Axonal response of mitochondria to demyelination and complex IV activity within demyelinated axons in experimental models of multiple sclerosis.

AIMS: Axonal injury in multiple sclerosis (MS) and experimental models is most frequently detected in acutely demyelinating lesions. We recently reported a compensatory neuronal response, where mitochondria move to the acutely demyelinated axon and increase the mitochondrial content following lysolecithin-induced demyelination. We termed this homeostatic phenomenon, which is also evident in MS, the axonal response of mitochondria to demyelination (ARMD). The aim of this study is to determine whether ARMD is consistently evident in experimental demyelination and how its perturbation relates to axonal injury. METHODS: In the present study, we assessed axonal mitochondrial content as well as axonal mitochondrial respiratory chain complex IV activity (cytochrome c oxidase or COX) of axons and related these to axonal injury in nine different experimental disease models. We used immunofluorescent histochemistry as well as sequential COX histochemistry followed by immunofluorescent labelling of mitochondria and axons. RESULTS: We found ARMD a consistent and robust phenomenon in all experimental disease models. The increase in mitochondrial content within demyelinated axons, however, was not always accompanied by a proportionate increase in complex IV activity, particularly in highly inflammatory models such as experimental autoimmune encephalomyelitis (EAE). Axonal complex IV activity inversely correlated with the extent of axonal injury in experimental disease models. CONCLUSIONS: Our findings indicate that ARMD is a consistent and prominent feature and emphasise the importance of complex IV activity in the context of ARMD, especially in autoimmune inflammatory demyelination, paving the way for the development of novel neuroprotective therapies.

Key issues, challenges, and preferred supports for those bereaved by suicide: Insights from postvention experts.

For many, suicide bereavement is challenging. Postvention responses are few and evidence to inform them is lacking. Eighteen postvention experts completed an online survey regarding the key issues, challenges, and supports available to people bereaved by suicide. Participants were asked to identify the issues, then rank them in terms of importance at key times during the first 2 years after death, with navigating grief, managing relationships, and dealing with practical challenges identified. Access to information, practical assistance and non-judgmental support were most important early in the bereavement period. These findings provide a foundation for recommendations for postvention interventions.

Hospital-treated deliberate self-poisoning patients: Drug-induced delirium and clinical outcomes.

OBJECTIVE: Drug-induced delirium has been attributed to opioid, benzodiazepine, antipsychotic, antihistaminic and anticholinergic drug groups at therapeutic doses. Delirium also occurs in hospital-treated self-poisoning (at supra-therapeutic doses), although the causative drug classes are not well established and co-ingestion is common. We tested the magnitude and direction of association of five major drug groups with incident cases of delirium. METHODS: A retrospective longitudinal cohort (n = 5131) study was undertaken of deliberate and recreational/chronic misuse poisoning cases from a regional sentinel toxicology unit. We described ingestion and co-ingestion patterns and estimated the unadjusted and adjusted odds for developing a drug-induced delirium. We also estimated the odds of drug-induced delirium being associated with three outcomes: intensive care unit admission, general hospital length of stay and discharge to home. RESULTS: Drug-induced delirium occurred in 3.9% of cases (n = 200). The unadjusted odds ratios for development of delirium were increased for anticholinergics 10.79 (5.43-21.48), antihistamines 6.10 (4.20-8.84) and antipsychotics 2.99 (2.20-4.06); non-significant for opioids 1.31 (95% confidence interval = [0.81, 2.13]); and reduced for benzodiazepines 0.37 (0.24-0.58); with little change after adjustment for age, gender and co-ingestion. Delirium was associated with intensive care unit admission, longer length of stay and discharge destination. CONCLUSION: Drug-induced delirium was uncommon in this population. Co-ingestion was common but did not alter the risk. In contrast to drug-induced delirium at therapeutic doses in older populations, opioids were not associated with delirium and benzodiazepines were protective. Drug-induced delirium required increased clinical services. Clinical services should be funded and prepared to provide additional supportive care for these deliriogenic drug group ingestions.

Comparison of accredited person and medical officer discharge decisions under the Mental Health Act of NSW: A cohort study of deliberate self-poisoning patients.

