Emergency Department presentations with suicidal ideation: A missed opportunity for intervention?

Objectives Suicidal ideation constitutes a central element of most theories of suicide. Despite its prevalence, most research has focused on other suicidal behaviours such as self-harm. This study examines the characteristics of those presenting to EDs with suicidal ideation and quantifies the associated risk of suicide and other causes of death. Methods This retrospective cohort study used population-wide health administration data linked to data from the Northern Ireland Registry of Self-Harm and centrally held mortality records from April 2012 to December 2019. Mortality data, coded as suicide, all-external causes and all-cause mortality was analysed using Cox proportional hazards. Additional cause-specific analyses included accidental deaths, deaths from natural causes, and drug and alcohol-related causes. Results The final cohort comprised 1,662,118 individuals aged over 10 years, of whom 15,267 presented to the ED with ideation during the study period. Individuals with ideation had a ten-fold increased risk of death from suicide (HRadj=10.84, 95% CI 9.18, 12.80) and from all external causes (HRadj=10.65, 95% CI 9.66, 11.74) and a three-fold risk of death from all causes (HRadj= 3.01, 95% CI 2.84, 3.20). Further cause-specific analyses indicated that risk of accidental death (HRadj=8.24, 95% CI 6.29, 10.81), alcohol-related death (HRadj=10.57, 95% CI 9.07, 12.31), and drug-related death (HRadj=15.17, 95% CI 11.36, 20.26) were also significantly raised. There were few socio-demographic and economic characteristics that would identify which of these patients are most at risk of suicide or other causes of death. Conclusions The identification of those experiencing ideation is recognised to be important yet difficult in practice. The ED represents an important potential intervention point for this hard-to-reach population. However, and unlike those presenting with self-harm, clinical guidelines for the management and recommended best practice and care of these individuals are lacking

Characterization of a murine mixed neuron-glia model and cellular responses to regulatory T cell-derived factors

Abstract One of the unmet clinical needs in demyelinating diseases such as Multiple Sclerosis (MS) is to provide therapies that actively enhance the process of myelin regeneration (remyelination) in the central nervous system (CNS). Oligodendrocytes, the myelinating cells of the CNS, play a central role in remyelination and originate from oligodendrocyte progenitor cells (OPCs). We recently showed that depletion of regulatory T cells (Treg) impairs remyelination in vivo, and that Treg-secreted factors directly enhance oligodendrocyte differentiation. Here we aim to further characterize the dynamics of Treg-enhanced oligodendrocyte differentiation as well as elucidate the cellular components of a murine mixed neuron-glia model. Murine mixed neuron-glia cultures were generated from P2–7 C57BL/6 mice and characterized for percentage of neuronal and glial cell populations prior to treatment at 7 days in vitro (div) as well as after treatment with Treg-conditioned media at multiple timepoints up to 12 div. Mixed neuron-glia cultures consisted of approximately 30% oligodendroglial lineage cells, 20% neurons and 10% microglia. Furthermore, a full layer of astrocytes, that could not be quantified, was present. Treatment with Treg-conditioned media enhanced the proportion of MBP+ oligodendrocytes and decreased the proportion of PDGFRα+ OPCs, but did not affect OPC proliferation or survival. Treg-enhanced oligodendrocyte differentiation was not caused by Treg polarizing factors, was dependent on the number of activation cycles Treg underwent and was robustly achieved by using 5% conditioned media. These studies provide in-depth characterization of a murine mixed neuron-glia model as well as further insights into the dynamics of Treg-enhanced oligodendrocyte differentiation

Hospital-presenting self-harm and ideation: Comparison of incidence, profile and risk of repetition

Objective: The aim of this study was to describe presentations to hospital as a result of self-harm or suicidal ideation and to examine patterns of repetition. Method: Presentations made to hospital emergency departments in Northern Ireland following self-harm and ideation between April 2012 and March 2017 were recorded by the Northern Ireland Registry of Self-harm. Person-based rates per 100,000 were calculated using national population estimates. Risk of repeat attendance to hospital was examined using Kaplan-Meier analyses. Results: A total of 62,213 presentations to emergency departments following self-harm or with ideation were recorded. The rate of self-harm was more than twice the rate of hospital-presenting ideation. Rates of ideation were higher among men, and both self-harm and ideation rates peaked for girls aged 15–19 and men aged 20–24 years. The cumulative probability of repeat attendance to hospital was higher following ideation (52% after 12 months), primarily because 12% of ideation presentations were followed by a subsequent self-harm presentation, whereas 4% of self-harm presentations were followed by ideation. Conclusions: Our findings indicate that hospital presenters with ideation are at high risk of future self-harm. The transition from ideation to suicidal behaviour is important to consider and research could inform effective and early intervention measures

