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There’s growing concern about the far-reaching impact COVID-19 may have on people’s mental health across the globe, with the consequences likely to be present for longer and peak later than the actual pandemic.
Vancomycin-Resistant E. faecium: Addressing Global and Clinical Challenges
Antimicrobial resistance (AMR) poses a profound threat to modern healthcare, with vancomycin-resistant Enterococcus faecium (VREfm) emerging as a particularly resilient and clinically significant pathogen. This mini-review examines the biological mechanisms underpinning VREfm resistance, including biofilm formation, stress tolerance, and the acquisition of resistance genes such as vanA and vanB. It also explores the behavioural, social, and healthcare system factors that facilitate VREfm transmission, highlighting disparities in burden across vulnerable populations and low-resource settings. Prevention strategies are mapped across the disease pathway, spanning primary, secondary, and tertiary levels, with a particular focus on the role and evolving challenges of antimicrobial stewardship programmes (ASP). We highlight emerging threats, such as rifaximin-induced cross-resistance to daptomycin, which challenge conventional stewardship paradigms. Finally, we propose future directions to enhance global surveillance, promote equitable stewardship interventions, and accelerate the development of innovative therapies. Addressing VREfm requires a coordinated, multidisciplinary effort to safeguard the efficacy of existing antimicrobials and protect at-risk patient populations.
Hypothalamic volume, sleep, and APOE genotype in cognitively healthy adults
INTRODUCTION: Sleep dysfunction in those at higher risk of dementia may be associated with early structural changes to the hypothalamus. METHODS: We used multivariate regression to analyze self-reported sleep (Pittsburgh Sleep Quality Index [PSQI]) from cognitively healthy participants in the PREVENT Dementia and Alzheimer's and Families (ALFA) studies (n = 1939), stratified by apolipoprotein E (APOE) genotype as homozygotes, heterozygotes, and non-carriers. FreeSurfer was used to extract hypothalamic subunit volumes from T1-weighted magnetic resonance images. RESULTS: APOE ε4 homozygotes had a larger anterior–superior hypothalamus compared to heterozygotes and non-carriers, an effect which was driven by younger people in the cohort. APOE ε4 carriers had a higher PSQI global score after age 55, and smaller anterior–superior and tubular–superior subunits were associated with more sleep disturbances. Sleep duration and efficiency worsened with age, but only in participants with a small anterior–inferior hypothalamus. DISCUSSION: This suggests that aging and APOE ε4 are associated with hypothalamic changes, highlighting mechanisms linking sleep dysfunction to dementia. Highlights: Apolipoprotein E (APOE) ε4 homozygotes ha a larger anterior–superior hypothalamus. APOE ε4 carriers have worse sleep, but only after age 55. Worse sleep in APOE ε4 carriers was associated with smaller hypothalamic subunits. Higher age was associated with worse sleep in people with a small hypothalamus.
Sociodemographic influences on substance use in psychosis in an African cohort.
BACKGROUND: Substance use is common among individuals with psychotic disorders, but limited research exists on the variations in substance use across countries in Africa. This study aims to investigate the frequency of alcohol, tobacco, cannabis, and khat consumption in individuals with bipolar disorder (BD) and schizophrenia (SCZ) across four African countries: South Africa, Ethiopia, Kenya, and Uganda. METHODS: We utilized data from the Neuropsychiatric Genetics of African Populations-Psychosis project, a large case-control study which will soon have genetic data on over 42,000 participants, half with psychosis. Information on substance use was collected using the Alcohol, Smoking and Substance Involvement Screening Test v3 (ASSIST). The outcome was categorized into never (lifetime usage, no), irregular usage (weekly or monthly) and regular (daily use) based on reported frequency in the past three months. Each substance was modeled individually as an outcome in ordinal regression model adjusting for demographic factors of sex, education and country. Stratified analyses were performed to assess country-specific effects. RESULTS: Individuals with BD had significantly higher odds of alcohol consumption compared to those with SCZ. Males showed higher odds of alcohol, tobacco, and khat consumption compared to females. Significant variations in alcohol, tobacco, and cannabis consumption were observed across different study countries. Education level was significantly associated with khat consumption, with higher education levels associated with lower odds of consumption. CONCLUSION: Country and sex-specific differences in substance use behaviors exist in a large-scale African case-control study of people with psychosis. The findings here are in line with previous work regarding sex and regional differences, though they differ from studies conducted in US populations in that minimal evidence was found to support a relationship between level of education and frequency of substance use for any of the substances studied. This suggests that there may be distinct sociodemographic correlates of substance use in Africa and highlights the critical need to consider individuals of diverse ancestry in large-scale studies while also taking into account regional differences when examining substance use behaviors.
Global, Regional, and National Burden of Nontraumatic Subarachnoid Hemorrhage: The Global Burden of Disease Study 2021.
