of training and test datasets (average balanced accuracy of leave-one-site-out = 78.2%; exploratory models on field strengths and manufacturers = 77.7%; movement related artefact dataset when including 1% scans in the training = 88.5%). While existing QC tools may not be robustly applicable to datasets comprised of older adults, they produce quality metrics that can be leveraged to train a more robust quality control classifiers for ageing and clinical cohorts.
Call up the (cognitive) reserves: how adult socialisation and education influences cognition in the UK Biobank.
INTRODUCTION: Dementia involves the loss of memory and degradation of cognitive function. Crucially, the onset of dementia may be prevented by identifying and modifying relevant risk factors years before disease onset in midlife. Commonly described modifiable risk factors include social isolation and educational attainment. Here, we aim to understand the relationships between adult activities and their effects on cognition related to mid-life aging in terms of where and how people live. METHODS: We analysed data from the UK Biobank (N = 502,165, Mage = 56.53, SDage = 8.09, 54.40% female). In particular, our path analysis investigated the associations between years of education in childhood, education later in life, social activities in adulthood, built environment (i.e., coastal distance and percentage of greenspace), socioeconomic status (i.e., Townsend deprivation index), and cognitive functions (i.e., memory, executive function, and abstract reasoning). RESULTS: Adult education and social activities predict better cognition. Being deprived predicts attendance in adult education classes, but fewer social activities and poorer cognition. Moreover, living in areas with less greenspace and being further away from coastlines predict attendance in adult education classes; however, only greenspace predicts participation in social activities. Finally, less greenspace and further coastal distance support abstract reasoning, whereas further coastal distance predicts poorer executive function. CONCLUSION: We demonstrate the potential utility of adult education and social activities which may offset the detrimental effects of deprivation. Accordingly, we argue for improved access to adult social programs in deprived/underserviced areas in the United Kingdom.
Engagement and attrition in digital mental health: current challenges and potential solutions.
In digital mental health engagement rates are consistently low, which may limit its effects. Using an international multidisciplinary consensus method, including lived experience expertise and a systematic review, we identified three key challenges: (i) lack of agreed metrics for engagement; (ii) lack of evidence on how better engagement improves outcomes; (iii) lack of standards for user involvement. Three potential solutions encompassed: (i) standardisation of frameworks for reporting engagement metrics and optimal doses of digital tools, (ii) measuring engagement with more precise reporting of outcomes, including potential harms; (iii) defining standards of user involvement (including appropriate diversity, and clinician as well as user input). Digital interventions have real potential in meeting the shortfall in service provision for mental health, but this will require focus on high quality research studies of the underlying mechanisms of engagement and optimal outcomes. Our findings identify and highlight the next best steps in this process.
Economic evaluation of caregiver interventions for children with developmental disabilities: A scoping review.
Globally, families with children with developmental disabilities (DDs) experience challenges, including social isolation, stigma, and poverty, especially in low-income settings in Africa. Most children with DDs in Africa remain unidentified and receive no formal support. Caregiver interventions focusing on education and training for the carers/parents have been shown to be adaptable and low intensity in implementation, although the economic evidence is limited. This review aimed to describe the evidence and methodological aspects of economic evaluations for caregiver interventions for DDs. The Arksey and O'Malley framework was applied. Seven electronic databases, grey literature and cited references were systematically searched to identify eligible studies. published from 1993 to 2023. We assessed the quality of the included studies using the Drummond checklist. Data were systematically extracted, tabulated, and qualitatively synthesised using inductive thematic analysis. From 7811 articles, twenty studies all in high-income countries were included, and focused on caregiver interventions for autism spectrum disorder (n = 7), attention deficit hyperactivity disorder (ADHD) (n = 6), disruptive behaviour and behaviour problems with ADHD (n = 5), intellectual disabilities (n = 1) and language delay (n = 1). Economic evaluation analyses included cost effectiveness (n = 11), costing (n = 3), cost utility (n = 2), cost consequence (n = 1) cost benefit (n = 1), and combined analyses (n = 2). Nine studies reported the interventions as cost effective and five studies reported the intervention to be cost saving. The main methodological challenges were related to costing, outcome measurement in children and the appropriate time horizon for modelling. Caregiver interventions demonstrate cost-effectiveness, with the available evidence supporting the adoption of the interventions as a promising avenue to strengthen access and reduce the associated healthcare costs. The identified key methodological challenges highlighted further research areas. Prioritizing more economic evaluation studies in this area would inform decision-making on efficient resource allocation, promote inclusivity and equitable access to services for children with DDs.
