Variation in the clinical management of self-harm by area-level socio-economic deprivation: findings from the multicenter study of self-harm in England.

BACKGROUND: We investigated disparities in the clinical management of self-harm following hospital presentation with self-harm according to level of socio-economic deprivation (SED) in England. METHODS: 108 092 presentations to hospitals (by 57 306 individuals) after self-harm in the Multicenter Study of Self-harm spanning 17 years. Area-level SED was based on the English Index of Multiple Deprivation. Information about indicators of clinical care was obtained from each hospital's self-harm monitoring systems. We assessed the associations of SED with indicators of care using mixed effect models. RESULTS: Controlling for confounders, psychosocial assessment and admission to a general medical ward were less likely for presentations by patients living in more deprived areas relative to presentations by patients from the least deprived areas. Referral for outpatient mental health care was less likely for presentations by patients from the two most deprived localities (most deprived: adjusted odd ratio [aOR] 0.77, 95% CI 0.71-0.83, p < 0.0001; 2nd most deprived: aOR 0.80, 95% CI 0.74-0.87, p < 0.0001). Referral to substance use services and 'other' services increased with increased SED. Overall, referral for aftercare was less likely following presentations by patients living in the two most deprived areas (most deprived: aOR 0.85, 95% CI 0.78-0.92, p < 0.0001; 2nd most deprived: aOR 0.86, 95% CI 0.79-0.94, p = 0.001). CONCLUSIONS: SED is associated with differential care for patients who self-harm in England. Inequalities in care may exacerbate the risk of adverse outcomes in this disadvantaged population. Further work is needed to understand the reasons for these differences and ways of providing more equitable care.

Online harms? Suicide-related online experience: a UK-wide case series study of young people who die by suicide.

BACKGROUND: Few studies have examined online experience by young people who die by suicide. METHODS: A 3-year UK-wide consecutive case series of all young people aged 10-19 who died by suicide, based on national mortality data. We extracted information on the antecedents of suicide of 544 of these 595 deaths (91%) from official investigations, mainly inquests. RESULTS: Suicide-related online experience was reported in 24% (n = 128/544) of suicide deaths in young people between 2014 and 2016, equivalent to 43 deaths per year, and was more common in girls than boys (OR 1.87, 95% CI 1.23-2.85, p = 0.003) and those identifying as LGBT (OR 2.35, 95% CI 1.10-5.05, p = 0.028). Searching for information about method was most common (n = 68, 13%), followed by posting suicidal ideas online (n = 57, 10%). Self-harm, bereavement (especially by suicide), social isolation, and mental and physical ill-health were more likely in those known to have suicide-related online experience compared to those who did not. 29 (5%) were bullied online, more often girls (OR 2.84, 1.34-6.04, p = 0.007). Online bullying often accompanied face-to-face bullying (n = 16/29, 67%). CONCLUSIONS: Suicide-related online experience is a common, but likely underestimated, antecedent to suicide in young people. Although its causal role is unclear, it may influence suicidality in this population. Mental health professionals should be aware that suicide-related online experience - not limited to social media - is a potential risk for young patients, and may be linked to experiences offline. For public health, wider action is required on internet regulation and support for children and their families.

Psychiatric morbidity and suicidal behaviour in psoriasis: a primary care cohort study.

BACKGROUND: Psychological distress among people with psoriasis may lead to elevated risks of suicide and nonfatal self-harm. OBJECTIVES: To investigate psychiatric comorbidity, psychotropic medication prescribing and risk of suicidality in people with psoriasis. METHODS: A cohort of patients with psoriasis (1998-2014) was delineated using the Clinical Practice Research Datalink, with linkage to Hospital Episode Statistics and Office for National Statistics mortality records. Each patient with psoriasis was matched with up to 20 patients without psoriasis on age, sex and general practice. A stratified Cox regression model was used to estimate the hazard ratios (HRs) for suicide or nonfatal self-harm risks adjusted for socioeconomic status. RESULTS: At baseline, among 56 961 and 876 919 patients with and without psoriasis, higher prevalence for histories of alcohol misuse, bipolar disorder, depression, anxiety disorders, self-harm and psychotropic drug prescription were observed. The deprivation-adjusted HR indicated lower suicide risk in people with psoriasis [HR 0·59, 95% confidence interval (CI) 0·41-0·85]. The risk of suicide varied according to age: it was lower in people with psoriasis diagnosed at ≥ 40 years (HR 0·38, 95% CI 0·21-0·66), whereas there was no difference in risk of suicide in people with psoriasis diagnosed before age 40 years (HR 0·92, 95% CI 0·58-1·46). Conversely, there was a small increased risk for self-harm (HR 1·15, 95% CI 1·04-1·27) associated with psoriasis. CONCLUSIONS: The prevalence of mental illness was raised in people with psoriasis, and this may lead to a greater risk of self-harm. Nevertheless, having psoriasis does not appear to be associated with an increased risk of suicide. Healthcare professionals caring for patients with psoriasis should continue to monitor and tackle effectively the psychological needs of these individuals.