Suicide risk following Emergency Department presentation with self-harm varies by hospital

Objectives A large proportion of those who die by suicide present to an Emergency Department (ED) with self-harm (SH) in the year before death. This study examines ‘does risk of death following ED presentation with SH vary according to hospital attended?’ Methods The Northern Ireland Self-Harm Registry provided data on SH presentations to 12 ED departments in NI between 2012-2019. Linkage to health and mortality records provided follow up to December 2019. Cox proportional hazards regression models were employed to assess mortality risk following presentation with SH among 12 ED departments in NI. Results Analysis of the 64,350 ED presentations for self-harm by 30,011 individuals confirmed a marked variation across EDs in proportion of patients receiving mental health assessment and likelihood of admission to general and psychiatric wards. There was a significant variation in suicide risk according to ED attended with the three-fold range between the lowest (HRadj 0.32 95%CIs 0.16, 0.67) and highest. These differences persisted even after adjustment for patient characteristics, variation in types of self-harm, and care management at the ED. Conclusion Management of SH cases in the ED is important, however, it is the availability, access and level of engagement with, care in the community rather than the immediate care at EDs that is most critical for patients presenting to ED with self-harm

What happens after self-harm? An exploration of self-harm and suicide using the Northern Ireland Registry of Self-Harm

Background Suicide is a major public health concern and Northern Ireland (NI) has the highest rate of both self-harm and suicide in the UK and Ireland. In order to target prevention strategies effectively, it is vital to understand who is most at risk. Aim To explore the risk factors for completed suicide following presentation with self-harm. Methods The Northern Ireland Registry of Self-Harm (NIRSH) collects information on all self-harm and suicide ideation presentations to all Emergency Departments in NI. NIRSH data from 2012-2015 was linked to centralised electronic data relating to primary care, prescribed medication and mortality records. Logistic regression was employed to quantify the likelihood of mortality with adjustment for factors associated with mental ill health and suicide risk, and Cox regression was used to explore which characteristics of those who self-harm are most associated with risk of suicide. Results The cohort consisted of all 1,483,435 individuals born or resident in NI from 1st January 1970 until 31st December 2015 (maximum age in 2015, 45 years). During the follow-up period, 12,327 (0.8%) individuals presented with self-harm and 892 (0.1%) died by suicide. Rates of self-harm were equivalent for males and females with highest rates observed in the 18-24 years age group, and more common in deprived than affluent areas (OR=3.42, 95%CI 3,21, 3.65). Most individuals self-harmed via self-poisoning with psychotropic medications (71.5%), followed by self-injury with a sharp object (21.7%). Although only 162 (1.3%) of those who presented with self-harm went on to die by suicide, those who presented with self-harm were 24 times more likely to die by suicide compared to those who did not present with self-harm after adjustment for age and sex (HR=24.3, 95%CI 20.46,28.76). Conclusion This constitutes the first population-wide study of self-harm in the UK and could be utilised to inform suicide prevention strategies. Background Suicide is a major public health concern and Northern Ireland (NI) has the highest rate of both self-harm and suicide in the UK and Ireland. In order to target prevention strategies effectively, it is vital to understand who is most at risk

Regulatory T cells promote myelin regeneration in the central nervous system

Regeneration of CNS myelin involves differentiation of oligodendrocytes from oligodendrocyte progenitor cells. In multiple sclerosis, remyelination can fail despite abundant oligodendrocyte progenitor cells, suggesting impairment of oligodendrocyte differentiation. T cells infiltrate the CNS in multiple sclerosis, yet little is known about T cell functions in remyelination. We report that regulatory T cells (T$_{reg}$) promote oligodendrocyte differentiation and (re)myelination. T$_{reg}$-deficient mice exhibited substantially impaired remyelination and oligodendrocyte differentiation, which was rescued by adoptive transfer of T$_{reg}$. In brain slice cultures, T$_{reg}$ accelerated developmental myelination and remyelination, even in the absence of overt inflammation. T$_{reg}$ directly promoted oligodendrocyte progenitor cell differentiation and myelination in vitro. We identified CCN3 as a T$_{reg}$-derived mediator of oligodendrocyte differentiation and myelination in vitro. These findings reveal a new regenerative function of T$_{reg}$ in the CNS, distinct from immunomodulation. Although the cells were originally named 'T$_{reg}$' to reflect immunoregulatory roles, this also captures emerging, regenerative T$_{reg}$ functions.This work was supported by the Biotechnology and Biological Sciences Research Council (BB/J01026X/1 and BB/N003721/1, to D.C.F.), The Leverhulme Trust (ECF-2014-390, to Y.D.), QUB (QUB - Lucy McGuigan Bequest, to D.C.F.), The UK Multiple Sclerosis Society (941 and 50, to R.J.M.F. and C.Z.), MRC UK Regenerative Medicine platform (MR/KO26666/1, to A.C.W.), University of Edinburgh Wellcome Trust Multi User Equipment Grant (WT104915MA, to A.C.W.), by a core support grant from the Wellcome Trust and MRC to the Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute (097922/Z/11/Z to R.J.M.F.), studentship support from Dept. for the Economy (Northern Ireland) and British Pathological Society, US National Multiple Sclerosis Society (RG5203A4, to J.R.C.), NIH/NINDS (NS095889, to J.R.C.), NIH/NIGMS IRACDA Postdoctoral Fellowship (K12GM081266, to S.R.M.) and Wellcome Trust (110138/Z/15/Z, to D.C.F.)