In Children, N-Methyl-D-Aspartate Receptor Antibody Encephalitis Incidence Exceeds That of Japanese Encephalitis in Vietnam.
BACKGROUND: The recognition of autoimmune causes of encephalitis has led to epidemiological shifts in the worldwide characteristics of encephalitis. N-methyl-D-aspartate receptor (NMDAR) antibody encephalitis leads to well-established complex neuropsychiatric manifestations. In low- and middle-income countries, including Vietnam, its relative incidence, especially in children, is unknown and most neurologists currently consider infectious encephalitis prior to autoimmune etiologies. METHODS: The study was prospectively conducted at Children's Hospital 1 in Ho Chi Minh City between March 2020 and December 2022. Any child admitted to the Department of Infectious Diseases and Neurology fulfilling the case definition of encephalitis was eligible to participate. Cerebrospinal fluid samples were collected alongside meta-clinical data for analysis. RESULTS: We recruited 164 children with a clinical diagnosis of encephalitis. Etiologies were determined as NMDAR antibody encephalitis in 23 of 164 cases (14.0%), Japanese encephalitis virus in 14 of 164 (8.5%), and herpes simplex virus in 4 of 164 (2.4%). Clinical categorizations suggested idiopathic viral encephalitis in another 71 (43.3%), and autoimmune encephalitis of unknown origin in the remaining 52. Factors including demographics, specific clinical features, cerebrospinal fluid and electroencephalogram findings, and length of hospital stay were significantly different between NMDAR antibody encephalitis and Japanese encephalitis. CONCLUSIONS: At a tertiary children's hospital in Vietnam, the prevalence of NMDAR antibody encephalitis exceeds that of Japanese encephalitis, the most common infectious encephalitis cause in Southeast Asia. NMDAR antibody encephalitis is associated with long hospital stay and poor outcomes. These findings should change pediatric diagnostics, to earlier consider autoimmune treatments in this clinical setting.
Genomic risk prediction for type 2 diabetes in Australian individuals aged 70 years and older.
AIMS: The utility of a polygenic score (PGS) for type 2 diabetes (T2D) has been demonstrated in the general adult population. However, while previous studies have included older adults within broader age ranges, the performance of PGS specifically in older individuals aged ≥70 years remains unclear. We aimed to evaluate the predictive utility of a PGS in an older cohort. MATERIALS AND METHODS: We derived a PGS in 12 174 Australian participants aged ≥70 years from the ASPREE trial, with a median follow-up of 4.6 years. T2D was defined by self-report, commencement of glucose-lowering medication, or a fasting plasma glucose of ≥7.0 mmol/L. Multivariable logistic and Cox models examined associations between the PGS and baseline and incident T2D, adjusting for clinical risk factors. Risk prediction was evaluated using area under the curve (AUC), C-index, and net reclassification improvement (NRI). RESULTS: At baseline, 1150 (9.4%) participants had prevalent T2D. During follow-up, an additional 590 (4.8%) developed incident T2D. Per standard deviation, the PGS was significantly associated with baseline (odds ratio: 2.39 [95% CI: 2.19-2.61]) and incident (hazard ratio: 1.55 [1.40-1.71]) T2D. The PGS improved prediction over the clinical risk factors, increasing the AUC from 0.70 to 0.79, and C-index from 0.67 to 0.71 (both p
Tacrolimus monitoring in renal transplantation: A comparison between high-performance liquid chromatography and immunoassay
It is recommended that specific methods of tacrolimus monitoring rather than immunoassays, which overestimate tacrolimus levels, should be used in transplant recipients. Direct comparison of these techniques, however, has not been conducted in renal transplantation. In this study, 40 renal transplant recipients with tacrolimus monitoring by microparticle enzyme immunoassay (MEIA; target trough level 10 to 15 ng/mL) were compared with 40 patients monitored by high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS; target trough level 8 to 13 ng/mL). All patients received anti CD25 antibody induction and mycophenolate mofetil in a