BACKGROUND: The Accredited Persons Programme was introduced in 2003. The relevant Mental Health Acts (NSW) authorised reviews by appropriately credentialed non-medical health professionals as part of the process of detaining and treating a person without consent: an authority previously held by medical officers. Evaluations of the Programme are needed. OBJECTIVE: To compare discharge decisions for hospital-treated deliberate self-poisoning patients made by an Accredited Person and Medical Officers. METHODS: For a 10-year cohort (2003-2012) of index hospital-treated deliberate self-poisoning admissions at the Calvary Mater Newcastle, we compared Accredited Person and Medical Officer discharge decisions from the general hospital. We specifically examined discharges to the psychiatric hospital under a Mental Health Act certificate (used as an index of the Accredited Person's use of the authority under the Accredited Persons Programme) compared to any other discharge destination. Unadjusted and adjusted logistic regression models and a propensity score analysis were used to explore the relationship between clinician type and discharge destination. RESULTS: There were 2237 index assessments (Accredited Person = 884; Medical Officer = 1443). One-quarter (27%) were referred for assessment under the Act at the psychiatric hospital, with the Accredited Person significantly more likely (32%) to require this compared to the Medical Officers (24%); Risk Difference: 8.3% (4.5 to 12.1). However, after adjusting for patient characteristics; Risk Difference: -3.0% (-5.9 to -0.1) and for propensity score, Risk Difference: -3.3% (-6.7 to 0.1), the Accredited Person and Medical Officer likelihood of discharging for an assessment under the Act was similar. CONCLUSIONS: The Accredited Person assessed more clinically complex patients than the Medical Officers. After adjusting for clinical complexity and propensity score, the likelihood of referral for involuntary psychiatric hospital care was similar for Accredited Person and Medical Officers. Our evaluation of the Accredited Person programme in the general hospital was favourable, and wider implementation and evaluation is warranted.

Effectiveness of Brief Contact Interventions for Bereavement: A Systematic Review.

Brief contact interventions are an efficient and cost-effective way of providing support to individuals. Whether they are an effective bereavement intervention is not clear. This systematic review included articles from 2014 to 2021.711 studies were identified, with 15 meeting inclusion criteria. The brief contact interventions included informational and emotional supports. Narrative synthesis identified that participants valued brief contact interventions, however some did not find them helpful. Exposure to a brief contact intervention was typically associated with improvements in wellbeing. Studies with comparison groups typically found significant but modest improvements in grief, depression symptoms and wellbeing associated with the intervention. However, one intervention was associated with significant deterioration of depression symptoms. Existing brief contact interventions for bereavement appear feasible, generally acceptable to the target population and are associated with improvements in wellbeing. Further development and evaluation to account for why improvements occur, and to identify any unintended impacts, is required.

Enhanced axonal response of mitochondria to demyelination offers neuroprotection: implications for multiple sclerosis.

Axonal loss is the key pathological substrate of neurological disability in demyelinating disorders, including multiple sclerosis (MS). However, the consequences of demyelination on neuronal and axonal biology are poorly understood. The abundance of mitochondria in demyelinated axons in MS raises the possibility that increased mitochondrial content serves as a compensatory response to demyelination. Here, we show that upon demyelination mitochondria move from the neuronal cell body to the demyelinated axon, increasing axonal mitochondrial content, which we term the axonal response of mitochondria to demyelination (ARMD). However, following demyelination axons degenerate before the homeostatic ARMD reaches its peak. Enhancement of ARMD, by targeting mitochondrial biogenesis and mitochondrial transport from the cell body to axon, protects acutely demyelinated axons from degeneration. To determine the relevance of ARMD to disease state, we examined MS autopsy tissue and found a positive correlation between mitochondrial content in demyelinated dorsal column axons and cytochrome c oxidase (complex IV) deficiency in dorsal root ganglia (DRG) neuronal cell bodies. We experimentally demyelinated DRG neuron-specific complex IV deficient mice, as established disease models do not recapitulate complex IV deficiency in neurons, and found that these mice are able to demonstrate ARMD, despite the mitochondrial perturbation. Enhancement of mitochondrial dynamics in complex IV deficient neurons protects the axon upon demyelination. Consequently, increased mobilisation of mitochondria from the neuronal cell body to the axon is a novel neuroprotective strategy for the vulnerable, acutely demyelinated axon. We propose that promoting ARMD is likely to be a crucial preceding step for implementing potential regenerative strategies for demyelinating disorders.

Hospital-treated deliberate self-poisoning in the older adult: Identifying specific clinical assessment needs.