IMPORTANCE: Nontraumatic subarachnoid hemorrhage (SAH) represents the third most common stroke type with unique etiologies, risk factors, diagnostics, and treatments. Nevertheless, epidemiological studies often cluster SAH with other stroke types leaving its distinct burden estimates obscure. OBJECTIVE: To estimate the worldwide burden of SAH. DESIGN, SETTING, AND PARTICIPANTS: Based on the repeated cross-sectional Global Burden of Disease (GBD) 2021 study, the global burden of SAH in 1990 to 2021 was estimated. Moreover, the SAH burden was compared with other diseases, and its associations with 14 individual risk factors were investigated with available data in the GBD 2021 study. The GBD study included the burden estimates of nontraumatic SAH among all ages in 204 countries and territories between 1990 and 2021. EXPOSURES: SAH and 14 modifiable risk factors. MAIN OUTCOMES AND MEASURES: Absolute numbers and age-standardized rates with 95% uncertainty intervals (UIs) of SAH incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) as well as risk factor-specific population attributable fractions (PAFs). RESULTS: In 2021, the global age-standardized SAH incidence was 8.3 (95% UI, 7.3-9.5), prevalence was 92.2 (95% UI, 84.1-100.6), mortality was 4.2 (95% UI, 3.7-4.8), and DALY rate was 125.2 (95% UI, 110.5-142.6) per 100 000 people. The highest burden estimates were found in Latin America, the Caribbean, Oceania, and high-income Asia Pacific. Although the absolute number of SAH cases increased, especially in regions with a low sociodemographic index, all age-standardized burden rates decreased between 1990 and 2021: the incidence by 28.8% (95% UI, 25.7%-31.6%), prevalence by 16.1% (95% UI, 14.8%-17.7%), mortality by 56.1% (95% UI, 40.7%-64.3%), and DALY rate by 54.6% (95% UI, 42.8%-61.9%). Of 300 diseases, SAH ranked as the 36th most common cause of death and 59th most common cause of DALY in the world. Of all worldwide SAH-related DALYs, 71.6% (95% UI, 63.8%-78.6%) were associated with the 14 modeled risk factors of which high systolic blood pressure (population attributable fraction [PAF] = 51.6%; 95% UI, 38.0%-62.6%) and smoking (PAF = 14.4%; 95% UI, 12.4%-16.5%) had the highest attribution. CONCLUSIONS AND RELEVANCE: Although the global age-standardized burden rates of SAH more than halved over the last 3 decades, SAH remained one of the most common cardiovascular and neurological causes of death and disabilities in the world, with increasing absolute case numbers. These findings suggest evidence for the potential health benefits of proactive public health planning and resource allocation toward the prevention of SAH.
African leadership in brain diplomacy: The Yaoundé declaration advances the global brain economy playbook for better brain Health.
Africa, the world's second-largest continent is home to 1.5 billion people, accounting for nearly 20% of the global population, (60% under age 25). By 2050, Africa's population will be 2.5 billion, and by 2035, more young Africans will be entering the workforce each year than in the rest of the world combined. Africa also hosts a rich social, cultural, and geopolitical diversity across its 5 geopolitical zones covering 54 countries. It is the most genetically, culturally, and linguistically diverse region on the planet. However, Africa's contribution to the global economy could be more significant if it urgently embraces the brain economy and leads in the development of new methodologies and approaches which can be exported around the world. In this paper, we explain our strategy to advance the Yaoundé Declaration for the Brain Economy, Brain Health, and Brain Capital. The Declaration has been endorsed by Cameroon's President, His Excellency Paul Biya, and demonstrates African leadership in global brain and society innovations, laying out a roadmap for how Africa can outcompete other economies by deftly deploying brain science-inspired policies and investments. We outline a new economic approach for African jobs, economic growth, sustainability, resilience, health, and well-being. The brain economy offers a broader framework than the current sustainable development goals (SDG) agenda. The Yaoundé Declaration is trans-disciplinary and cross-cutting across sectors: 32 sitting members of government from different sectors having co-authored this paper. It aligns with many aspects of the United Nations Pact for the Future and can accelerate the SDG.
