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Sodium fluoride preserves blood metabolite integrity for biomarker discovery in large-scale, multi-site metabolomics investigations.
Background: Metabolite profiling of blood by nuclear magnetic resonance (NMR) is invaluable to clinical biomarker discovery. To ensure robustness, biomarkers require validation in large cohorts and across multiple centres. However, collection procedures are known to impact on the stability of biofluids that may, in turn, degrade biomarker signals. We trialled three blood collection tubes with the aim of solving technical challenges due to preanalytical variation in blood metabolite levels that are common in cohort studies. Methods: We first investigated global NMR-based metabolite variability between biobanks, including the large-scale UK Biobank and TwinsUK biobank of the general UK population, and more targeted biobanks derived from multicentre clinical trials relating to inflammatory bowel disease. We then compared the blood metabolome of 12 healthy adult volunteers when collected into either sodium fluoride/potassium oxalate, lithium heparin, or serum blood tubes using different pre-processing parameters. Results: Preanalytical variation in the method of blood collection strongly influences metabolite composition within and between biobanks. This variability can largely be attributed to glucose and lactate. In the healthy control cohort, the fluoride oxalate collection tube prevented fluctuation in glucose and lactate levels for 24 hours at either 4 °C or room temperature (20 °C). Conclusions: Blood collection into a fluoride oxalate collection tube appears to preserve the blood metabolome with delayed processing up to 24 hours at 4 °C. This method may be considered as an alternative when rapid processing is not feasible.
The prevalence of premenstrual dysphoric disorder: Systematic review and meta-analysis.
BACKGROUND: Premenstrual dysphoric disorder is characterised by symptoms confined to the premenstrual phase of the menstrual cycle. Confirmed diagnosis requires prospective monitoring of symptoms over two cycles, otherwise the diagnosis is provisional. We aimed to measure the point prevalence of premenstrual dysphoric disorder. METHODS: We searched for studies of prevalence using MEDLINE, EMBASE, PsycINFO and PubMed. For each study, the total sample size and number of cases were extracted. The prevalence across studies was calculated using random effects meta-analysis with a generalised linear mixed model. Potential sources of heterogeneity were explored by meta-regression and subgroup analyses. Pre-registration was with PROSPERO (CRD42021249249). RESULTS: 44 studies with 48 independent samples met inclusion criteria, consisting of 50,659 participants. The pooled prevalence was 3.2 % (95 % confidence intervals: 1.7 %-5.9 %) for confirmed and 7.7 % (95 % confidence intervals: 5.3 %-11.0 %) for provisional diagnosis. There was high heterogeneity across all studies (I2 = 99 %). Sources of heterogeneity identified by meta-regression were continent of sample (p
Effectiveness of Violence Prevention Interventions: Umbrella Review of Research in the General Population.
To address the societal harms of violence, many violence prevention interventions have been developed, tested, and implemented in the general population. These have been reported in systematic reviews and meta-analyses, which have typically focused on one type of intervention or outcome. We aimed to provide a comprehensive overview of the current evidence regarding the effectiveness of different psychosocial interventions in reducing all forms of violence toward others. We have conducted an umbrella review of previous meta-analyses using standard approaches and converted findings on effectiveness into odds ratios. We tested for the underlying quality of the meta-analytic evidence by examining heterogeneity, excess statistical significance, prediction intervals, and small study effects. We identified 16 meta-analyses, including nine investigating psychosocial interventions, and five legislative and policy changes. Most meta-analyses reported positive effects of tested interventions. The strongest effects were found for sports-based initiatives, and the weakest for general population programs aimed at early childhood, youth development, and reducing sexual assault perpetration by men. Legislative changes had varying effectiveness. We conclude that simple, scalable, and cost-efficient programs, such as sport-based initiatives, have the clearest empirical support as population-based approaches to violence prevention.