BACKGROUND: Hospital-treated deliberate self-poisoning is common, with a median patient age of around 33 years. Clinicians are less familiar with assessing older adults with self-poisoning and little is known about their specific clinical requirements. OBJECTIVE: To identify clinically important factors in the older-age population by comparing older adults (65+ years) with middle-aged adults (45-64 years) during an index episode of hospital-treated deliberate self-poisoning. METHODS: A prospective, longitudinal, cohort study of people presenting to a regional referral centre for deliberate self-poisoning (Calvary Mater Newcastle, Australia) over a 10-year period (2003-2013). We compared older-aged adults with middle-aged adults on demographic, toxicological and psychiatric variables and modelled independent predictors of referral for psychiatric hospitalisation on discharge with logistic regression. RESULTS: There were (n = 157) older-aged and (n = 925) middle-aged adults. The older-aged group was similar to the middle-aged group in several ways: proportion living alone, reporting suicidal ideation/planning, prescribed antidepressant and antipsychotic drugs, and with a psychiatric diagnosis. However, the older-aged group were also different in several ways: greater proportion with cognitive impairment, higher medical morbidity, longer length of stay, and greater prescription and ingestion of benzodiazepines in the deliberate self-poisoning event. Older age was not a predictor of referral for psychiatric hospitalisation in the multivariate model. CONCLUSION: Older-aged patients treated for deliberate self-poisoning have a range of clinical needs including ones that are both similar to and different from middle-aged patients. Individual clinical assessment to identify these needs should be followed by targeted interventions, including reduced exposure to benzodiazepines.

Is the reported increase in young female hospital-treated intentional self-harm real or artefactual?

BACKGROUND: The Australian Institute of Health and Welfare has reported an increased rate of hospital-treated intentional self-harm in young females (2000-2012) in Australia. These reported increases arise from institutional data that are acknowledged to underestimate the true rate, although the degree of underestimation is not known. OBJECTIVE: To consider whether the reported increase in young females' hospital-treated intentional self-harm is real or artefactual and specify the degree of institutional underestimation. METHODS: Averages for age- and gender-standardised event rates for hospital-treated intentional self-harm (national: Australian Institute of Health and Welfare; state: New South Wales Ministry of Health) were compared with sentinel hospital event rates for intentional self-poisoning (Hunter Area Toxicology Service, Calvary Mater Newcastle) in young people (15-24 years) for the period 2000-2012. A time series analysis of the event rates for the sentinel hospital was conducted. RESULTS: The sentinel hospital event rates for young females of 444 per 100,000 were higher than the state (378 per 100,000) and national (331 per 100,000) rates. There was little difference in young male event rates - sentinel unit: 166; state: 166 and national: 153 per 100,000. The sentinel hospital rates showed no change over time for either gender. CONCLUSION: There was no indication from the sentinel unit data of any increase in rates of intentional self-poisoning for young females. The sentinel and state rates were higher than the national rates, demonstrating the possible magnitude of underestimation of the national data. The reported increases in national rates of hospital-treated self-harm among young females might be due to artefactual factors, such as changes in clinical practice (greater proportion admitted), improved administrative coding of suicidal behaviours or possibly increased hospital presentations of community self-injury cases, but not intentional self-poisoning. A national system of sentinel units is needed for the accurate and timely monitoring of all hospital-treated self-harm.

The inhalation effects of by-products from chlorination of heated indoor swimming pools on spinal development in pup mice.

INTRODUCTION: It has been postulated that swimming in heated indoor swimming pools in the first year of life is associated with the development of spinal deformity in children. We explored in pup mice whether exposure to certain disinfection by-products resulting from chlorination of heated pools would affect the future development of the spinal column. METHODS: Mice, from birth and for 28 consecutive days, were exposed to chemicals known to be created by disinfection by-products of indoor heated swimming pools. The study made use of a body fluid analogue and a chlorine source to recreate the conditions found in municipal pools. A cohort of 51 wild-type C57B6 mice, male and female, were divided into two groups: experimental (n = 29) and controls (n = 22). 24 mice were observed for 8 months (32 weeks), with 27 culled at 4 months (16 weeks). Serial CT scanning was used to assess the spines. RESULTS: Exposure to disinfection by-products resulted in an increase in the normal thoracic kyphotic spinal angle of the mice when compared with their controls at 10 weeks; experimental mice kyphosis range 35-82° versus 29-38° in controls. At 14 weeks the kyphosis of the experimental mice had reduced in size but never to that of the control group. CONCLUSION: We have demonstrated the ability to influence spinal development in pup mice through environmental factors and shown that the developmental deformity became evident only after a significant latent period.

