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.

Meta-analysis of natural, unnatural and cause-specific mortality rates following discharge from in-patient psychiatric facilities.

BACKGROUND: People discharged from in-patient psychiatric facilities have highly elevated rates of suicide, and there is increasing concern about natural mortality among the seriously mentally ill. METHOD: A meta-analysis of English-language, peer-reviewed longitudinal studies of mortality among patients discharged from in-patient psychiatric facilities was conducted using papers published in MEDLINE, PsycINFO or EMBASE (from 1 January 1960 to 1 April 2018) located using the terms ((suicid*).ti AND (hospital OR discharg* OR inpatient OR in-patient OR admit*)).ab and ((mortality OR outcome* OR death*) AND (psych* OR mental*)).ti AND (admit* OR admis* OR hospital* OR inpatient* OR in-patient* OR discharg*).ab. Pooled mortality rates for aggregated natural and unnatural causes, and the specific causes of suicide, accident, homicide, vascular, neoplastic, respiratory, gastrointestinal, infectious and metabolic death were calculated using a random-effects meta-analytic model. Between-study heterogeneity was investigated using subgroup analysis and metaregression. RESULTS: The pooled natural death rate of 1128 per 100 000 person-years exceeded the pooled unnatural deaths of 479 per 100 000 person-year among studies with varying periods of follow-up. Natural deaths significantly exceeded unnatural deaths among studies with a mean follow-up of longer than 2 years, and vascular deaths exceeded suicide deaths among studies with mean period of follow-up of 5 years or longer. CONCLUSION: Suicide may be the largest single cause of death in the short term after discharge from in-patient psychiatric facilities but vascular disease is the major cause of mortality in the medium- and long-term.

Suicide risk assessment among psychiatric inpatients: a systematic review and meta-analysis of high-risk categories.

BACKGROUND: The clinical care of psychiatric patients is often guided by perceptions of suicide risk. The aim of this study was to examine the methods and results of studies reporting high-risk models for inpatient suicide. METHODS: We conducted a registered meta-analysis according to PRISMA guidelines. We searched for relevant peer-reviewed cohort and controlled studies indexed in Medline, EMBASE and PsychINFO. RESULTS: The pooled odds ratio (OR) among 18 studies reporting high-risk models for inpatient suicide was 7.1 [95% confidence interval (CI) 4.2-12.2]. Between-study heterogeneity in ORs was very high (range 0-94.8, first quartile 3.4, median 8.8, third quartile 26.1, prediction interval 0.80-63.1, I2 = 88.1%). The meta-analytically derived sensitivity was 53.1% (95% CI 38.2-67.5%, I2 = 95.9%) and specificity was 84.2% (95% CI 71.6-91.9%, I2 = 99.9%) with an associated meta-analytic area under the curve of 0.83. The positive predictive value of risk categorization among six cohort studies was 0.43% (95% CI 0.014-1.3%, I2 = 95.9%). A history of suicidal behavior and depressive symptoms or affective disorder was included in the majority of high-risk models. CONCLUSIONS: Despite the strength of the pooled association between high-risk categorization and suicide, the very high degree of observed heterogeneity indicates uncertainty about our ability to meaningfully distinguish inpatients according to suicide risk. The limited sensitivity and low positive predictive value of risk categorization suggest that suicide risk models are not a suitable basis for clinical decisions in inpatient settings.

Meta-analysis examining the epidemiology of clozapine-associated neutropenia.

BACKGROUND: Clozapine is associated with life-threatening neutropenia. There are no previous meta-analyses of the epidemiology of clozapine-associated neutropenia. OBJECTIVES: To determine the cumulative incidence of mild, moderate and severe neutropenia, incidence of death related to severe neutropenia, case fatality rate of neutropenia and the longitudinal incidence of neutropenia following exposure to clozapine. DATA SOURCES: A systematic search of Medline, EMBASE and PsycINFO using search terms [clozapine OR clopine OR zaponex OR clozaril] AND [neutropenia OR agranulocytosis]. METHODS: Random effects meta-analysis to determine event rates and longitudinal incidence of events per 100 person-years of exposure. RESULTS: A total of 108 studies were included. The incidence of clozapine-associated neutropenia was 3.8% (95% CI: 2.7-5.2%) and severe neutropenia 0.9% (95% CI: 0.7-1.1%). The incidence of death related to neutropenia following prescription of clozapine was 0.013% (95% CI: 0.01-0.017%). The case fatality rate of severe neutropenia was 2.1% (95% CI: 1.6-2.8%). The peak incidence of severe neutropenia occurred at one month of exposure and declined to negligible levels after one year of treatment. CONCLUSION: Severe neutropenia associated with clozapine is a rare event and occurs early with a substantial decline in risk after one year of exposure. Death from clozapine-associated neutropenia is extremely rare. Implications for haematological monitoring are discussed.