Meta-analysis of suicide rates among people discharged from non-psychiatric settings after presentation with suicidal thoughts or behaviours.

OBJECTIVE: To quantify the suicide rate among people discharged from non-psychiatric settings after presentations with suicidal thoughts or behaviours. METHOD: Meta-analysis of studies reporting suicide deaths among people with suicidal thoughts or behaviours after discharge from emergency departments or the medical or surgical wards of general hospitals. RESULTS: A total of 115 studies reported 167 cohorts and 3747 suicide deaths among 248 005 patients during 1 263 727 person-years. The pooled suicide rate postdischarge was 483 suicide deaths per 100 000 person-years (95% confidence interval (CI) 445-520, prediction interval (PI) 200-770) with high between-sample heterogeneity (I2  = 92). The suicide rate was highest in the first year postdischarge (851 per 100 000 person-years) but remained elevated in the long term. Suicide rates were elevated among samples of men (716 per 100 000 person-years) and older people (799 per 100 000 person-years) but were lower in samples of younger people (107 per 100 000 person-years) and among studies published between 2010 and 2018 (329 per 100 000 person-years). CONCLUSIONS: People with suicidal thoughts or behaviours who are discharged from non-psychiatric settings have highly elevated rates of suicide despite a clinically meaningful decline in these suicide rates in recent decades.

Psychosocial, psychiatric and work-related risk factors associated with suicide in Ireland: optimised methodological approach of a case-control psychological autopsy study.

BACKGROUND: Suicide has profound effects on families and communities, but is a statistically rare event. Psychological autopsies using a case-control design allow researchers to examine risk factors for suicide, using a variety of sources to detail the psychological and social characteristics of decedents and to compare them to controls. The Suicide Support and Information System Case Control study (SSIS-ACE) aimed to compare psychosocial, psychiatric and work-related risk factors across three groups of subjects: suicide decedents, patients presenting to hospital with a high-risk self-harm episode, and general practice controls. METHODS: The study design includes two inter-related studies; one main case-control study: comparing suicide cases to general practice (GP) controls, and one comparative study: comparing suicide cases to patients presenting with high-risk self-harm. Consecutive cases of suicide and probable suicide are identified through coroners' registration of deaths in the defined region (Cork City and County, Ireland) and are frequency-matched for age group and gender with GP patient controls recruited from the same GP practice as the deceased. Data sources for suicide cases include coroners' records, interviews with health care professionals and proxy informants; data sources for GP controls and for high-risk self-harm controls include interviews with control, with proxy informants and with health care professionals. Interviews are semi-structured and consist of quantitative and qualitative parts. The quantitative parts include a range of validated questionnaires addressing psychiatric, psychosocial and occupational factors. The study adopts several methodological innovations, including accessing multiple data sources for suicide cases and controls simultaneously, recruiting proxy informants to examine consistency across sources. CONCLUSIONS: The study allows for the investigation of consistency across different data sources and contributes to the methodological advancement of psychological autopsy research. The study will also inform clinical and public health practice. The comparison between suicide cases and controls will allow investigation of risk and protective factors for suicide more generally, while the comparison with high-risk self-harm patients will help to identify the factors associated specifically with a fatal outcome to a self-harm episode. A further enhancement is the particular focus on specific work-related risk factors for suicide.

Routine hospital management of self-harm and risk of further self-harm: propensity score analysis using record-based cohort data.