Predicting suicidal behaviours using clinical instruments: systematic review and meta-analysis of positive predictive values for risk scales.

BackgroundPrediction of suicidal behaviour is an aspirational goal for clinicians and policy makers; with patients classified as 'high risk' to be preferentially allocated treatment. Clinical usefulness requires an adequate positive predictive value (PPV).AimsTo identify studies of predictive instruments and to calculate PPV estimates for suicidal behaviours.MethodA systematic review identified studies of predictive instruments. A series of meta-analyses produced pooled estimates of PPV for suicidal behaviours.ResultsFor all scales combined, the pooled PPVs were: suicide 5.5% (95% CI 3.9-7.9%), self-harm 26.3% (95% CI 21.8-31.3%) and self-harm plus suicide 35.9% (95% CI 25.8-47.4%). Subanalyses on self-harm found pooled PPVs of 16.1% (95% CI 11.3-22.3%) for high-quality studies, 32.5% (95% CI 26.1-39.6%) for hospital-treated self-harm and 26.8% (95% CI 19.5-35.6%) for psychiatric in-patients.ConclusionsNo 'high-risk' classification was clinically useful. Prevalence imposes a ceiling on PPV. Treatment should reduce exposure to modifiable risk factors and offer effective interventions for selected subpopulations and unselected clinical populations.

Impact of Stoma Baseplate Convexity on Tension and Compression Around the Stoma Site: A Finite Element Analysis.

For patients living with intestinal or urinary stomas, skin barriers play an essential role in protecting the peristomal skin and preventing peristomal complications. Convex baseplates press into the peristomal skin and are suitable for retracted stomas that do not protrude, peristomal skin with creases, folds, or dips, and stomas where frequent leaking can occur with flat pouching systems. However, there is a lack of data on the magnitude and location of tension applied to the abdomen by convex baseplates. We evaluated the impact of a range of convex baseplates applied to a simulated stoma site. A comparative finite element analysis investigation was conducted to evaluate the impact of eight different convex stoma system baseplates applied to an idealised flat abdomen, representing skin, subcutaneous tissue, and musculature layers. The baseplates considered had varying convexity with depths of 3.5 mm and 7 mm and internal structural diameters between ~30 mm and ~60 mm. The convex product range provided tension in the skin (maximum principal strain) and compression through the fat layer (minimum principal strain). Large differences in the locations and magnitudes of skin tension and fat layer compression were seen between the baseplates under analysis, with both the depth and diameter of convexity influencing the strain experienced across the abdominal topography. The results generated highlight the importance of having an appropriate range of convexity products available and selecting an appropriate option for use based on the stoma type and condition of the peristomal skin.

Global prevalence of psychosocial assessment following hospital-treated self-harm: systematic review and meta-analysis.

BACKGROUND: Hospital-treated self-harm is common, costly and associated with repeated self-harm and suicide. Providing a comprehensive psychosocial assessment following self-harm is recommended by professional bodies and may improve outcomes. AIMS: To review the provision of psychosocial assessments after hospital-presenting self-harm and the extent to which macro-level factors indicative of service provision explain variability in these estimates. METHOD: We searched five electronic databases to 3 January 2023 for studies reporting data on the proportion of patients and/or events that were provided a psychosocial assessment. Pooled weighted prevalence estimates were calculated with the random-effects model. Random-effects meta-regression was used to investigate between-study variability. RESULTS: 119 publications (69 unique samples) were included. Across ages, two-thirds of patients had a psychosocial assessment (0.67, 95% CI 0.58-0.76). The proportion was higher for young people and older adults (0.75, 95% CI 0.36-0.99 and 0.83, 95% CI 0.48-1.00, respectively) compared with adults (0.64, 95% CI 0.54-0.73). For events, around half of all presentations had these assessments across the age range. No macro-level factor explained between-study heterogeneity. CONCLUSIONS: There is room for improvement in the universal provision of psychosocial assessments for self-harm. This represents a missed opportunity to review and tailor aftercare supports for those at risk. Given the marked unexplained heterogeneity between studies, the person- and system-level factors that influence provision of psychosocial assessments after self-harm should be studied further.

