Numerous studies have reported high rates of psychosis in the Black Caribbean and Black African populations in the UK. However, few studies have investigated the role of specific risk factors in ...different ethnic groups. We sought to investigate the relationship between long-term separation from, and death of, a parent before the age of 16 and risk of adult psychosis in different ethnic groups.
All patients with a first episode of psychosis who made contact with psychiatric services in defined catchment areas in London and Nottingham, UK and a series of community controls were included in the AESOP (Aetiology and Ethnicity in Schizophrenia and Other Psychoses) study. Data relating to clinical and social variables, including parental separation and loss, were collected from patients and controls.
Separation from, and death of, a parent before the age of 16 were both strongly associated with a two- to threefold increased risk of psychosis. The strength of these associations were similar for White British and Black Caribbean (but not Black African) subjects. Separation from (but not death of) a parent was more common among Black Caribbean controls than White British controls.
Early separation may have a greater impact in the Black Caribbean population, because it is more common, and may contribute to the excess of psychosis in this population.
We extend our established agent-based multiscale computational model of infection of lung tissue by SARS-CoV-2 to include pharmacokinetic and pharmacodynamic models of remdesivir. We model remdesivir ...treatment for COVID-19; however, our methods are general to other viral infections and antiviral therapies. We investigate the effects of drug potency, drug dosing frequency, treatment initiation delay, antiviral half-life, and variability in cellular uptake and metabolism of remdesivir and its active metabolite on treatment outcomes in a simulated patch of infected epithelial tissue. Non-spatial deterministic population models which treat all cells of a given class as identical can clarify how treatment dosage and timing influence treatment efficacy. However, they do not reveal how cell-to-cell variability affects treatment outcomes. Our simulations suggest that for a given treatment regime, including cell-to-cell variation in drug uptake, permeability and metabolism increase the likelihood of uncontrolled infection as the cells with the lowest internal levels of antiviral act as super-spreaders within the tissue. The model predicts substantial variability in infection outcomes between similar tissue patches for different treatment options. In models with cellular metabolic variability, antiviral doses have to be increased significantly (>50% depending on simulation parameters) to achieve the same treatment results as with the homogeneous cellular metabolism.
(1) To determine whether examination under anesthesia (EUA) and/or magnetic resonance imaging (MRI) is an accurate means for determining patient selection for a selective-bundle reconstruction, (2) ...to determine whether the preoperative clinical assessment correlates with the arthroscopic examination, and (3) to examine histologically whether a partial anterior cruciate ligament (ACL) tear is truly partial in terms of vascular insult.
This prospective, nonrandomized cohort study included 95 patients who underwent primary ACL reconstruction from January 2013 through May 2014. All patients underwent an EUA, MRI, and arthroscopic evaluation. In patients with partial ACL tears, the intact bundle was resected and underwent histologic examination. The χ2 test was used to compare EUA and MRI in the detection of partial tears.
Of the 95 patients included, 40 (42%) had EUA findings consistent with a partial ACL tear whereas 22 (23%) had MRI findings interpreted as showing a partial ACL tear. Arthroscopic examination confirmed a partial ACL tear in only 11 patients (12%). The sensitivity of EUA and MRI in the detection of partial ACL tears was 100% and 90.9%, and the specificity was 65% and 85.7%, respectively. The χ2 test suggested statistically significant associations between the method of evaluation and diagnostic outcome χ2(1) = 7.83, P = .005. MRI was 1.24 times more likely to correctly identify a partial tear (95% confidence interval, 1.06-1.45). EUA was 2.23 times as likely to incorrectly identify a partial tear (95% confidence interval, 1.24-4.02). The histologic analysis showed increased numbers of lymphocytes, absent polymorphonuclear leukocytes, predominant fibroblasts, neovascularization, and variable collagen orientation.
There is a disparity between EUA, MRI, and arthroscopic findings in the evaluation of partial ACL tears. Arthroscopy remains the gold standard for diagnosing the macroscopic integrity of the intact bundle. Microscopic analysis reveals that the integrity of the remaining intact ligament material is altered and may show a histologic response similar to a complete ACL rupture.
Level III, prospective, nonrandomized cohort study.
Adolescents and young people (10-24 years old) in the Latin America and the Caribbean (LAC) region represent approximately 25% of the region's population. Since the 2008 global economic crisis, the ...pace of reduction in poverty and income inequality in the LAC region has stalled. The region is characterised by high levels of inequities and is also vulnerable to many natural disasters. Food systems are changing with increased availability and marketing of packaged and fast foods and sugar-sweetened drinks. Adolescence is a formative phase of the life course with multiple physical, emotional and social changes which can make them vulnerable to health problems. We assess the potential impact of macro-determinants, human and economic development as well as income inequality, on 2 top-ranking regional priorities for adolescent nutrition and mental health, using measures of overweight and suicidal ideation and planning which some have shown to be associated.