BACKGROUND: The care received by people presenting to hospital following self-harm varies and it is unclear how different types of treatment affect risk of further self-harm. METHOD: Observational cohort data from the Manchester Self-Harm Project, UK, included 16 456 individuals presenting to an Emergency Department with self-harm between 2003 and 2011. Individuals were followed up for 12 months. We also used data from a smaller cohort of individuals presenting to 31 hospitals in England during a 3-month period in 2010/2011, followed up for 6 months. Propensity score (PS) methods were used to address observed confounding. Missing data were imputed using multiple imputation. RESULTS: Following PS stratification, those who received a psychosocial assessment had a lower risk of repeat hospital attendance for self-harm than those who were not assessed [RR 0.87, 95% confidence interval (CI) 0.80-0.95]. The risk was reduced most among people less likely to be assessed. Following PS matching, we found no associations between risks of repeat self-harm and admission to a medical bed, referral to outpatient psychiatry or admission to a psychiatric bed. We did not find a relationship between psychosocial assessment and repeat self-harm in the 31 centre cohort. CONCLUSIONS: This study shows the potential value of using novel statistical techniques in large mental health datasets to estimate treatment effects. We found that specialist psychosocial assessment may reduce the risk of repeat self-harm. This type of routine care should be provided for all individuals who present to hospital after self-harm, regardless of perceived risk.

Interventions to reduce the impact of unemployment and economic hardship on mental health in the general population: a systematic review.

BACKGROUND: Job loss, debt and financial difficulties are associated with increased risk of mental illness and suicide in the general population. Interventions targeting people in debt or unemployed might help reduce these effects. METHOD: We searched MEDLINE, Embase, The Cochrane Library, Web of Science, and PsycINFO (January 2016) for randomized controlled trials (RCTs) of interventions to reduce the effects of unemployment and debt on mental health in general population samples. We assessed papers for inclusion, extracted data and assessed risk of bias. RESULTS: Eleven RCTs (n = 5303 participants) met the inclusion criteria. All recruited participants were unemployed. Five RCTs assessed 'job-club' interventions, two cognitive behaviour therapy (CBT) and a single RCT assessed each of emotional competency training, expressive writing, guided imagery and debt advice. All studies were at high risk of bias. 'Job club' interventions led to improvements in levels of depression up to 2 years post-intervention; effects were strongest among those at increased risk of depression (improvements of up to 0.2-0.3 s.d. in depression scores). There was mixed evidence for effectiveness of group CBT on symptoms of depression. An RCT of debt advice found no effect but had poor uptake. Single trials of three other interventions showed no evidence of benefit. CONCLUSIONS: 'Job-club' interventions may be effective in reducing depressive symptoms in unemployed people, particularly those at high risk of depression. Evidence for CBT-type interventions is mixed; further trials are needed. However the studies are old and at high risk of bias. Future intervention studies should follow CONSORT guidelines and address issues of poor uptake.

Suicide by mental health in-patients under observation.

BACKGROUND: Observations in psychiatric in-patient settings are used to reduce suicide, self-harm, violence and absconding risk. The study aims were to describe the characteristics of in-patients who died by suicide under observation and examine their service-related antecedents. METHOD: A national consecutive case series in England and Wales (2006-2012) was examined. RESULTS: There were 113 suicides by in-patients under observation, an average of 16 per year. Most were under intermittent observation. Five deaths occurred while patients were under constant observation. Patient deaths were linked with the use of less experienced staff or staff unfamiliar with the patient, deviation from procedures and absconding. CONCLUSIONS: We identified key elements of observation that could improve safety, including only using experienced and skilled staff for the intervention and using observation levels determined by clinical need not resources.

Seeking help in times of economic hardship: access, experiences of services and unmet need.