Meta-analysis of suicide rates among psychiatric in-patients.

OBJECTIVE: To examine factors associated with the number of psychiatric admissions per in-patient suicide and the suicide rate per 100,000 in-patient years in psychiatric hospitals. METHOD: Random-effects meta-analysis was used to calculate pooled estimates, and meta-regression was used to examine between-sample heterogeneity. RESULTS: Forty-four studies published between 1945 and 2013 reported a total of 7552 in-patient suicides. The pooled estimate of the number of admissions per suicide calculated using 39 studies reporting 150 independent samples was 676 (95% CI: 604-755). Recent studies tended to report higher numbers of admissions per suicide than earlier studies. The pooled estimate of suicide rates per 100,000 in-patient years calculated using 27 studies reporting 95 independent samples was 147 (95% CI: 138-156). Rates of suicide per 100,000 in-patient years tended to be higher in more recent samples, in samples from regions with a higher whole of population suicide rate, in samples from settings with a shorter average length of hospital stay and in studies using coronial records to define suicide. CONCLUSION: Rates of in-patient suicide in psychiatric hospitals vary remarkably and are disturbingly high. Further research might clarify the extent to which patient factors and the characteristics of in-patient facilities contribute to the unacceptable mortality in psychiatric hospitals.

Meta-analysis of the association between suicidal ideation and later suicide among patients with either a schizophrenia spectrum psychosis or a mood disorder.

OBJECTIVE: Recent studies of patients with a mix of psychiatric diagnoses have suggested a modest or weak association between suicidal ideation and later suicide. The aim of this study was to examine the extent to which the association between expressed suicidal ideation and later suicide varies according to psychiatric diagnosis. METHOD: A systematic meta-analysis of studies that report the association between suicidal ideation and later suicide in patients with 'mood disorders', defined to include major depression, dysthymia and bipolar disorder, or 'schizophrenia spectrum psychosis', defined to include schizophrenia, schizophreniform disorder and delusional disorder. RESULTS: Suicidal ideation was strongly associated with suicide among patients with schizophrenia spectrum psychosis [14 studies reporting on 567 suicides, OR = 6.49, 95% confidence interval (CI) 3.82-11.02]. The association between suicidal ideation and suicide among patients with mood disorders (11 studies reporting on 860 suicides, OR = 1.49, 95% CI 0.92-2.42) was not significant. Diagnostic group made a significant contribution to between-study heterogeneity (Q-value = 16.2, df = 1, P < 0.001) indicating a significant difference in the strength of the associations between suicidal ideation and suicide between the two diagnostic groups. Meta-regression and multiple meta-regression suggested that methodological issues in the primary research did not explain the findings. Suicidal ideation was weakly but significantly associated with suicide among studies of patients with mood disorders over periods of follow-up of <10 years. CONCLUSION: Although our findings suggest that the association between suicidal ideation and later suicide is stronger in schizophrenia spectrum psychosis than in mood disorders this result should be interpreted cautiously due to the high degree of between-study heterogeneity and because studies that used stronger methods of reporting had a weaker association between suicidal ideation and suicide.

Suicide risk assessment: myth and reality.

To be, or not to be, that is the question - Whether 'tis nobler in the mind to suffer The slings and arrows of outrageous fortune, Or to take arms against a sea of troubles, And by opposing end them? To die, to sleep; … Hamlet, III i Hamlet's soliloquy is surely the most famous expression of suicidal ideation in English literature. However, by the end of the play, it is not Hamlet, but Ophelia who has taken her own life, even though she gave no prior hint of self-destruction.

Systematic meta-analysis of the risk factors for deliberate self-harm before and after treatment for first-episode psychosis.