The Journey

Jacirama is a native Amazonian Indian who lives with his isolated tribe of Ibiajara in the Amazon rainforest. He is a young shaman’s apprentice and is fascinated with plant lore and medicinal cures, an innate ability he was born with. He has always been a bit different. His skin is prone to burning from the sun; his eyes are the colour of the sky. This enigma was passed off to him by the chief and shamans as a gift from the gods, born under the moon - jaci, he was given the name Jacirama. One day while walking through the forest with his mother, they encounter some strangers, white men. He is suspicious of them, as he has been taught to be from myths told around the fireside at night by the elders. He notices their pale skin and is shocked to see his own blue eyes reflected back at him in a stranger. When he questions his mother, he learns the truth. He had always thought he had come from a long line of shamans and was deeply proud of his heritage. Now this knowledge has been wiped out. He is disgusted to find that he is not of pure Tupi-guarani blood. He learns that his father was a travelling Ethno-botanist named Jerry who stayed with the tribe twenty-two years earlier. Theirs was a quick union of passion and mutual attraction when she was young and unmarried. Jacirama suddenly felt as if he didn’t belong, in his own skin or in the tribe. He must leave, to find his father, to find out where he comes from. He feels he cannot truly know himself until he does. He leaves the tribe in search of his father; with only the names his mother has given him as clues, Jerry and Boston. This tale is of his journey. The exegesis studies the motivation behind this creative work and analyses wider global issues that it may raise, including the importance of the Amazon rainforest as a source of undiscovered medicinal cures, and the necessity for the preservation of the rainforest and indigenous populations. It analyses the overriding question in the novel, that of “who am I?” The exegisis identifies ethnic hybridity studies to demonstrate the importance of knowing ones own cultural identity in order to promote, amongst other benefits, enhanced self esteem

An Insight

Jacirama is a native Amazonian Indian who lives with his isolated tribe of Ibiajara in the Amazon rainforest. He is a young shaman’s apprentice and is fascinated with plant lore and medicinal cures, an innate ability he was born with. He has always been a bit different. His skin is prone to burning from the sun; his eyes are the colour of the sky. This enigma was passed off to him by the chief and shamans as a gift from the gods, born under the moon - jaci, he was given the name Jacirama. One day while walking through the forest with his mother, they encounter some strangers, white men. He is suspicious of them, as he has been taught to be from myths told around the fireside at night by the elders. He notices their pale skin and is shocked to see his own blue eyes reflected back at him in a stranger. When he questions his mother, he learns the truth. He had always thought he had come from a long line of shamans and was deeply proud of his heritage. Now this knowledge has been wiped out. He is disgusted to find that he is not of pure Tupi-guarani blood. He learns that his father was a travelling Ethno-botanist named Jerry who stayed with the tribe twenty-two years earlier. Theirs was a quick union of passion and mutual attraction when she was young and unmarried. Jacirama suddenly felt as if he didn’t belong, in his own skin or in the tribe. He must leave, to find his father, to find out where he comes from. He feels he cannot truly know himself until he does. He leaves the tribe in search of his father; with only the names his mother has given him as clues, Jerry and Boston. This tale is of his journey. The exegesis studies the motivation behind this creative work and analyses wider global issues that it may raise, including the importance of the Amazon rainforest as a source of undiscovered medicinal cures, and the necessity for the preservation of the rainforest and indigenous populations. It analyses the overriding question in the novel, that of “who am I?” The exegisis identifies ethnic hybridity studies to demonstrate the importance of knowing ones own cultural identity in order to promote, amongst other benefits, enhanced self esteem