BACKGROUND: Economic recessions are often accompanied by increased levels of psychological distress and suicidal behaviour in affected populations. Little is known about the experiences of people seeking help for employment, financial and benefit-related difficulties during recessions. We investigated the experiences of people struggling financially in the aftermath of the Great Recession (2008-9) - including some who had self-harmed - and of the frontline support staff providing assistance. METHODS: Interviews were conducted with three groups of people in two cities: i) people who had self-harmed due to employment, financial or benefit concerns (n = 19) ('self-harm'); ii) people who were struggling financially drawn from the community (n = 22), including one focus group) ('community'); iii) and frontline staff from voluntary and statutory sector organisations (e.g., Job Centres, Debt Advice and counselling agencies) providing support services to the groups (n = 25, including 2 focus groups) ('service providers'). Data were analysed using the constant comparison method. RESULTS: Service provision was described by people as confusing and difficult to access. The community sample reported considerably more knowledge and access to debt advice than the participants who had self-harmed - although both groups sought similar types of help. The self-harm group exhibited greater expectation that they should be self-reliant and also reported lower levels of informal networks and support from friends and relatives. They had also experienced more difficult circumstances such as benefit sanctions, and most had pre-existing mental health problems. Both self-harm and community groups indicated that practical help for debt and benefit issues would be the most useful - a view supported by service providers - and would have particularly helped those who self-harmed. CONCLUSION: Interventions to identify those in need and aid them to access practical, reliable and free advice from support agencies could help mitigate the impact on mental health of benefit, debt and employment difficulties for vulnerable sections of society.

Suicide risk linked with clinical consultation frequency, psychiatric diagnoses and psychotropic medication prescribing in a national study of primary-care patients.

BACKGROUND: Little is known about the precursors of suicide risk among primary-care patients. This study aimed to examine suicide risk in relation to patterns of clinical consultation, psychotropic drug prescribing, and psychiatric diagnoses. METHOD: Nested case-control study in the Clinical Practice Research Datalink (CPRD), England. Patients aged ⩾16 years who died by suicide during 2002-2011 (N = 2384) were matched on gender, age and practice with up to 20 living control patients (N = 46 899). RESULTS: Risk was raised among non-consulting patients, and increased sharply with rising number of consultations in the preceding year [⩾12 consultations v. 1: unadjusted odds ratio (OR) 6.0, 95% confidence interval (CI) 4.9-7.3]. Markedly elevated risk was also associated with the prescribing of multiple psychotropic medication types (⩾5 types v. 0: OR 62.6, CI 44.3-88.4) and with having several psychiatric diagnoses (⩾4 diagnoses v. 0: OR 31.1, CI 19.3-50.1). Risk was also raised among patients living in more socially deprived localities. The confounding effect of multiple psychotropic drug types largely accounted for the rising risk gradient observed with increasing consultation frequency. CONCLUSIONS: A greater proportion of patients with several psychiatric diagnoses, those prescribed multiple psychotropic medication types, and those who consult at very high frequency might be considered for referral to mental health services by their general practitioners. Non-consulters are also at increased risk, which suggests that conventional models of primary care may not be effective in meeting the needs of all people in the community experiencing major psychosocial difficulties.

Suicide in patients suffering from late-life anxiety disorders; a comparison with younger patients.

BACKGROUND: Anxiety disorders are assumed to increase suicide risk, although confounding by comorbid psychiatric disorders may be one explanation. This study describes the characteristics of older patients with an anxiety disorder who died by suicide in comparison to younger patients. METHOD: A 15-year national clinical survey of all suicides in the UK (n = 25,128). Among the 4,481 older patients who died by suicide (≥ 60 years), 209 (4.7%) suffered from a primary anxiety disorder, and 533 (11.9%) from a comorbid anxiety disorder. Characteristics of older (n = 209) and younger (n = 773) patients with a primary anxiety disorder were compared by logistic regression adjusted for sex and living arrangement. RESULTS: Compared to younger patients, older patients with a primary anxiety disorder were more often males and more often lived alone. Although 60% of older patients had a history of psychiatric admissions and 50% of deliberate self-harm, a history of self-harm, violence, and substance misuse was significantly less frequent compared to younger patients, whereas physical health problems and comorbid depressive illness were more common. Older patients were prescribed significantly more psychotropic drugs and received less psychotherapy compared to younger patients. CONCLUSION: Anxiety disorders are involved in one of every six older patients who died by suicide. Characteristics among patients who died by suicide show severe psychopathology, with a more prominent role for physical decline and social isolation compared to their younger counterparts. Moreover, treatment was less optimal in the elderly, suggesting ageism. These results shed light on the phenomenon of suicide in late-life anxiety disorder and suggest areas where prevention efforts might be focused.

