Little is known about patients with a first episode of psychosis (FEP) who had first presented to prodromal services with an "at risk mental state" (ARMS) before making the transition to psychosis. ...We set out to identify the proportion of patients with a FEP who had first presented to prodromal services in the ARMS state, and to compare these FEP patients with FEP patients who did not have prior contact with prodromal services.
In this study information on 338 patients aged ≤37 years who presented to mental health services between 2010 and 2012 with a FEP was examined. The data on pathways to care, clinical and socio-demographic characteristics were extracted from the Biomedical Research Council Case Register for the South London and Maudsley NHS Trust.
Over 2 years, 14 (4.1% of n = 338) young adults presented with FEP and had been seen previously by the prodromal services. These ARMS patients were more likely to enter their pathway to psychiatric care via referral from General Practice, be born in the UK and to have had an insidious mode of illness onset than FEP patients without prior contact with the prodromal services.
In the current pathways to care configuration, prodromal services are likely to prevent only a few at-risk individuals from transitioning to psychosis even if effective preventative treatments become available.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Renin-angiotensin aldosterone system inhibitors (RAASi) are commonly used among patients hospitalized with a severe acute respiratory syndrome coronavirus 2 infection coronavirus disease 2019 ...(COVID-19). We evaluated whether continuation versus discontinuation of RAASi were associated with short term clinical or biochemical outcomes.
The RAAS-COVID-19 trial was a randomized, open label study in adult patients previously treated with RAASi who are hospitalized with COVID-19 (NCT04508985). Participants were randomized 1:1 to discontinue or continue RAASi. The primary outcome was a global rank score calculated from baseline to day 7 (or discharge) incorporating clinical events and biomarker changes. Global rank scores were compared between groups using the Wilcoxon test statistic and the negative binomial test (using incident rate ratio IRR) and the intention-to-treat principle.
Overall, 46 participants were enrolled; 21 participants were randomized to discontinue RAASi and 25 to continue. Patients’ mean age was 71.5 years and 43.5% were female. Discontinuation of RAASi, versus continuation, resulted in a non-statistically different mean global rank score (discontinuation 6 standard deviation SD 6.3 vs continuation 3.8 (SD 2.5); P = .60). The negative binomial analysis identified that discontinuation increased the risk of adverse outcomes (IRR 1.67 95% CI 1.06-2.62; P = .027); RAASi discontinuation increased brain natriuretic peptide levels (% change from baseline: +16.7% vs -27.5%; P = .024) and the incidence of acute heart failure (33% vs 4.2%, P = .016).
RAASi continuation in participants hospitalized with COVID-19 appears safe; discontinuation increased brain natriuretic peptide levels and may increase risk of acute heart failure; where possible, RAASi should be continued.
People with mental disorders and intellectual disabilities experience excess mortality compared with the general population. The impact of COVID-19 on exacerbating this, and in widening ethnic ...inequalities, is unclear.
Prospective data (N=167,122) from a large mental healthcare provider in London, UK, with deaths from 2019 to 2020, used to assess age- and gender-standardised mortality ratios (SMRs) across nine psychiatric conditions (schizophrenia-spectrum disorders, affective disorders, somatoform/ neurotic disorders, personality disorders, learning disabilities, eating disorders, substance use disorders, pervasive developmental disorders, dementia) and by ethnicity.
Prior to the World Health Organization (WHO) declaring COVID-19 a public health emergency on 30th January 2020, all-cause SMRs across all psychiatric cohorts were more than double the general population. By the second quarter of 2020, when the UK experienced substantial peaks in COVID-19 deaths, all-cause SMRs increased further, with COVID-19 SMRs elevated across all conditions (notably: learning disabilities: SMR: 9.24 (95% CI: 5.98-13.64), pervasive developmental disorders: 5.01 (95% CI: 2.40-9.20), eating disorders: 4.81 (95% CI: 1.56-11.22), schizophrenia-spectrum disorders: 3.26 (95% CI: 2.55-4.10), dementia: 3.82 (95% CI: 3.42, 4.25) personality disorders 4.58 (95% CI: 3.09-6.53)). Deaths from other causes remained at least double the population average over the whole year. Increased SMRs were similar across ethnic groups.
People with mental disorders and intellectual disabilities were at a greater risk of deaths relative to the general population before, during and after the first peak of COVID-19 deaths, with similar risks by ethnicity. Mortality from non-COVID-19/ other causes was elevated before/ during the pandemic, with higher COVID-19 mortality during the pandemic.
ESRC (JD, CM), NIHR (JD, RS, MH), Health Foundation (JD), GSK, Janssen, Takeda (RS).
Abstract Recent research conducted in high-income countries suggests psychotic experiences are common in the general population, but evidence from low- and middle-income countries (LMIC) remains ...limited. Sri Lanka is a LMIC affected by three decades of civil conflict and, in 2004, a devastating tsunami. This study aimed to investigate the prevalence of psychotic experiences in a general population sample in Sri Lanka and associations with conflict- and tsunami-related trauma. This is a first National Mental Health Survey conducted in Sri Lanka. A cross-sectional, multi-stage, cluster sampling design was used to estimate the prevalence of psychotic symptoms. Data on socio-demographic characteristics, conflict- and tsunami-related trauma, and psychotic experiences were collected using culturally validated measures in a sample of 5927 participants. The weighted prevalence of psychotic symptoms was 9.7%. Exposure to one or more conflict-related events (adj. OR 1.79, 95% CI 1.40–2.31, p < 0.001) and loss or injury of a family member or friend through conflict (adj. OR, 1.83, 95% CI 1.42–2.37, p < 0.001) were associated with increased odds of reporting psychotic experiences. Psychotic experiences were more common in individuals directly exposed to tsunami disaster (adj. OR, 1.68, 95% CI 1.04–2.73, P = 0.035) and in those who had a family member who died or was injured as result of tsunami (adj. OR, 1.42, 95% CI 1.04–1.94, p = 0.029). Our findings suggest that psychotic experiences are common in the Sri Lankan population. Exposure to traumatic events in armed conflicts and natural disasters may be important socio-environmental factors in the development of psychotic experiences.