A meta-analysis of the relationship between sleep and β-Amyloid biomarkers in Alzheimer's disease
Sleep has an important role for long-term memory consolidation. As deficits in learning and memory are clinical characteristics of Alzheimer's disease (AD), it has been suggested that disruptions in sleep-mediated consolidation processes are related to AD. Indeed, sleep disruptions and sleep disorders are often comorbid with AD and perhaps precede the onset of AD symptoms as a risk factor. Additionally, research has shown that sleep disruptions and disorders are associated with accumulation of β-amyloid (AB), a neuropathologic hallmark and biomarker of AD. However, the studies that have investigated the relationship between sleep disturbances and AB burden have been heterogenous in design and quality, leaving it unclear whether the overall effect is statistically significant. As such, this paper investigated the relationship between sleep disturbances and AB burden by meta-analytically integrating reported correlations that have been published to date. Results revealed that higher levels of cerebral AB (lower AB42/40 ratios) were related to shorter sleep durations, highlighting the importance of total sleep time in supporting the clearance of AB during slow-wave sleep. Herein we also controlled for heterogeneity in the included studies by conducting several moderator analyses, showing an important role for age, sex, cognitive impairment, sleep disorders, and education in influencing the associations between sleep disturbances and AB.
Glucagon-Like Peptide 1 Receptor Agonists and Mental Health: A Systematic Review and Meta-Analysis.
IMPORTANCE: People with obesity and diabetes have poorer psychiatric and cognitive outcomes and lower quality of life (QOL) compared with those without. Glucagon-like peptide 1 receptor agonists (GLP1-RAs) are treatments for diabetes and obesity that may also influence psychiatric outcomes. OBJECTIVE: To conduct a meta-analysis of randomized placebo-controlled trials to evaluate psychiatric, cognitive, and QOL outcomes with GLP1-RA treatment. DATA SOURCES: MEDLINE, Embase, PsycINFO, and CENTRAL databases were searched from inception through June 24, 2024. STUDY SELECTION: Double-blind placebo-controlled trials comparing GLP1-RA to placebo in adults with overweight/obesity and/or diabetes, reporting on psychiatric, cognition, or QOL outcomes, were included. DATA EXTRACTION AND SYNTHESIS: Data extraction was performed in parallel by 2 reviewers. Random-effects meta-analysis was performed. Effect size measures were log risk ratios (log[RR]) and standardized mean differences (Hedges g). The quality of studies was appraised using the Cochrane risk-of-bias tool (RoB2). Certainty of evidence was assessed via GRADEpro. MAIN OUTCOMES AND MEASURES: Main outcomes were risk of psychiatric adverse events (serious and nonserious) and change in mental health symptom severity, health-related quality of life, and cognition. RESULTS: Eighty randomized clinical trials involving 107 860 patients were included in the meta-analysis. The mean (SD) age of participants across studies in the meta-analysis was 60.1 (7.1) years; 43 251 were female (40.1%) and 64 608 male (59.9%). GLP1-RA treatment was not associated with a significant difference in risk of serious psychiatric adverse events (log[RR] = -0.02; 95% CI, -0.20 to 0.17; P = .87) and nonserious psychiatric adverse events (log[RR] = -0.03; 95% CI, -0.21 to 0.16], P = .76), or depressive symptom change (g = 0.02; 95% CI, -0.51 to 0.55; P = .94), compared with placebo. GLP1-RA treatment was associated with improvements in restrained eating (g = 0.35; 95% CI, 0.13 to 0.57; P = .002) and emotional eating behavior (g = 0.32; 95% CI, 0.11 to 0.54; P = .003) and in mental health-related QOL (g = 0.15; 95% CI, 0.07 to 0.22; P
Cognitive bias modification for social anxiety: protocol for a living systematic review of human studies and meta-analysis
Background Social anxiety is a heightened fear and discomfort in social situations. Cases of elevated distress and impaired functioning can lead to a clinical diagnosis of social anxiety disorder. Altering cognitive biases associated with social anxiety has been suggested as potentially beneficial; however, little is known about the comparative effectiveness of such interventions. The aim of this living systematic review is to examine the efficacy of cognitive bias modification for reducing social anxiety. Methods We will search multiple electronic databases for randomised controlled trials evaluating the efficacy of cognitive bias modification for people diagnosed with social anxiety and people exposed to a social stressor. The primary outcome will be change in social anxiety related symptoms; secondary outcomes will be changes in social functioning and quality of life and adverse events. Study selection, data extraction and risk of bias assessment will be done by at least two reviewers using pre-defined tools. We will synthesise data from people with social anxiety diagnosis and those subjected to a simulated social stressor separately using random effects meta-analyses. Heterogeneity will be evaluated by investigating characteristics of included studies and we will conduct a network meta-analysis in order to compare the efficacy of subtypes of cognitive bias modification for social anxiety disorder. We will appraise the strength of the evidence for each outcome by reviewing the overall association, internal and external validity, and reporting biases. Where data allows, we will triangulate the evidence from both sources with a multidisciplinary group of experts. We will also descriptively report factors reported to mediate cognitive bias modification, The review will begin in living mode and the database search will be rerun every three months to identify potential new evidence. We will co-produce this review with members of a global lived experience advisory board. This protocol was registered on 15.10.2024 (CRD42024601380)..