Propranolol: a novel treatment for angiolymphoid hyperplasia with eosinophilia.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon, idiopathic disease that manifests as dermal or subcutaneous red or brown papules or nodules, most commonly on the head and neck. Histologically, ALHE is characterized by vascular proliferation with epithelioid endothelial cells with surrounding lymphocytic and eosinophilic infiltrate. There may be an accompanying serum eosinophilia and local lymphadenopathy. We report a case of a 32-year-old woman who presented with multiple erythematous nodules in the periauricular area and the vertex of her scalp. The nodules had been present for several months. Surgical removal of one of the lesions confirmed the histological diagnosis of ALHE. The patient was started on oral propranolol (40 mg once daily) in an effort to reduce the vascular component of the lesions. Within 6 weeks, the patient noted that several of the lesions had decreased in size, and all were less erythematous. Propranolol was subsequently stopped within a few months of initiating treatment. One lesion recurred over a year later, and propranolol was then restarted. No new lesions occurred after 2 years of follow-up.

Flow-Xl: a new facility for the analysis of crystallization in flow systems.

Characterization of crystallization processes in situ is of great importance to furthering knowledge of how nucleation and growth processes direct the assembly of organic and inorganic materials in solution and, critically, understanding the influence that these processes have on the final physico-chemical properties of the resulting solid form. With careful specification and design, as demonstrated here, it is now possible to bring combined X-ray diffraction and Raman spectroscopy, coupled to a range of fully integrated segmented and continuous flow platforms, to the laboratory environment for in situ data acquisition for timescales of the order of seconds. The facility used here (Flow-Xl) houses a diffractometer with a micro-focus Cu Kα rotating anode X-ray source and a 2D hybrid photon-counting detector, together with a Raman spectrometer with 532 and 785 nm lasers. An overview of the diffractometer and spectrometer setup is given, and current sample environments for flow crystallization are described. Commissioning experiments highlight the sensitivity of the two instruments for time-resolved in situ data collection of samples in flow. Finally, an example case study to monitor the batch crystallization of sodium sulfate from aqueous solution, by tracking both the solute and solution phase species as a function of time, highlights the applicability of such measurements in determining the kinetics associated with crystallization processes. This work illustrates that the Flow-Xl facility provides high-resolution time-resolved in situ structural phase information through diffraction data together with molecular-scale solution data through spectroscopy, which allows crystallization mechanisms and their associated kinetics to be analysed in a laboratory setting.

Hospitalization for physical illness and risk of subsequent suicide: a population study.

OBJECTIVE: To examine suicide risk in relation to physical illness across a broad range of illnesses, including hospitalization history, specific organ or system illness and comorbidity. DESIGN: A nested case-control study. SETTING: Data were retrieved from five Danish national registers. SUBJECTS: On the basis of the entire population of Denmark, this study included 27 262 suicide cases, and 468 007 live controls matched for sex and date of birth. MAIN OUTCOME MEASURES: Risk of suicide was assessed using conditional logistic regression. RESULTS: In the study population, 63.5% of suicide cases and 44.5% of comparison controls had a history of hospitalization for physical illness. A physical illness significantly increased the risk of subsequent suicide (incidence rate ratios 2.13, 95% CI 2.07-2.18) with a substantially greater effect in women than in men (P < 0.01). The elevated risk increased progressively with frequency and recency of hospitalization and was significant for diseases occurring in all organs or systems of the body. Comorbidity involving several organs or systems increased the risk substantially. The associated estimates were to some extent reduced but remained highly significant after adjustment for psychiatric history and socio-economic status. Taking into account both prevalence and adjusted effect size, physical illness accounted for 24.4%, 21.0% and 32.3% of population attributable risk for suicide in total, male and female populations, respectively. CONCLUSIONS: Physical illness constitutes a significant risk factor for suicide independent of psychiatric and socio-economic factors. Clinicians treating physically ill patients should be aware of the risk, especially amongst those with multiple or recent hospitalizations, or multiple comorbidities.

Suicide in bipolar disorder in a national English sample, 1996-2009: frequency, trends and characteristics.