Excess mortality in severe mental illness (defined here as schizophrenia, schizoaffective disorders, and bipolar affective disorders) is well described, but little is known about this inequality in ...ethnic minorities. We aimed to estimate excess mortality for people with severe mental illness for five ethnic groups (white British, black Caribbean, black African, south Asian, and Irish) and to assess the association of ethnicity with mortality risk.
We conducted a longitudinal cohort study of individuals with a valid diagnosis of severe mental illness between Jan 1, 2007, and Dec 31, 2014, from the case registry of the South London and Maudsley Trust (London, UK). We linked mortality data from the UK Office for National Statistics for the general population in England and Wales to our cohort, and determined all-cause and cause-specific mortality by ethnicity, standardised by age and sex to this population in 2011. We used Cox proportional hazards regression to estimate hazard ratios and a modified Cox regression, taking into account competing risks to derive sub-hazard ratios, for the association of ethnicity with all-cause and cause-specific mortality.
We identified 18 201 individuals with a valid diagnosis of severe mental illness (median follow-up 6·36 years, IQR 3·26–9·92), of whom 1767 died. Compared with the general population, age-and-sex-standardised mortality ratios (SMRs) in people with severe mental illness were increased for a range of causes, including suicides (7·65, 95% CI 6·43–9·04), non-suicide unnatural causes (4·01, 3·34–4·78), respiratory disease (3·38, 3·04–3·74), cardiovascular disease (2·65, 2·45–2·86), and cancers (1·45, 1·32–1·60). SMRs were broadly similar in different ethnic groups with severe mental illness, although the south Asian group had a reduced SMR for cancer mortality (0·49, 0·21–0·96). Within the cohort with severe mental illness, hazard ratios for all-cause mortality and sub-hazard ratios for natural-cause and unnatural-cause mortality were lower in most ethnic minority groups relative to the white British group.
People with severe mental illness have excess mortality relative to the general population irrespective of ethnicity. Among those with severe mental illness, some ethnic minorities have lower mortality than the white British group, for which the reasons deserve further investigation.
UK Health Foundation and UK Academy of Medical Sciences.
In the UK, around 5% of 11-16-year olds experience conduct problems of clinical importance. However, there are limited data on prevalence of conduct problems by ethnic group, and how putative social ...risk factors may explain any variations in prevalence. This study has two main aims: (1) to estimate the prevalence and nature of conduct problems overall, and by ethnic group and gender, among adolescents in diverse inner-city London schools; (2) to assess the extent to which putative risk factors - racial discrimination, socioeconomic status, parental control, and troublesome friends - explain any observed differences in prevalence of conduct problems between ethnic groups.
This study uses baseline data from REACH, an accelerated cohort study of adolescent mental health in inner-city London. Self-report questionnaire data were collected on conduct problems and a range of distinct putative social risk factors (including racial discrimination, free school meals, troublesome friends, and parental care and control). A total of 4353 pupils, 51% girls, aged 11-14 participated. We estimated prevalence of conduct problems and used multilevel logistic regression to examine differences by ethnicity and gender and associations with putative risk factors.
Prevalence of conduct problems in inner-city schools was around three times higher than reported in national studies (i.e., 16% 95%CI: 15·2-17·5 vs. 5% 95%CI 4·6-5·9). Compared with overall prevalence, conduct problems were lower among Indian/Pakistani/Bangladeshi (RR: 0.53 95% CI:0.31-0.87) and white British (RR: 0.65 0.51-0.82) groups, and higher among black Caribbean (RR: 1.39 95%CI:1.19-1.62) and mixed white and black (RR: 1.29 95% CI: 1.02-1.60) groups. Risk of conduct problems was higher among those who were exposed to racial discrimination compared with those who were not (RR: 1.95 95% CI: 1.59-2.31).
Conduct problems are markedly more common in inner-city schools, and variations in the prevalence of conduct problems are, to some extent, rooted in modifiable social contexts and experiences, such as experiences of racial discrimination.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mathematical modeling has made significant contributions to drug design, development, and optimization. Virtual clinical trials that integrate mathematical models to explore patient heterogeneity and ...its impact on a variety of therapeutic questions have recently risen in popularity. Here, we outline best practices for creating virtual patients from mathematical models to ultimately implement and execute a virtual clinical trial. In this practical guide, we discuss and provide examples of model design, parameter estimation, parameter sensitivity, model identifiability, and virtual patient cohort creation. Our goal is to help researchers adopt these approaches to further the use of virtual population-based analysis and virtual clinical trials.
We use the McKendrick equation with variable ageing rate and randomly distributed mat-uration time to derive a state dependent distributed delay differential equation. We show that the resulting ...delay differential equation preserves non-negativity of initial conditions and we characterise local stability of equilibria. By specifying the distribution of maturation age, we recover state depen-dent discrete, uniform and gamma distributed delay differential equations. We show how to reduce the uniform case to a system of state dependent discrete delay equations and the gamma distributed case to a system of ordinary differential equations. To illustrate the benefits of these reductions, we convert previously published transit compartment models into equivalent distributed delay differential equations.
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