OBJECTIVE: Attempted suicide and deliberate self-injury can occur before or after presentation with a first-episode of psychosis. The aim of the study is to identify the factors associated with suicide attempts or deliberate self-injury before and after treatment for first-episode psychosis. METHOD: A systematic review and meta-analysis of controlled studies of factors associated with either suicide attempts or deliberate self-injury, referred to here as deliberate self-harm (DSH). RESULTS: The pooled proportion of patients who reported DSH prior to treatment for first-episode psychosis was 18.4% (95% Confidence Interval (CI) 14.4-23.3, N = 18 studies, I(2) = 93.8). The pooled proportion of patients with DSH during the period of untreated psychosis was 9.8%, (95% CI 6.7-14.2, N = 5 studies, I(2) = 58.9). The pooled proportion of patients committing DSH during periods of follow up of between 1 and 7 years was 11.4%, (95% CI, 8.3-15.5, N = 13 studies, I(2) = 89.2). Categorical factors associated with an increased risk of DSH were a prior history of DSH (OR = 3.94), expressed suicide ideation (OR = 2.34), greater insight (OR = 1.64), alcohol abuse (OR = 1.68) and substance use (OR = 1.46). Continuous variables associated with an increased risk of DSH were younger age of onset (Standardized Mean Difference (SMD) = -0.28), younger age at first treatment (SMD = -0.18), depressed mood (SMD = 0.49) and the duration of untreated psychosis (SMD = 0.20). Depressed mood and substance use were associated with DSH both before and after treatment, negative symptoms were associated with DSH after treatment but not before treatment. Positive symptoms and social and global functioning were not associated with DSH. Younger age and the duration of untreated psychosis were associated with DSH before treatment but not after treatment. CONCLUSION: Earlier treatment of first-episode psychosis and successful treatment of depression and substance use could prevent some episodes of DSH and might reduce suicide mortality in early psychosis.

A systematic review and meta-regression analysis of aggression during the first episode of psychosis.

OBJECTIVE: The First Episode of Psychosis (FEP) represents a period of heightened risk for aggression. However, it is not known whether this risk is significantly altered following contact with mental health services. METHOD: Meta-analytic methods were used to estimate pooled prevalence of 'any' and 'serious' aggression during FEP, while meta-regression analyses were conducted to explore reasons for heterogeneity between studies. RESULTS: Fifteen studies comprising 3, 294 FEP subjects were analysed. Pooled prevalence of 'any aggression' before service contact was 28% (95% CI: 22-34) and following contact 31% (95% CI: 20-42). Pooled prevalence of 'serious aggression' was 16% (95% CI: 11-20) before service contact and 13% (95% CI: 6-20) following contact. Four studies reporting repeated assessments within the same cohort revealed that aggression rates did not significantly differ post and pre service contact: Odds Ratios for any aggression: 1.18 (95% CI: 0.46-2.99) and serious aggression: 0.61 (95% CI: 0.31-1.21). CONCLUSION: Rates of aggression are high during FEP, both before and following initial service contact, and seem not to alter following contact. This conclusion remains tentative due to considerable heterogeneity between studies and a lack of prospective cohort studies.

The chiral structure of porous chitin within the wing-scales of Callophrys rubi.

The structure of the porous three-dimensional reticulated pattern in the wing scales of the butterfly Callophrys rubi (the Green Hairstreak) is explored in detail, via scanning and transmission electron microscopy. A full 3D tomographic reconstruction of a section of this material reveals that the predominantly chitin material is assembled in the wing scale to form a structure whose geometry bears a remarkable correspondence to the srs net, well-known in solid state chemistry and soft materials science. The porous solid is bounded to an excellent approximation by a parallel surface to the Gyroid, a three-periodic minimal surface with cubic crystallographic symmetry I4132, as foreshadowed by Stavenga and Michielson. The scale of the structure is commensurate with the wavelength of visible light, with an edge of the conventional cubic unit cell of the parallel-Gyroid of approximately 310 nm. The genesis of this structure is discussed, and we suggest it affords a remarkable example of templating of a chiral material via soft matter, analogous to the formation of mesoporous silica via surfactant assemblies in solution. In the butterfly, the templating is achieved by the lipid-protein membranes within the smooth endoplasmic reticulum (while it remains in the chrysalis), that likely form cubic membranes, folded according to the form of the Gyroid. The subsequent formation of the chiral hard chitin framework is suggested to be driven by the gradual polymerisation of the chitin precursors, whose inherent chiral assembly in solution (during growth) promotes the formation of a single enantiomer.

Systematic review and meta-analysis of the clinical factors associated with the suicide of psychiatric in-patients.

