Rapid Health and Equality Impact Assessment (HEqIA)of Mersey Care NHS Trust’s Outline Business Case for Mental Health and Learning Disability Services

The aim of this assessment is to look at the health and equality impacts of Mersey Care's Outline Business Case which aims to: Establish home treatment as the norm; Refocusing in-patient services around patients who are acutely ill with shorter lengths of stay; Developing a local Psychiatric intensive Care in-patient Unit (PICU); Strengthen community and primary care services. The results of this Health and Equality Impact Assessment will be used to feed the Outline Business Cas

Effects of transcranial direct current stimulation in children and young people with psychiatric disorders: a systematic review.

Transcranial direct current stimulation (tDCS) has demonstrated benefits in adults with various psychiatric disorders, but its clinical utility in children and young people (CYP) remains unclear. This PRISMA systematic review used published and ongoing studies to examine the effects of tDCS on disorder-specific symptoms, mood and neurocognition in CYP with psychiatric disorders. We searched Medline via PubMed, Embase, PsychINFO via OVID, and Clinicaltrials.gov up to December 2022. Eligible studies involved multiple session (i.e., treatment) tDCS in CYP (≤ 25 years old) with psychiatric disorders. Two independent raters assessed the eligibility of studies and extracted data using a custom-built form. Of 33 eligible studies (participant N = 517), the majority (n = 27) reported an improvement in at least one outcome measure of disorder-specific symptoms. Few studies (n = 13) examined tDCS effects on mood and/or neurocognition, but findings were mainly positive. Overall, tDCS was well tolerated with minimal side effects. Of 11 eligible ongoing studies, many are sham-controlled RCTs (n = 9) with better blinding techniques and a larger estimated participant enrolment (M = 79.7; range 15-172) than published studies. Although encouraging, the evidence to date is insufficient to firmly conclude that tDCS can improve clinical symptoms, mood, or cognition in CYP with psychiatric disorders. Ongoing studies appear of improved methodological quality; however, future studies should broaden outcome measures to more comprehensively assess the effects of tDCS and develop dosage guidance (i.e., treatment regimens). [Abstract copyright: © 2023. The Author(s).

An overview of the history and work of Liverpool Public Health Observatory, and its impact on policy and services

Liverpool Public Health Observatory (LPHO) was established in 1990 to provide intelligence to Merseyside Health Authorities (later Primary Care Trusts and now Local Authority Public Health Departments). The work programme for LPHO is now managed by the Cheshire and Merseyside Public Health Intelligence Network, on behalf of the Directors of Public Health. The Intelligence Network identify areas of work based on local priorities and those of the CHAMPS public health collaborative service1. A project lead, usually a member of local authority staff, is identified, and a working group is established – the working group provides expert input into the projects, and a steer to researchers in the University regarding scope and local requirements. Academic support for the projects is provided by the University of Liverpool. When reports are complete, they are uploaded to LPHO’s website, and disseminated widely via CHAMPS to relevant professionals, including relevant leads within the NHS and local authorities, and presented at relevant local, national and international conferences and events. Projects are now evaluated six months after they have been completed. This overview report provides a summary of some of the more recent reports that have been compiled by LPHO, including evaluation findings where these are available, and the impact that LPHO’s work has had on public health practice. An appendix which lists all LPHO’s publications is included at the end of this report for future reference

Direct and mediated effects of a social-emotional and character development program on adolescent substance use

Mitigating and preventing substance use among adolescents requires approaches that address the multitude of factors that influence this behavior. Such approaches must be tested, not only for evidence of empirical effectiveness, but also to determine the mechanisms by which they are successful. The aims of the present study were twofold: 1) To determine the effectiveness of a school-based social-emotional and character development (SECD) program, Positive Action (PA), in reducing substance use (SU) among a sample of U.S. youth living in a low-income, urban environment, and 2) to test one mechanism by which the program achieves its success. We used longitudinal mediation analysis to test the hypotheses that: 1) students attending PA intervention schools engage in significantly less SU than students attending control schools, 2) students attending PA intervention schools show significantly better change in SECD than students attending control schools, and 3) the effect of the PA intervention on SU is mediated by the change in SECD. Analyses revealed program effects on both SECD and SU, a relationship between SECD and SU, and the effects of PA on SU were completely mediated by changes in SECD. Future research directions and implications for schoolbased social-emotional and character development efforts and substance use prevention are addressed.peer-reviewe

Positive allosteric modulation as a potential therapeutic strategy in anti-NMDA receptor encephalitis