Incidence of chikungunya virus infections among Kenyan children with neurological disease: a prospective cohort study
<h4>ABSTRACT</h4> <h4>Background</h4> Neurological complications due to chikungunya virus (CHIKV) infection have been described in different parts of the world, with children being disproportionately affected. However, the burden of CHIKV-associated neurological disease in Africa is currently unknown. <h4>Methods</h4> We estimated the incidence of CHIKV infection among children hospitalised with neurological disease in coastal Kenya. We used reverse-transcriptase polymerase chain reaction (RT-PCR) to systematically test for CHIKV in cerebrospinal fluid (CSF) samples from children aged <16 years hospitalised with symptoms of neurological disease at Kilifi County Hospital between January 2014 and December 2018. Clinical records were linked to the Kilifi Health and Demographic Surveillance System and population incidence rates of CHIKV infection estimated. <h4>Findings</h4> There were 18,341 paediatric admissions during the 5-year study period, of which 4,332 (24%) had CSF collected. The most common clinical reasons for CSF collection were impaired consciousness, seizures and coma (47%, 22% and 21% of all collections, respectively). After acute investigations done for immediate clinical care, CSF samples were available for 3,980 admissions, of which 367 (9.2%) were CHIKV RT-PCR positive. The annual incidence of CHIKV-associated neurological disease varied between 13 to 58 episodes per 100,000 person-years among all children <16 years old. Among children aged <5 years, the incidence of CHIKV-associated neurological disease was 77 per 100,000 person-years, compared with 20 per 100,000 for cerebral malaria and 7 per 100,000 for bacterial meningitis during the study period. <h4>Interpretation</h4> Although not previously recognized, CHIKV-associated neurological disease is common in coastal Kenya and a significant public health burden.
Patterns of neurobehavioral functioning in school-aged survivors of neonatal jaundice and hypoxic-ischemic encephalopathy in Kilifi, Kenya: A cross-sectional study
<ns4:p><ns4:bold>Background:</ns4:bold> Studies in high-income countries have reported that school-aged children who survive neonatal jaundice (NNJ) and hypoxic-ischemic encephalopathy (HIE) develop long-term neurocognitive problems. However, less is known about the patterns of functioning in school-aged survivors of NNJ and HIE in sub-Saharan Africa. This study examined patterns of functioning in school-aged children who survived NNJ and HIE in Kilifi, Kenya.</ns4:p><ns4:p> <ns4:bold>Methods:</ns4:bold> This is a cross-sectional study that included 107 survivors of NNJ/HIE (64 with NNJ, 43 with HIE), aged 6-12 years, admitted to Kilifi County Hospital on the Kenyan Coast. The Gross Motor Function Classification System (GMFCS), Adapted Communication Profile, Raven’s Coloured Progressive Matrices (RCPM) and an epilepsy screening tool were used to assess gross motor function, communication function, intellectual functioning, and epilepsy, respectively.</ns4:p><ns4:p> <ns4:bold>Results:</ns4:bold> Most of the survivors of NNJ (95.2%) and HIE (95.3%) had no impairments in gross motor functioning. A small percentage of the children in the NNJ and HIE groups had profound problems in their communication (4.7% and 4.7%); expressive communication function (4.7% and 4.7%); social functions (3.1% and 2.3%); receptive communication (4.7% and 2.3%); and communicative effectiveness (4.7% and 2.3%). Cognitive impairment was reported in 10.9% and 11.9% for NNJ and HIE survivors, respectively. Active epilepsy was detected in 1.6% of survivors of NNJ and 2.3% of survivors of HIE. A subgroup of severe NNJ and HIE survivors without co-occurring conditions had the worst intellectual and active epilepsy outcomes. All children had normal hearing and visual functioning except one participant who presented with mild visual acuity problems.</ns4:p><ns4:p> <ns4:bold>Conclusions:</ns4:bold> Most school-aged children who survive with NNJ and HIE have normal motor and communication function; however, one in ten are likely to present with lowered intellectual functioning compared to the normative sample.</ns4:p>
Young people's data governance preferences for their mental health data: MindKind Study findings from India, South Africa, and the United Kingdom.
Mobile devices offer a scalable opportunity to collect longitudinal data that facilitate advances in mental health treatment to address the burden of mental health conditions in young people. Sharing these data with the research community is critical to gaining maximal value from rich data of this nature. However, the highly personal nature of the data necessitates understanding the conditions under which young people are willing to share them. To answer this question, we developed the MindKind Study, a multinational, mixed methods study that solicits young people's preferences for how their data are governed and quantifies potential participants' willingness to join under different conditions. We employed a community-based participatory approach, involving young people as stakeholders and co-researchers. At sites in India, South Africa, and the UK, we enrolled 3575 participants ages 16-24 in the mobile app-mediated quantitative study and 143 participants in the public deliberation-based qualitative study. We found that while youth participants have strong preferences for data governance, these preferences did not translate into (un)willingness to join the smartphone-based study. Participants grappled with the risks and benefits of participation as well as their desire that the "right people" access their data. Throughout the study, we recognized young people's commitment to finding solutions and co-producing research architectures to allow for more open sharing of mental health data to accelerate and derive maximal benefit from research.