OBJECTIVE: To estimate the strength of the associations between the suicide of psychiatric in-patients and demographic, historical, symptomatic, diagnostic and treatment factors. METHOD: A systematic review and meta-analysis of controlled studies of the suicide of psychiatric in-patients including suicides while on approved or unapproved leave. RESULTS: Factors that were significantly associated with in-patient suicide included a history of deliberate self-harm, hopelessness, feelings of guilt or inadequacy, depressed mood, suicidal ideas and a family history of suicide. Patients suffering from both schizophrenia and depressed mood appeared to be at particular risk. The association between suicidal ideas and in-patient suicide was weak and did not reach statistical significance after a quantitative correction for publication bias. A high-risk categorization as defined by a combination of retrospectively determined individual risk factors was strongly statistically associated with in-patient suicide (OR=10.9), with a sensitivity of 64% and a specificity of 85%. CONCLUSION: Despite the apparently strong association between high-risk categorization and subsequent suicide, the low base rate of in-patient suicide means that predictive value of a high-risk categorization is below 2%. The development of safer hospital environments and improved systems of care are more likely to reduce the suicide of psychiatric in-patients than risk assessment.

Potentially preventable hospitalisations for physical health conditions in community mental health service users: a population-wide linkage study.

AIMS: Mental health (MH) service users have increased prevalence of chronic physical conditions such as cardio-respiratory diseases and diabetes. Potentially Preventable Hospitalisations (PPH) for physical health conditions are an indicator of health service access, integration and effectiveness, and are elevated in long term studies of people with MH conditions. We aimed to examine whether PPH rates were elevated in MH service users over a 12-month follow-up period more suitable for routine health indicator reporting. We also examined whether MH service users had increased PPH rates at a younger age, potentially reflecting the younger onset of chronic physical conditions. METHODS: A population-wide data linkage in New South Wales (NSW), Australia, population 7.8 million. PPH rates in 178 009 people using community MH services in 2016-2017 were compared to population rates. Primary outcomes were crude and age- and disadvantage-standardised annual PPH episode rate (episodes per 100 000 population), PPH day rate (hospital days per 100 000) and adjusted incidence rate ratios (AIRR). RESULTS: MH service users had higher rates of PPH admission (AIRR 3.6, 95% CI 3.5-3.6) and a larger number of hospital days (AIRR 5.2, 95% CI 5.2-5.3) than other NSW residents due to increased likelihood of admission, more admissions per person and longer length of stay. Increases were greatest for vaccine-preventable conditions (AIRR 4.7, 95% CI 4.5-5.0), and chronic conditions (AIRR 3.7, 95% CI 3.6-3.7). The highest number of admissions and relative risks were for respiratory and metabolic conditions, including chronic obstructive airways disease (AIRR 5.8, 95% CI 5.5-6.0) and diabetic complications (AIRR 5.4, 95% CI 5.1-5.8). One-quarter of excess potentially preventable bed days in MH service users were due to vaccine-related conditions, including vaccine-preventable respiratory illness. Age-related increases in risk occurred earlier in MH service users, particularly for chronic and vaccine-preventable conditions. PPH rates in MH service users aged 20-29 were similar to population rates of people aged 60 and over. These substantial differences were not explained by socio-economic disadvantage. CONCLUSIONS: PPHs for physical health conditions are substantially increased in people with MH conditions. Short term (12-month) PPH rates may be a useful lead indicator of increased physical morbidity and less accessible, integrated or effective health care. High hospitalisation rates for vaccine-preventable respiratory infections and hepatitis underline the importance of vaccination in MH service users and suggests potential benefits of prioritising this group for COVID-19 vaccination.

The danger of dangerousness: why we must remove the dangerousness criterion from our mental health acts.

OBJECTIVES: The mental health legislation of most developed countries includes either a dangerousness criterion or an obligatory dangerousness criterion (ODC). A dangerousness criterion holds that mentally ill people may be given treatment without consent if they are deemed to be a risk to themselves or others. An ODC holds that mentally ill people may be given treatment without consent only if they are deemed to be a risk to themselves or others. This paper argues that the dangerousness criterion is unnecessary, unethical and, in the case of the ODC, potentially harmful to mentally ill people and to the rest of the community. METHODS: We examine the history of the dangerousness criterion, and provide reasoned argument and empirical evidence in support of our position. RESULTS: Dangerousness criteria are not required to balance the perceived loss of autonomy arising from mental health legislation. Dangerousness criteria unfairly discriminate against the mentally ill, as they represent an unreasonable barrier to treatment without consent, and they spread the burden of risk that any mentally ill person might become violent across large numbers of mentally ill people who will never become violent. Mental health legislation that includes an ODC is associated with a longer duration of untreated psychosis, and probably contributes to a poorer prognosis and an increase risk of suicide and violence in patients in their first episode of psychosis. CONCLUSIONS: Dangerousness criteria should be removed from mental health legislation and be replaced by criteria that focus on a patient's capacity to refuse treatment.