BACKGROUND: Bipolar disorder (BD) has been reported to be associated with high risk of suicide. We aimed to investigate the frequency and characteristics of suicide in people with BD in a national sample. METHOD: Suicide in BD in England from 1996 to 2009 was explored using descriptive statistics on data collected by the National Confidential Inquiry into Suicide and Homicide by People with Mental Illness (NCI). Suicide cases with a primary diagnosis of BD were compared to suicide cases with any other primary diagnosis. RESULTS: During the study period 1489 individuals with BD died by suicide, an average of 116 cases/year. Compared to other primary diagnosis suicides, those with BD were more likely to be female, more than 5 years post-diagnosis, current/recent in-patients, to have more than five in-patient admissions, and to have depressive symptoms. In BD suicides the most common co-morbid diagnoses were personality disorder and alcohol dependence. Approximately 40% were not prescribed mood stabilizers at the time of death. More than 60% of BD suicides were in contact with services the week prior to suicide but were assessed as low risk. CONCLUSIONS: Given the high rate of suicide in BD and the low estimates of risk, it is important that health professionals can accurately identify patients most likely to experience poor outcomes. Factors such as alcohol dependence/misuse, personality disorder, depressive illness and current/recent in-patient admission could characterize a high-risk group. Future studies need to operationalize clinically useful indicators of suicide risk in BD.

Psychiatric in-patient care and suicide in England, 1997 to 2008: a longitudinal study.

BACKGROUND: Psychiatric in-patients are at high risk of suicide. Recent reductions in bed numbers in many countries may have affected this risk but few studies have specifically investigated temporal trends. We aimed to explore trends in psychiatric in-patient suicide over time. METHOD: A prospective study of all patients admitted to National Health Service (NHS) in-patient psychiatric care in England (1997-2008). Suicide rates were determined using National Confidential Inquiry and Hospital Episode Statistics (HES) data. RESULTS: Over the study period there were 1942 psychiatric in-patient suicides. Between the first 2 years of the study (1997, 1998) and the last 2 years (2007, 2008) the rate of in-patient suicide fell by nearly one-third from 2.45 to 1.68 per 100,000 bed days. This fall in rate was observed for males and females, across ethnicities and diagnoses. It was most marked for patients aged 15-44 years. Rates also fell for the most common suicide methods, particularly suicide by hanging on the ward (a 59% reduction). Although the number of post-discharge suicides fell, the rate of post-discharge suicide may have increased by 19%. The number of suicide deaths in those under the care of crisis resolution/home treatment teams has increased in recent years to approximately 160 annually. CONCLUSIONS: The rate of suicide among psychiatric in-patients in England has fallen considerably. Possible explanations include falling general population rates, changes in the at-risk population or improved in-patient safety. However, a transfer of risk to the period after discharge or other clinical settings such as crisis resolution teams cannot be ruled out.

Time trends in coroners' use of different verdicts for possible suicides and their impact on officially reported incidence of suicide in England: 1990-2005.

BACKGROUND: Official suicide statistics for England are based on deaths given suicide verdicts and most cases given an open verdict following a coroner's inquest. Previous research indicates that some deaths given accidental verdicts are considered to be suicides by clinicians. Changes in coroners' use of different verdicts may bias suicide trend estimates. We investigated whether suicide trends may be over- or underestimated when they are based on deaths given suicide and open verdicts. Method Possible suicides assessed by 12 English coroners in 1990/91, 1998 and 2005 and assigned open, accident/misadventure or narrative verdicts were rated by three experienced suicide researchers according to the likelihood that they were suicides. Details of all suicide verdicts given by these coroners were also recorded. RESULTS: In 1990/91, 72.0% of researcher-defined suicides received a suicide verdict from the coroner, this decreased to 65.4% in 2005 (p trend < 0.01); equivalent figures for combined suicide and open verdicts were 95.4% (1990/91) and 86.7% (2005). Researcher-defined suicides with a verdict of accident/misadventure doubled over that period, from 4.6% to 9.1% (p < 0.01). Narrative verdict cases rose from zero in 1990/91 to 25 in 2005 (4.2% of researcher-defined suicides that year). In 1998 and 2005, 50.0% of the medicine poisoning deaths given accidental/misadventure verdicts were rated as suicide by the researchers. CONCLUSIONS: Between 1990/91 and 2005, the proportion of researcher-defined suicides given a suicide verdict by coroners decreased, largely due to an increased use of accident/misadventure verdicts, particularly for deaths involving poisoning. Consideration should be given to the inclusion of 'accidental' deaths by poisoning with medicines in the statistics available for monitoring suicides rates.