MindKind: A mixed-methods protocol for the feasibility of global digital mental health studies in young people.
Background: While an estimated 14-20% of young adults experience mental health conditions worldwide, the best strategies for prevention and management are not fully understood. The ubiquity of smartphone use among young people makes them excellent candidates for collecting data about lived experiences and their relationships to mental health. However, not much is known about the factors affecting young peoples' willingness to share information about their mental health. Objective: We aim to understand the data governance and engagement strategies influencing young peoples' (aged 16-24) participation in app-based studies of mental health. We hypothesize that willingness to participate in research is influenced by involvement in how their data is collected, shared, and used. Methods: Here, we describe the MindKind Study, which employs mixed methods to understand the feasibility of global, smartphone-based studies of youth mental health. A pilot 12-week app-based substudy will query participants' willingness to engage with remote mental health studies. Participants will be randomized into one of four different data governance models designed to understand their preferences, as well as the acceptability of models that allow them more or less control over how their data are accessed and used. Enrolees will receive one of two different engagement strategies. A companion qualitative study will employ a deliberative democracy approach to examine the preferences, concerns and expectations of young people, with respect to remote mental health research. We also detail our engagement with young people as co-researchers in this study. This pilot study is being conducted in India, South Africa and the United Kingdom. Conclusions: This study is expected to generate new insights into the feasibility of, and best practices for, remote smartphone-based studies of mental health in youth and represents an important step toward understanding which approaches could help people better manage their mental health.
Promoting positive development among refugee adolescents.
Of the estimated 35.3 million refugees around the world (UNHCR, Figures at a Glance, 2022), approximately 50% are children under the age of 18. Refugee adolescents represent a unique group as they navigate developmental tasks in an unstable and often threatening environment or in resettlement contexts in which they often face marginalization. In addition to physiological, social, and psychological changes that mark adolescence, refugee youth often face traumatic experiences, acculturative stress, discrimination, and a lack of basic resources. In this consensus statement, we examine research on refugee adolescents' developmental tasks, acculturative tasks, and psychological adjustment using Suárez-Orozco and colleague's integrative risk and resilience model for immigrant-origin children and youth proposed by Suárez-Orozco et al. Finally, we discuss recommendations-moving from proximal to more distal contexts.
Maternal prenatal distress exposure negatively associates with the stability of neonatal frontoparietal network.
Maternal prenatal distress (PD), frequently defined as in utero prenatal stress exposure (PSE) to the developing fetus, influences the developing brain and numerous associations between PSE and brain structure have been described both in neonates and in older children. Previous studies addressing PSE-linked alterations in neonates' brain activity have focused on connectivity analyses from predefined seed regions, but the effects of PSE at the level of distributed functional networks remains unclear. In this study, we investigated the impact of prenatal distress on the spatial and temporal properties of functional networks detected in functional MRI data from 20 naturally sleeping, term-born (age 25.85 ± 7.72 days, 11 males), healthy neonates. First, we performed group level independent component analysis (GICA) to evaluate an association between PD and the identified functional networks. Second, we searched for an association with PD at the level of the stability of functional networks over time using leading eigenvector dynamics analysis (LEiDA). No statistically significant associations were detected at the spatial level for the GICA-derived networks. However, at the dynamic level, LEiDA revealed that maternal PD negatively associated with the stability of a frontoparietal network. These results imply that maternal PD may influence the stability of frontoparietal connections in neonatal brain network dynamics and adds to the cumulating evidence that frontal areas are especially sensitive to PSE. We advocate for early preventive intervention strategies regarding pregnant mothers. Nevertheless, future research venues are required to assess optimal intervention timing and methods for maximum benefit.
Violations of the fluctuation-dissipation theorem reveal distinct nonequilibrium dynamics of brain states
The brain is a nonequilibrium system whose dynamics change in different brain states, such as wakefulness and deep sleep. Thermodynamics provides the tools for revealing these nonequilibrium dynamics. We used violations of the fluctuation-dissipation theorem to describe the hierarchy of nonequilibrium dynamics associated with different brain states. Together with a whole-brain model fitted to empirical human neuroimaging data, and deriving the appropriate analytical expressions, we were able to capture the deviation from equilibrium in different brain states that arises from asymmetric interactions and hierarchical organization.