Selective coating of holes in microstructured optical fiber and its application to in-fiber absorptive polarizers.

An interesting feature of microstructured optical fibers (MOFs) is that their properties can be adjusted by filling or coating of the holes. Some applications require selective filling or coating, which has proved experimentally demanding. We demonstrate selective coating of MOFs with metal and use it to fabricate an in-fiber absorptive polarizer.

Liquid-filled hollow core microstructured polymer optical fiber.

Guidance in a liquid core is possible with microstructured optical fibers, opening up many possibilities for chemical and biochemical fiber-optic sensing. In this work we demonstrate how the bandgaps of a hollow core microstructured polymer optical fiber scale with the refractive index of liquid introduced into the holes of the microstructure. Such a fiber is then filled with an aqueous solution of (-)-fructose, and the resulting optical rotation measured. Hence, we show that hollow core microstructured polymer optical fibers can be used for sensing, whilst also fabricating a chiral optical fiber based on material chirality, which has many applications in its own right.

Stable imprinting of long-period gratings in microstructured polymer optical fibre.

A simple heat imprinting method for producing stable long-period gratings (LPGs) in microstructured polymer optical fibre (mPOF) is presented as well as the examination of their lifetime and the modelling results of these gratings. Writing LPGs in mPOF presents opportunities for sensors in fibre that can withstand greater bending and strain and are adaptable to specific applications through modification of the cladding structure.

Inhibition of gamma-glutamyl transpeptidase activity by acivicin in vivo protects the kidney from cisplatin-induced toxicity.

Cisplatin [cis-dichlorodiammineplatinum(II)] is a widely used chemotherapeutic drug that is toxic to the proximal tubule cells of the kidney. gamma-Glutamyl transpeptidase (GGT) is localized to the luminal surface of the renal proximal tubules. GGT catalyzes the initial step in the metabolism of glutathione-conjugated drugs to mercapturic acids, some of which are severely nephrotoxic. We proposed that the nephrotoxicity of cisplatin was dependent on the cleavage of a cisplatin-glutathione conjugate by GGT. To test this hypothesis, renal GGT activity was blocked in male Sprague-Dawley rats by acivicin, a non-competitive inhibitor of GGT. Treatment with cisplatin alone caused extensive acute necrosis of the proximal tubules, but the proximal tubule cells appeared normal in rats treated with acivicin prior to cisplatin. Blood urea nitrogen and serum creatinine levels confirmed the protective effect of acivicin. Glutathione is a physiological substrate for GGT. Administration of an 83-fold excess of glutathione 30 min prior to cisplatin also inhibited cisplatin-induced nephrotoxicity. These data provide important new evidence that a large bolus of glutathione blocks the nephrotoxicity of cisplatin by competitively inhibiting GGT. These results indicate that cisplatin is conjugated to glutathione in vivo. The platinum-glutathione conjugate is nontoxic until metabolized by the proximal tubule cells. Formation of the nephrotoxic derivative of cisplatin requires GGT activity.

Right medial thalamic lesion causes isolated retrograde amnesia.

Pervasive retrograde amnesia without anterograde memory impairment has rarely been described as a consequence of circumscribed brain damage. We report this phenomenon in a 33 yr-old, right-handed man (JG) in association with the extension in the right thalamus of a previously small, bilateral thalamic lesion. JG presented with a dense amnesia for autobiographical material more than a few years old, with some sparing of recent memories. Furthermore, he was completely unable to recognise famous people or world events. Many other aspects of semantic knowledge were intact and there was no evidence of general intellectual impairment, executive dysfunction or loss of visual imagery. Magnetic resonance imaging revealed an acute lesion in the right thalamus and two small, symmetrical, bilateral non-acute thalamic lesions. Follow-up neuropsychological assessment indicated a stable pattern of impaired retrograde and spared anterograde memory over 18 months and psychiatric assessments yielded no evidence of confabulation, malingering or other symptoms to suggest psychogenic amnesia. JG's profile indicates that the division of declarative memory into just two categories - episodic and semantic - is inadequate. Rather, his case adds to the growing body evidence to suggest that world knowledge pertaining to people and events is stored or accessed similarly to autobiographical information and differently from other types of more general factual knowledge. We hypothesize that the right mediodorsal thalamic nucleus and immediately surrounding regions comprise the central processing mechanism referred to by McClelland (Revue Neurologique, 150 (1994) 570) and Markowitsch (Brain Research Review, 21 (1995) 117) as responsible for inducing and co-ordinating the recall of these sorts of cortically stored memory engrams.