Absolute risks of self-harm and interpersonal violence by diagnostic category following first discharge from inpatient psychiatric care.

BACKGROUND: Persons discharged from inpatient psychiatric services are at greatly elevated risk of harming themselves or inflicting violence on others, but no studies have reported gender-specific absolute risks for these two outcomes across the spectrum of psychiatric diagnoses. We aimed to estimate absolute risks for self-harm and interpersonal violence post-discharge according to gender and diagnostic category. METHODS: Danish national registry data were utilized to investigate 62,922 discharged inpatients, born 1967-2000. An age and gender matched cohort study was conducted to examine risks for self-harm and interpersonal violence at 1 year and at 10 years post-discharge. Absolute risks were estimated as cumulative incidence percentage values. RESULTS: Patients diagnosed with substance misuse disorders were at especially elevated risk, with the absolute risks for either self-harm or interpersonal violence being 15.6% (95% CI 14.9, 16.3%) of males and 16.8% (15.6, 18.1%) of females at 1 year post-discharge, rising to 45.7% (44.5, 46.8%) and 39.0% (37.1, 40.8%), respectively, within 10 years. Diagnoses of personality disorders and early onset behavioral and emotional disorders were also associated with particularly high absolute risks, whilst risks linked with schizophrenia and related disorders, mood disorders, and anxiety/somatoform disorders, were considerably lower. CONCLUSIONS: Patients diagnosed with substance misuse disorders, personality disorders and early onset behavioral and emotional disorders are at especially high risk for internally and externally directed violence. It is crucial, however, that these already marginalized individuals are not further stigmatized. Enhanced care at discharge and during the challenging transition back to life in the community is needed.

Hepatitis E virus enters liver cells through receptor-dependent clathrin-mediated endocytosis.

We investigated the virus-host interaction for hepatitis E virus (HEV) by performing competitive binding assays using in vitro assembled virus-like particles (VLPs). We used Escherichia coli expressed native capsid protein (pORF2) and its mutants with an attached Gly((5))-Ala (linker) reporter [enhanced green fluorescent protein (EGFP)/firefly luciferase (Fluc)]. Transmission electron microscopy and nanoparticle tracking showed near uniform particles of approximately 30-35 nm in diameter for pORF2 VLPs and 60-100 nm for reporter-linked VLPs. Binding of reporter-linked full-length (1-660aa) and N-terminal truncated (Δ1-112aa) pORF2 VLPs to Huh7 cell surfaces was found to be specific with 1.92 ± 0.065 × 10(5) sites per cell. Saturation binding indicated an equilibrium dissociation constant (K(d)) of 121.1 ± 23.83 and 123.8 ± 16.15 nm for pORF2-linker-EGFP and pORF2-linker-Fluc VLPs respectively. A similar binding pattern was observed for Δ1-112aa pORF2-linker-EGFP and Δ1-112aa pORF2-linker-Fluc VLPs with K(d) values of 123.6 ± 10.60 and 135.6 ± 16.19 nm respectively. The affinity (log K(i)) of pORF2 binding on Huh7 cells in the presence of EGFP-tagged and Fluc-tagged pORF2 VLPs was found to be approximately 2.0. However, no VLP formation or binding was observed with refolded C-terminal truncated (Δ458-660aa) pORF2. We investigated HEV internalization using fluorescent VLPs (EGFP-VLPs), which showed vesicle-mediated uptake starting at 5 min post-incubation. The uptake of VLPs could be stopped by inhibitors for clathrin-dependent endocytosis, but not by caveosome inhibitors. No binding and uptake of EGFP-VLPs were observed on non-hepatic cell lines (HeLa and SiHa). These findings suggest that HEV attaches to the host cell via a specific high affinity receptor and enters the cytoplasm by clathrin-mediated endocytosis.