Magnetic resonance imaging findings in Kenyans and South Africans with active convulsive epilepsy: An observational study.
OBJECTIVE: Focal epilepsy is common in low- and middle-income countries. The frequency and nature of possible underlying structural brain abnormalities have, however, not been fully assessed. METHODS: We evaluated the possible structural causes of epilepsy in 331 people with epilepsy (240 from Kenya and 91 from South Africa) identified from community surveys of active convulsive epilepsy. Magnetic resonance imaging (MRI) scans were acquired on 1.5-Tesla scanners to determine the frequency and nature of any underlying lesions. We estimated the prevalence of these abnormalities using Bayesian priors (from an earlier pilot study) and observed data (from this study). We used a mixed-effect modified Poisson regression approach with the site as a random effect to determine the clinical features associated with neuropathology. RESULTS: MRI abnormalities were found in 140 of 240 (modeled prevalence = 59%, 95% confidence interval [CI]: 53%-64%) of people with epilepsy in Kenya, and in 62 of 91 (modeled prevalence = 65%, 95% CI: 57%-73%) in South Africa, with a pooled modeled prevalence of 61% (95% CI: 56%-66%). Abnormalities were common in those with a history of adverse perinatal events (15/23 [65%, 95% CI: 43%-84%]), exposure to parasitic infections (83/120 [69%, 95% CI: 60%-77%]) and focal electroencephalographic features (97/142 [68%, 95% CI: 60%-76%]), but less frequent in individuals with generalized electroencephalographic features (44/99 [44%, 95% CI: 34%-55%]). Most abnormalities were potentially epileptogenic (167/202, 82%), of which mesial temporal sclerosis (43%) and gliosis (34%) were the most frequent. Abnormalities were associated with co-occurrence of generalized non-convulsive seizures (relative risk [RR] = 1.12, 95% CI: 1.04-1.25), lack of family history of seizures (RR = 0.91, 0.86-0.96), convulsive status epilepticus (RR = 1.14, 1.08-1.21), frequent seizures (RR = 1.12, 1.04-1.20), and reported use of anti-seizure medication (RR = 1.22, 1.18-1.26). SIGNIFICANCE: MRI identified pathologies are common in people with epilepsy in Kenya and South Africa. Mesial temporal sclerosis, the most common abnormality, may be amenable to surgical correction. MRI may have a diagnostic value in rural Africa, but future longitudinal studies should examine the prognostic role.
Healthcare utilization by children with neurological impairments and disabilities in rural Kenya: a retrospective cohort study combined with secondary analysis of audit data
<h4>Background: </h4> There is a paucity of data on healthcare utilization by children with neurological impairments (NI) in sub-Saharan Africa. We determined the rate, risk factors, causes, and outcomes of hospital admission and utilization patterns for rehabilitative care among children with NI in a defined rural area in Kenya. <h4>Methods: </h4> We designed two sub-studies to address the primary objectives. Firstly, we retrospectively observed 251 children aged 6–9 years with NI and 2162 age-matched controls to determine the rate, causes and outcomes of hospitalization in a local referral hospital. The two cohorts were identified from an epidemiological survey conducted in 2015 in a defined geographical area. Secondly, we reviewed hospital records to characterize utilization patterns for rehabilitative care. <h4>Results: </h4> Thirty-four in-patient admissions occurred in 8503 person-years of observation (PYO), yielding a crude rate of 400 admissions per 100 000 PYO (95% confidence interval (Cl): 286–560). The risk of admission was similar between cases and controls (rate ratio=0.70, 95%CI: 0.10–2.30, p = 0.31). The presence of electricity in the household was associated with reduced odds of admission (odds ratio=0.32, 95% Cl: 0.10–0.90, p < 0.01). Seizures and malaria were the main causes of admission. We confirmed six (0.3%) deaths during the follow-up period. Over 93% of outpatient paediatric visits for rehabilitative care were related to cerebral palsy and intellectual developmental delay. Health education (87%), rehabilitative exercises (79%) and assistive technology (64%) were the most common interventions. <h4>Conclusions: </h4> Surprisingly, the risk of hospitalization was not different between children with NI and those without, possibly because those with severe NI who died before this follow-up were under seclusion and restraint in the community. Evidence-based and tailored rehabilitative interventions are urgently required based on the existing secondary data.