The Global School-based Health Survey (GSHS) is a nationally representative self-administered, school-based survey. We examined overweight/obesity and suicidal ideation with planning by gross domestic product (GDP) per capita or human development index (HDI) in 10-19-year-old adolescents from 21 LAC countries between 2009 and 2013. Sample sizes varied from 943 in Anguilla to 27,988 in Argentina. A total of 55,295 adolescents had a measure of overweight/obesity status, and 59,061 adolescents reported about suicidal ideation with planning. There was equal representation by sex in the surveys (52% girls and 48% boys). A total of 28.8% of boys and 28.1% of girls had overweight/obesity, and 7.5% of boys and 17.5% of girls reported suicidal ideation with planning over the last 12 months. Adjusted for individual socioeconomic and risk behaviours, and relative to the highest GDP per capita tertile, the middle tertile was associated with 42% (95% confidence interval (CI) 59% to 17%, p = 0.003) and 32% (95% CI 60% to 5%, p = 0.023), and the lowest tertile with 40% (95% CI 55% to 19%, p = 0.001) and 46% (95% CI 59% to 29%, p < 0.001) lower chances of overweight/obesity for girls and boys, respectively. A similar positive effect was seen with HDI, with lowest chances of overweight in the lowest tertile compared with the highest tertile for both sexes. Overweight/obesity was positively related with suicidal ideation with planning for girls (odds ratio (OR) 1.12, 95% CI 1.02 to 1.22, p = 0.009) and weakly related for boys (OR 1.09, 95% CI 0.96 to 1.24, p = 0.182). In contrast to overweight/obesity status, suicidal ideation with planning was not related to macro-level indices despite both outcomes sharing common individual socioeconomic and risk behaviour correlates. Limitations include the dominance of Argentinians in the sample (40%), the exclusion of vulnerable adolescents who dropped out of school, and reporting bias due to stigma of mental health-related issues.
This study shows that economic and human development were positively associated with adolescent overweight/obesity but not with suicidal ideation with planning. We also observed an interconnectedness between overweight/obesity and suicide ideation with planning among girls. These findings highlight the importance of strategies that engage with both upstream and downstream determinants to improve adolescent nutrition and mental health.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A comparison of the transit compartment ordinary differential equation modelling approach to distributed and discrete delay differential equation models is studied by focusing on Quartino’s extension ...to the Friberg transit compartment model of myelosuppression, widely relied upon in the pharmaceutical sciences to predict the neutrophil response after chemotherapy, and on a QSP delay differential equation model of granulopoiesis. An extension to the Quartino model is provided by considering a general number of transit compartments and introducing an extra parameter that allows for the decoupling of the maturation time from the production rate of cells. An overview of the well established linear chain technique, used to reformulate transit compartment models with constant transit rates as distributed delay differential equations (DDEs), is then given. A state-dependent time rescaling of the Quartino model is performed to apply the linear chain technique and rewrite the Quartino model as a distributed DDE, yielding a discrete DDE model in a certain parameter limit. Next, stability and bifurcation analyses are undertaken in an effort to situate such studies in a mathematical pharmacology context. We show that both the original Friberg and the Quartino extension models incorrectly define the mean maturation time, essentially treating the proliferative pool as an additional maturation compartment. This misspecification can have far reaching consequences on the development of future models of myelosuppression in PK/PD.
Neuropsychological investigations can help untangle the aetiological and phenomenological heterogeneity of schizophrenia but have scarcely been employed in the context of treatment-resistant (TR) ...schizophrenia. No population-based study has examined neuropsychological function in the first-episode of TR psychosis.
We report baseline neuropsychological findings from a longitudinal, population-based study of first-episode psychosis, which followed up cases from index admission to 10 years. At the 10-year follow up patients were classified as treatment responsive or TR after reconstructing their entire case histories. Of 145 cases with neuropsychological data at baseline, 113 were classified as treatment responsive, and 32 as TR at the 10-year follow-up.
Compared with 257 community controls, both case groups showed baseline deficits in three composite neuropsychological scores, derived from principal component analysis: verbal intelligence and fluency, visuospatial ability and executive function, and verbal memory and learning (p values⩽0.001). Compared with treatment responders, TR cases showed deficits in verbal intelligence and fluency, both in the extended psychosis sample (t = -2.32; p = 0.022) and in the schizophrenia diagnostic subgroup (t = -2.49; p = 0.017). Similar relative deficits in the TR cases emerged in sub-/sensitivity analyses excluding patients with delayed-onset treatment resistance (p values<0.01-0.001) and those born outside the UK (p values<0.05).
Verbal intelligence and fluency are impaired in patients with TR psychosis compared with those who respond to treatment. This differential is already detectable - at a group level - at the first illness episode, supporting the conceptualisation of TR psychosis as a severe, pathogenically distinct variant, embedded in aberrant neurodevelopmental processes.
The incidence of schizophrenia in the African-Caribbean population in England is reported to be raised. We sought to clarify whether (a) the rates of other psychotic disorders are increased, (b) ...whether psychosis is increased in other ethnic minority groups, and (c) whether particular age or gender groups are especially at risk.