Global prevalence of psychiatric in- and out-patient treatment following hospital-presenting self-harm: a systematic review and meta-analysis.

Background: Hospital-treated self-harm is common, costly, and strongly associated with suicide. Whilst effective psychosocial interventions exist, little is known about what key factors might modify the clinical decision to refer an individual to psychiatric in- and/or out-patient treatment following an episode of hospital-treated self-harm. Methods: We searched five electronic databases (CENTRAL, CDSR, MEDLINE, Embase, and PsycINFO) until 3 January 2023 for studies reporting data on either the proportion of patients and/or events that receive a referral and/or discharge to psychiatric in- and/or outpatient treatment after an episode of hospital-treated self-harm. Pooled weighted prevalence estimates were calculated using the random effects model with the Freedman-Tukey double arcsine adjustment in R, version 4.0.5. We also investigated whether several study-level and macro-level factors explained variability for these outcomes using random-effects meta-regression. The protocol of this review was pre-registered with PROSPERO (CRD42021261531). Findings: 189 publications, representing 131 unique studies, which reported data on 243,953 individual participants who had engaged in a total of 174,359 episodes of self-harm were included. Samples were drawn from 44 different countries. According to World Bank classifications, most (83.7%) samples were from high income countries. Across the age range, one-quarter of persons were referred for inpatient psychiatric care and, of these, around one-fifth received treatment. Just over one-third were referred to outpatient psychiatric care, whilst around half of those referred received at least one treatment session across the age range. Event rate estimates were generally of a lower magnitude. Subgroup analyses found that older adults (mean sample age: ≥60 years) may be less likely than young people (mean sample age: ≤25 years) and adults (mean sample age: >25 years to <60 years) to be referred for outpatient psychiatric care following self-harm. More recent studies were associated with a small increase in the proportion of presentations (events) that were referred to, and received, psychiatric outpatient treatment. No macro-level factor explained between-study heterogeneity. Interpretation: There is considerable scope for improvement in the allocation and provision of both in- and out-patient psychiatric care following hospital-presenting self-harm, particularly considering that the period after discharge from general hospitals represents the peak risk period for repeat self-harm and suicide. Given the marked between-study heterogeneity, the basis for allocation of aftercare treatment is therefore not yet known and should be further studied. Funding: There was no specific funding for this review.

Prevalence of Depression and Predictors of Discharge to a Psychiatric Hospital in Young People with Hospital-Treated Deliberate Self-Poisoning at an Australian Sentinel Unit.

OBJECTIVE: Hospital treated deliberate self-poisoning is common in young people. Internationally, estimates of rates of depression in this population are very wide (14.6% to 88%). The aims of this study were to determine the prevalence of depression and the independent predictors of referral for psychiatric hospitalisation in young people (aged 16 to 25 years) following an index episode of hospital treated deliberate self-poisoning. METHOD: A retrospective cohort study design (n = 1410), with data drawn from a population-based clinical case register. Unadjusted and adjusted estimates of predictors of referral for psychiatric admission (after-care) used logistic regression models. RESULTS: Prevalence of any depression diagnosis was 35.5% (n = 500); and 25.4% (n = 358) were referred for a psychiatric admission. The adjusted estimates for predictors of psychiatric inpatient referral were: high suicidal level (OR 118.21: CI 95% 63.23-220.99), low/moderate suicidal level (14.27: 9.38-21.72), any depression (2.88: 1.97-4.22), any psychosis (4.06; 1.15-14.36), older age (1.12: 1.04-1.21), and number of support people (0.88: 0.78-0.98). CONCLUSION: Depression was diagnosed in more than a third and was an independent predictor of psychiatric inpatient referral, so service providers need to account for this level of need in the provision of assessment and after-care services. Evidence-based guidelines for psychiatric inpatient after-care for deliberate self-poisoning and/or depression in young people are limited. Our explanatory model included suicidal level, depression, psychosis, older age, and available support persons, suggesting that the treating clinicians were making these discharge decisions for admission in keeping with those limited guidelines, although the balance of benefits and harms of psychiatric hospitalisation are not established. Future research examining patient experiences, effectiveness of psychiatric hospitalisation, and alternatives to hospitalisation is warranted.