steroid-sparing protocol. No differences were seen between MEIA and HPLC-MS groups in patient demographics. All patients were followed for 6 months. Patient survival was 100% in both groups; graft survival was 100% in the MEIA group and 97.5% in the HPLC-MS group. The groups did not differ in the number of dose changes required in the first 6 months or in the number of patients displaying tacrolimus levels within target range at 3 and 6 months. Delayed graft function occurred in 14 patients in the MEIA group and 12 patients in the HPLC-MS group (P = NS). Biopsy-proven acute rejection occurred in four patients in the MEIA group and one patient in the HPLC-MS group (P
Exploring early childhood development programming in Kenya’s arid and semi-arid lands
Background: Promoting high-quality early childhood development (ECD) is vital for individuals’ physical and social well-being and yields significant societal returns. However, children in marginalised regions like Kenya’s arid and semi-arid lands (ASALs) face significant barriers to accessing quality ECD services. Aim: This study aimed to document existing ECD services in Kenya’s ASAL areas, including their availability, types and key characteristics; identify gaps in their provision and propose solutions to enhance access and quality. Setting: This qualitative study was conducted in 10 ASAL counties in Kenya. Methods: Using purposive and snowball sampling techniques, 103 key informants, including pre-primary teachers, parents, healthcare workers, religious leaders and county ECD coordinators, were interviewed. The interviews were audio-recorded, transcribed verbatim and analysed thematically. Results: The study found that while diverse ECD programmes exist in ASAL regions, their quality and effectiveness are hindered by challenges such as inadequate funding, insecurity, extreme weather events, food insecurity, poor infrastructure, inadequate healthcare access and limited early learning opportunities. Recommendations include increasing ECD funding, improving healthcare, enhancing early learning opportunities, promoting livelihood diversification and addressing security and food insecurity. Conclusion: Despite investments in ECD programmes, significant challenges persist, underscoring the need to provide children with high-quality services that foster nurturing care and mitigate risks to their development. This study highlights the urgency of adopting a multi-sectoral approach to strengthen ECD programmes and services in Kenya’s ASAL. Contribution: This article contributes to the scarce literature on ECD programming in Kenya’s ASALs by documenting existing ECD services, identifying critical gaps in their provision and offering actionable recommendations to address barriers to programme quality and effectiveness.
The cognitive neuroscience of ketamine in major depression.
Ketamine's potential as a rapid-acting antidepressant was first identified in 2000, despite its long-standing use as an anesthetic agent. Clinically, ketamine alleviates depressive symptoms, including the difficult to treat symptom of anhedonia, within hours, with the effects of a single dose lasting for days. Since then, research has focused on uncovering the mechanisms underlying its rapid antidepressant effects in both humans and animal models. While its molecular and cellular effects have been extensively characterized, its impact on cognitive and neuropsychological mechanisms - potential mediators of its clinical efficacy - remains an area of ongoing investigation. Preclinical studies suggest that ketamine rapidly influences the lateral habenula (involved in punishment processing) and fronto-striatal (reward) systems, reverses negative affective biases in established memories, and promotes long-term stress resilience. Translating these findings to human models is crucial, and emerging evidence suggests that ketamine engages similar mechanisms in healthy volunteer and patient groups. However, its clinical application is constrained by acute side effects and an unknown long-term safety profile. Further research into ketamine's mechanisms of action will be essential to inform the development of novel, safer, and more accessible rapid-acting antidepressants.