We identified all people (n=568) aged 16-64 years presenting to secondary services with their first psychotic symptoms in three well-defined English areas (over a 2-year period in Southeast London and Nottingham and a 9-month period in Bristol). Standardized incidence rates and incidence rate ratios (IRR) for all major psychosis syndromes for all main ethnic groups were calculated.
We found remarkably high IRRs for both schizophrenia and manic psychosis in both African-Caribbeans (schizophrenia 9.1, manic psychosis 8.0) and Black Africans (schizophrenia 5.8, manic psychosis 6.2) in men and women. IRRs in other ethnic minority groups were modestly increased as were rates for depressive psychosis and other psychoses in all minority groups. These raised rates were evident in all age groups in our study.
Ethnic minority groups are at increased risk for all psychotic illnesses but African-Caribbeans and Black Africans appear to be at especially high risk for both schizophrenia and mania. These findings suggest that (a) either additional risk factors are operating in African-Caribbeans and Black Africans or that these factors are particularly prevalent in these groups, and that (b) such factors increase risk for schizophrenia and mania in these groups.
Initial affective and psychotic reactivity to daily stressors is altered in psychosis, and most notably in early psychosis. In addition to altered initial stress reactivity, results from studies ...using Experience Sampling Methodology (ESM) and psychophysiological measures indicate that impaired recovery from mild stressors may also be a risk factor for mental illness.
The current ESM study investigated affective recovery from daily stressors in chronic psychosis patients (CP; n = 162), individuals at early stages of psychosis (EP; n = 127), and healthy volunteers (HV; n = 220) assessing fluctuations in negative affect (NA), tension, and suspiciousness ten times a day on six consecutive days. Recovery was operationalized for all three variables as the return to baseline (i.e., level at t−1) following the first stressful event of a day (i.e., t0).
The EP group showed a delayed recovery of NA (t1-t3: B = 0.185; p = .007 and B = 0.228; p = .002) and suspiciousness (t1: B = 0.223; p = .010 and B = 0.291; p = .002) compared to HV and CP, respectively. Delayed recovery was detected for tension as well (t1-t2: EP > HV: B = 0.242; p = .040 and EP > CP: B = 0.284; p = .023), but contrary to both other momentary states, this effect disappeared when controlling for subsequent stressful events. There were no significant differences in recovery between HV and CP.
These results suggest that in EP, stressful daily events have longer-lasting effects on overall negative affect and subclinical psychotic-like experiences. Future studies should incorporate physiological and endocrine measures in order to integrate recovery patterns of the different stress systems.
Throughout the SARS-CoV-2 pandemic, several variants of concern (VOCs) have been identified, many of which share recurrent mutations in the spike glycoprotein's receptor-binding domain (RBD). This ...region coincides with known epitopes and can therefore have an impact on immune escape. Protracted infections in immunosuppressed patients have been hypothesized to lead to an enrichment of such mutations and therefore drive evolution towards VOCs. Here, we present the case of an immunosuppressed patient that developed distinct populations with immune escape mutations throughout the course of their infection. Notably, by investigating the co-occurrence of substitutions on individual sequencing reads in the RBD, we found quasispecies harboring mutations that confer resistance to known monoclonal antibodies (mAbs) such as S:E484K and S:E484A. These mutations were acquired without the patient being treated with mAbs nor convalescent sera and without them developing a detectable immune response to the virus. We also provide additional evidence for a viral reservoir based on intra-host phylogenetics, which led to a viral substrain that evolved elsewhere in the patient's body, colonizing their upper respiratory tract (URT). The presence of SARS-CoV-2 viral reservoirs can shed light on protracted infections interspersed with periods where the virus is undetectable, and potential explanations for long-COVID cases.
During the SARS-CoV-2 global pandemic, several vaccines, including mRNA and adenovirus vector approaches, have received emergency or full approval. However, supply chain logistics have hampered ...global vaccine delivery, which is impacting mass vaccination strategies. Recent studies have identified different strategies for vaccine dose administration so that supply constraints issues are diminished. These include increasing the time between consecutive doses in a two-dose vaccine regimen and reducing the dosage of the second dose. We consider both of these strategies in a mathematical modeling study of a non-replicating viral vector adenovirus vaccine in this work. We investigate the impact of different prime-boost strategies by quantifying their effects on immunological outcomes based on simple system of ordinary differential equations. The boost dose is administered either at a standard dose (SD) of 1000 or at a low dose (LD) of 500 or 250 vaccine particles. Results show dose-dependent immune response activity. Our model predictions show that by stretching the prime-boost interval to 18 or 20, in an SD/SD or SD/LD regimen, the minimum promoted antibody (Nab) response will be comparable with the neutralizing antibody level measured in COVID-19 recovered patients. Results also show that the minimum stimulated antibody in SD/SD regimen is identical with the high level observed in clinical trial data. We conclude that an SD/LD regimen may provide protective capacity, which will allow for conservation of vaccine doses.
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