Effectiveness of the Hunter Way Back Support Service: An historical controlled trial of a brief non-clinical after-care program for hospital-treated deliberate self-poisoning.

INTRODUCTION: Active contact and follow-up interventions have been shown to be effective in reducing repetition of hospital-treated self-harm. The Way Back Support Service (WBSS) is a new service funded by the Australian government to provide three months of non-clinical after-care following a hospital-treated suicide attempt. The aim of this study was to investigate the effectiveness of WBSS in reducing deliberate self-poisoning (DSP) and psychiatric hospital admissions over a 12-month follow-up period for a population of DSP patients within the Hunter (Australia) region. METHODS: A non-randomized, historical controlled (two periods) trial design with intention-to-treat analyses. Outcome data were drawn from hospital records. RESULTS: There were a total of 2770 participants across study periods. There were no significant differences between cohorts for proportion with any, or number of, re-admissions for DSP in the follow-up period. For psychiatric admissions, the intervention cohort had a non-significantly greater proportion with any psychiatric admission and significantly more admissions compared to one of the control cohorts. CONCLUSION: The WBSS model of care should be modified to strengthen treatment engagement and retention and to include established, clinical, evidence-based treatments shown to reduce DSP repetition. Any modified WBSS model should be subject to further evaluation.

Indigeneity and Likelihood of Discharge to Psychiatric Hospital in an Australian Deliberate Self-Poisoning Hospital-Treated Cohort.

Hospital-treated self-harm rates for Aboriginal and Torres Strait Islander (Indigenous) people are at least double those for other Australians. Despite this, limited research has explored the relationship between Indigeneity and the clinical management of hospital-treated deliberate self-harm. A retrospective clinical cohort study (2003-2012) at a regional referral centre (NSW) for deliberate self-poisoning was used to explore the magnitude and direction of the relationship between Indigeneity and discharge destination (psychiatric hospital vs. other) using a series of logistic regressions. There were 149 (4%) Indigenous and 3697 (96%) non-Indigenous deliberate self-poisoning admissions during the study period. One-third (31%) were referred to the psychiatric hospital at discharge; Indigenous 21% (n = 32) vs. non-Indigenous 32% (n = 1175). Those who identified as Indigenous were less likely to be discharged to the psychiatric hospital, OR 0.59 (0.40-0.87) at the univariate level, with little change after sequential adjustment; and AOR 0.34 (0.21-0.73) in the fully adjusted model. The Indigenous cohort had a lower likelihood of psychiatric hospital discharge even after adjustment for variables associated with discharge to the psychiatric hospital highlighting the need for further investigation of the reasons accounting for this differential pattern of clinical management and the effectiveness of differential after-care allocation.

Developing a tailored implementation action plan for a suicide prevention clinical intervention in an Australian mental health service: A qualitative study using the EPIS framework.

Background: Tailoring implementation strategies to local contexts is a promising approach to supporting implementation and sustainment of evidence-based practices in health settings. While there is increasing research on tailored implementation of mental health interventions, implementation research on suicide prevention interventions is limited. This study aimed to evaluate implementation and subsequently develop a tailored action plan to support sustainment of an evidence-based suicide prevention intervention; Collaborative Assessment and Management of Suicidality (CAMS) in an Australian public mental health service. Methods: Approximately 150 mental health staff working within a regional and remote Local Health District in Australia were trained in CAMS. Semi-structured interviews and focus groups with frontline staff and clinical leaders were conducted to examine barriers and facilitators to using CAMS. Data were analysed using a reflexive thematic analysis approach and mapped to the Exploration, Preparation, Implementation and Sustainment (EPIS) framework and followed by stakeholder engagement to design a tailored implementation action plan based on a 'tailored blueprint' methodology. Results: A total of 22 barriers to implementing CAMS were identified. Based on the perceived impact on implementation fidelity and the feasibility of addressing identified barriers, six barriers were prioritised for addressing through an implementation action plan. These barriers were mapped to evidence-based implementation strategies and, in collaboration with local health district staff, goals and actionable steps for each strategy were generated. This information was combined into a tailored implementation plan to support the sustainable use of CAMS as part of routine care within this mental health service. Conclusions: This study provides an example of a collaborative approach to tailoring strategies for implementation on a large scale. Novel insights were obtained into the challenges of evaluating the implementation process and barriers to implementing an evidence-based suicide prevention treatment approach within a geographically large and varied mental health service in Australia. Plain language abstract: This study outlines the process of using a collaborative stakeholder engagement approach to develop tailored implementation plans. Using the Exploration Preparation Implementation Sustainment Framework, findings identify the barriers to and strategies for implementing a clinical suicide prevention intervention in an Australian community mental health setting. This is the first known study to use an implementation science framework to investigate the implementation of the clinical suicide prevention intervention (Collaborative Assessment and Management of Suicidality) within a community mental health setting. This work highlights the challenges of conducting implementation research in a dynamic public health service.