N-methyl-d-aspartate receptors (NMDARs) are ionotropic glutamate receptors important for synaptic plasticity, memory, and neuropsychiatric health. NMDAR hypofunction contributes to multiple disorders, including anti-NMDAR encephalitis (NMDARE), an autoimmune disease of the CNS associated with GluN1 antibody-mediated NMDAR internalization. Here we characterize the functional/pharmacological consequences of exposure to CSF from female human NMDARE patients on NMDAR function, and we characterize the effects of intervention with recently described positive allosteric modulators (PAMs) of NMDARs. Incubation (48 h) of rat hippocampal neurons of both sexes in confirmed NMDARE patient CSF, but not control CSF, attenuated NMDA-induced current. Residual NMDAR function was characterized by lack of change in channel open probability, indiscriminate loss of synaptic and extrasynaptic NMDARs, and indiscriminate loss of GluN2B-containing and GluN2B-lacking NMDARs. NMDARs tagged with N-terminal pHluorin fluorescence demonstrated loss of surface receptors. Thus, function of residual NMDARs following CSF exposure was indistinguishable from baseline, and deficits appear wholly accounted for by receptor loss. Coapplication of CSF and PAMs of NMDARs (SGE-301 or SGE-550, oxysterol-mimetic) for 24 h restored NMDAR function following 24 h incubation in patient CSF. Curiously, restoration of NMDAR function was observed despite washout of PAMs before electrophysiological recordings. Subsequent experiments suggested that residual allosteric potentiation of NMDAR function explained the persistent rescue. Further studies of the pathogenesis of NMDARE and intervention with PAMs may inform new treatments for NMDARE and other disorders associated with NMDAR hypofunction.SIGNIFICANCE STATEMENTAnti-N-methyl-d-aspartate receptor encephalitis (NMDARE) is increasingly recognized as an important cause of sudden-onset psychosis and other neuropsychiatric symptoms. Current treatment leaves unmet medical need. Here we demonstrate cellular evidence that newly identified positive allosteric modulators of NMDAR function may be a viable therapeutic strategy.</jats:p

Quinolone Allergy

Quinolones are the second most common antibiotic class associated with drug-induced allergic reactions, but data on quinolone allergy are scarce. This review article discusses the available evidence on quinolone allergy, including prevalence, risk factors, diagnosis, clinical manifestations, cross-reactivity, and management of allergic reactions. Although the incidence of quinolone allergy is still lower than beta-lactams, it has been increasingly reported in recent decades, most likely from its expanded use and the introduction of moxifloxacin. Thorough patient history remains essential in the evaluation of quinolone allergy. Many diagnostic tools have been investigated, but skin tests can yield false-positive results and in vitro tests have not been validated. The drug provocation test is considered the test of choice to confirm a quinolone allergy but is not without risk. Evidence regarding cross-reactivity among the quinolones is limited and conflicting. Quinolone allergy can be manifested either as an immediate or delayed reaction, but is not uniform across the class, with moxifloxacin posing the highest risk of anaphylaxis. Quinolone should be discontinued when an allergic reaction occurs and avoided in future scenarios, but desensitization may be warranted if no alternatives are available

Duplication and Diversification of Dipteran Argonaute Genes, and the Evolutionary Divergence of Piwi and Aubergine

Genetic studies of Drosophila melanogaster have provided a paradigm for RNA interference (RNAi) in arthropods, in which the microRNA and antiviral pathways are each mediated by a single Argonaute (Ago1 and Ago2) and germline suppression of transposable elements is mediated by a trio of Piwi-subfamily Argonaute proteins (Ago3, Aub, and Piwi). Without a suitable evolutionary context, deviations from this can be interpreted as derived or idiosyncratic. Here we analyze the evolution of Argonaute genes across the genomes and transcriptomes of 86 Dipteran species, showing that variation in copy number can occur rapidly, and that there is constant flux in some RNAi mechanisms. The lability of the RNAi pathways is illustrated by the divergence of Aub and Piwi (182-156Ma), independent origins of multiple Piwi-family genes in Aedes mosquitoes (less than 25Ma), and the recent duplications of Ago2 and Ago3 in the tsetse fly Glossina morsitans. In each case the tissue specificity of these genes has altered, suggesting functional divergence or innovation, and consistent with the action of dynamic selection pressures across the Argonaute gene family. We find there are large differences in evolutionary rates and gene turnover between pathways, and that paralogs of Ago2, Ago3, and Piwi/Aub show contrasting rates of evolution after duplication. This suggests that Argonautes undergo frequent evolutionary expansions that facilitate functional divergence.Peer reviewe