Missed opportunities in early psychosis care: Retrospective chart review of cardiovascular disease monitoring, disengagement and weight changes in a Ghanaian psychiatric hospital
Background Patients with psychosis face an elevated risk of cardiovascular mortality and are more likely to disengage from care. While antipsychotics are essential for treatment, they further increase this risk. Despite this, Ghana lacks a national policy for monitoring cardiovascular risk factors in individuals on antipsychotics. Aims To evaluate disengagement in care and weight changes among newly diagnosed psychotic patients at Accra Psychiatric Hospital, and to inform clinical practice. Method A retrospective review of medical records was conducted for patients newly diagnosed with non-affective psychotic disorders between June 2022 and May 2023. Patients were reviewed for 6 months, with assessments at baseline, 3 months and 6 months. Outcomes included antipsychotic prescription patterns, dropout rates, cardiovascular disease monitoring and weight changes. Descriptive statistics, multinomial logistic regression and linear mixed-effects models were used for analysis. Results The number of patients disengaged from care within the first month was 53.1%, and within 6 months 75.5%; 62.8% received olanzapine at baseline. Weight gain was exponential, with 40% experiencing clinically significant weight gain at 3 months, increasing to 58% at 6 months. Less than 50% of patients had their blood sugar and lipid profiles checked before starting antipsychotics. Higher baseline weight was associated with increased weight over time (β = 0.96, t = 80, P < 0.001, 95% CI 0.93, 0.98). Conclusions High disengagement rates, low cardiovascular disease monitoring and exponential weight gain were observed. Targeted interventions, robust monitoring protocols and further research are needed to improve patient outcomes.
Effects of 28-day simvastatin administration on emotional processing, reward learning, working memory, and salivary cortisol in healthy participants at-risk for depression: OxSTEP, an online experimental medicine trial.
BACKGROUND: Statins are among the most prescribed medications worldwide. Both beneficial (e.g. antidepressant and pro-cognitive) and adverse (e.g. depressogenic and cognitive-impairing) mental health outcomes have been described in clinical studies. The underlying neuropsychological mechanisms, whether positive or negative, are, however, not established. Clarifying such activities has implications for the safe prescribing and repurposing potential of these drugs, especially in people with depression. METHODS: In this double-blind, randomized, placebo-controlled experimental medicine study, we investigated the effects of simvastatin on emotional processing, reward learning, working memory, and waking salivary cortisol (WSC) in 101 people at-risk for depression due to reported high loneliness scores (mean 7.3 ± 1.2 on the UCLA scale). This trial was largely conducted during periods of social distancing due to the COVID-19 pandemic (July 2021-February 2023), and we employed a fully remote design within a UK-wide sample. RESULTS: High retention rates, minimal outlier data, and typical main effects of task condition (e.g. emotion) were seen in all cognitive tasks, indicating this approach was comparable to in-person testing. After 28 days, we found no statistically significant differences (F's 0.20) for any of the measures of emotional processing, reward learning, working memory, and WSC. CONCLUSIONS: Study results do not substantiate concerns regarding adverse neuropsychiatric events due to statins and support the safety of their prescribing in at-risk populations. Although other unmeasured cognitive processes may be involved, our null findings are also in line with more recent clinical evidence suggesting statins do not show antidepressant or pro-cognitive efficacy.
Incentivising participation in mental health app research: lessons learned from a mixed methods randomised controlled trial
Background User engagement is recognised as a critical and pervasive challenge that has limited the potential evidence base being developed for mental health apps. Aim To understand young people’s motivations for participating in a randomised controlled trial for a mental health app and the role of intrinsic (e.g. improving well-being) and extrinsic (e.g. financial incentives) drivers in engagement. Method Emotional Competence for Well-Being (ECoWeB) was a superiority parallel three-arm randomised cohort trial recruiting a cohort of 16–22 year-olds across the UK, Germany, Spain and Belgium, who, depending on risk, were allocated respectively to the PREVENT (n = 1262) versus PROMOTE (n = 2532) trials. We conducted in-depth semi-structured interviews in the UK (n = 18, mean age = 17.7, s.d. = 1.5) and Spain (n = 11, mean age 20.6, s.d. = 1.7) to explore participants’ self-reported motivations and engagement. The trial was registered at ClinicalTrials.gov: NCT04148508. Results Across arms, 21% of participants never set up an account to access the app and approximately 50% did not complete the 3-month follow-up assessment. Engagement was not significantly higher in the intervention arm compared to the control arms across metrics. Qualitative findings demonstrated that although extrinsic factors alone may be enough to prompt someone to sign up to research, intrinsic drivers (e.g. finding the app useful) are needed to ensure longer-term engagement. Conclusions Incentivising participation in clinical trials needs to be consistent with incentives that might be utilised at the point of dissemination and implementation to ensure that findings are replicated if that intervention is adopted at scale.