Information needs of people after a suicide attempt: A thematic analysis.

OBJECTIVE: This study aimed to identify the information that people who have attempted suicide and those who support them believed to be helpful to receive after an attempt. METHODS: Thirty-seven people with lived experience of suicide attempt(s) (suicide attempt survivors and family members/friends of survivors) were recruited through two national lived experience community groups in Australia. Participants completed a semi-structured telephone interview that included questions about the types of information they believed important to receive after an attempt. RESULTS: Using thematic analysis, the key information participants identified was helpful to receive following a suicide attempt was that which could challenge stigma and address negative community attitudes towards suicide. Participants spoke of a need for practical information and information that provided hope. Personal stories of recovery were identified as an important way of communicating this sort of health information. CONCLUSIONS: People who have attempted suicide and their family members and friends want information that challenges stigma and supports recovery expectations. PRACTICE IMPLICATIONS: Providing people with accurate information about recovery and using personal stories to communicate health information is one way people affected by suicide attempt identify can challenge stigma, and address information needs after a suicide attempt.

A Targeted Mutation Disrupting Mitochondrial Complex IV Function in Primary Afferent Neurons Leads to Pain Hypersensitivity Through P2Y1 Receptor Activation.

As mitochondrial dysfunction is evident in neurodegenerative disorders that are accompanied by pain, we generated inducible mutant mice with disruption of mitochondrial respiratory chain complex IV, by COX10 deletion limited to sensory afferent neurons through the use of an Advillin Cre-reporter. COX10 deletion results in a selective energy-deficiency phenotype with minimal production of reactive oxygen species. Mutant mice showed reduced activity of mitochondrial respiratory chain complex IV in many sensory neurons, increased ADP/ATP ratios in dorsal root ganglia and dorsal spinal cord synaptoneurosomes, as well as impaired mitochondrial membrane potential, in these synaptoneurosome preparations. These changes were accompanied by marked pain hypersensitivity in mechanical and thermal (hot and cold) tests without altered motor function. To address the underlying basis, we measured Ca2+ fluorescence responses of dorsal spinal cord synaptoneurosomes to activation of the GluK1 (kainate) receptor, which we showed to be widely expressed in small but not large nociceptive afferents, and is minimally expressed elsewhere in the spinal cord. Synaptoneurosomes from mutant mice showed greatly increased responses to GluK1 agonist. To explore whether altered nucleotide levels may play a part in this hypersensitivity, we pharmacologically interrogated potential roles of AMP-kinase and ADP-sensitive purinergic receptors. The ADP-sensitive P2Y1 receptor was clearly implicated. Its expression in small nociceptive afferents was increased in mutants, whose in vivo pain hypersensitivity, in mechanical, thermal and cold tests, was reversed by a selective P2Y1 antagonist. Energy depletion and ADP elevation in sensory afferents, due to mitochondrial respiratory chain complex IV deficiency, appear sufficient to induce pain hypersensitivity, by ADP activation of P2Y1 receptors.

Accuracy of Clinician Predictions of Future Self-Harm: A Systematic Review and Meta-Analysis of Predictive Studies.

Assessment of a patient after hospital-treated self-harm or psychiatric hospitalization often includes a risk assessment, resulting in a classification of high risk versus low risk for a future episode of self-harm. Through systematic review and a series of meta-analyses looking at unassisted clinician risk classification (eight studies; N = 22,499), we found pooled estimates for sensitivity 0.31 (95% CI: 0.18-0.50), specificity 0.85 (0.75-0.92), positive predictive value 0.22 (0.21-0.23), and negative predictive value 0.89 (0.86-0.92). Clinician classification was too inaccurate to be clinically useful. After-care should therefore be allocated on the basis of a needs rather than risk assessment.