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.

Phase I/II trial of cabazitaxel plus abiraterone in patients with metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel and abiraterone.

Background: Abiraterone and cabazitaxel improve survival in patients with metastatic castration-resistant prostate cancer (mCRPC). We conducted an open-label phase I/II trial of cabazitaxel plus abiraterone to assess the antitumor activity and tolerability in patients with progressive mCRPC after docetaxel (phase I), and after docetaxel and abiraterone (phase II) (NCT01511536). Patients and methods: The primary objectives were to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of cabazitaxel plus abiraterone (phase I), and the prostate-specific antigen (PSA) response defined as a ≥ 50% decrease confirmed ≥3 weeks later with this combination (phase II). Results: Ten patients were enrolled in the phase I component; nine were evaluable. No DLTs were identified. The MTD was established as the approved doses for both drugs (cabazitaxel 25 mg/m2 every 3 weeks and abiraterone 1000 mg once daily). Daily abiraterone treatment did not impact on cabazitaxel clearance. Twenty-seven patients received cabazitaxel plus abiraterone plus prednisone (5 mg twice daily) in phase II. The median number of cycles administered (cabazitaxel) was seven (range: 1-28). Grade 3-4 treatment-emergent adverse events included asthenia (in 5 patients; 14%), neutropenia (in 5 patients; 14%) and diarrhea (in 3 patients; 8%). Nine patients (24%) required dose reductions of cabazitaxel. Of 26 evaluable patients, 12 achieved a PSA response [46%; 95% confidence interval (CI): 26.6-66.6%]. Median PSA-progression-free survival was 6.9 months (95% CI: 4.1-10.3 months). Of 14 patients with measurable disease at baseline, 3 (21%) achieved a partial response per response evaluation criteria in solid tumors. Conclusions: The combination of cabazitaxel and abiraterone has a manageable safety profile and shows antitumor activity in patients previously treated with docetaxel and abiraterone.

Androgen receptor mutations in patients with castration-resistant prostate cancer treated with apalutamide.

BACKGROUND: Mutations in the androgen receptor (AR) ligand-binding domain (LBD), such as F877L and T878A, have been associated with resistance to next-generation AR-directed therapies. ARN-509-001 was a phase I/II study that evaluated apalutamide activity in castration-resistant prostate cancer (CRPC). Here, we evaluated the type and frequency of 11 relevant AR-LBD mutations in apalutamide-treated CRPC patients. PATIENTS AND METHODS: Blood samples from men with nonmetastatic CRPC (nmCRPC) and metastatic CRPC (mCRPC) pre- or post-abiraterone acetate and prednisone (AAP) treatment (≥6 months' exposure) were evaluated at baseline and disease progression in trial ARN-509-001. Mutations were detected in circulating tumor DNA using a digital polymerase chain reaction-based method known as BEAMing (beads, emulsification, amplification and magnetics) (Sysmex Inostics' GmbH). RESULTS: Of the 97 total patients, 51 had nmCRPC, 25 had AAP-naïve mCRPC, and 21 had post-AAP mCRPC. Ninety-three were assessable for the mutation analysis at baseline and 82 of the 93 at progression. The overall frequency of detected AR mutations at baseline was 7/93 (7.5%) and at progression was 6/82 (7.3%). Three of the 82 (3.7%) mCRPC patients (2 AAP-naïve and 1 post-AAP) acquired AR F877L during apalutamide treatment. At baseline, 3 of the 93 (3.2%) post-AAP patients had detectable AR T878A, which was lost after apalutamide treatment in 1 patient who continued apalutamide treatment for 12 months. CONCLUSIONS: The overall frequency of detected mutations at baseline (7.5%) and progression (7.3%) using the sensitive BEAMing assay was low, suggesting that, based on this assay, AR-LBD mutations such as F877L and T878A are not common contributors to de novo or acquired resistance to apalutamide. CLINICALTRIALS.GOV IDENTIFIER: NCT01171898.

Does Gleason score at initial diagnosis predict efficacy of abiraterone acetate therapy in patients with metastatic castration-resistant prostate cancer? An analysis of abiraterone acetate phase III trials.

BACKGROUND: The usefulness of Gleason score (<8 or ≥8) at initial diagnosis as a predictive marker of response to abiraterone acetate (AA) plus prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) was explored retrospectively. PATIENTS AND METHODS: Initial diagnosis Gleason score was obtained in 1048 of 1195 (COU-AA-301, post-docetaxel) and 996 of 1088 (COU-AA-302, chemotherapy-naïve) patients treated with AA 1 g plus prednisone 5 mg twice daily by mouth or placebo plus prednisone. Efficacy end points included radiographic progression-free survival (rPFS) and overall survival (OS). Distributions and medians were estimated by Kaplan-Meier method and hazard ratio (HR) and 95% confidence interval (CI) by Cox model. RESULTS: Baseline characteristics were similar across studies and treatment groups. Regardless of Gleason score, AA treatment significantly improved rPFS in post-docetaxel [Gleason score <8: median, 6.4 versus 5.5 months (HR = 0.70; 95% CI 0.56-0.86), P = 0.0009 and Gleason score ≥8: median, 5.6 versus 2.9 months (HR = 0.58; 95% CI 0.48-0.72), P < 0.0001] and chemotherapy-naïve patients [Gleason score <8: median, 16.5 versus 8.2 months (HR = 0.50; 95% CI 0.40-0.62), P < 0.0001 and Gleason score ≥8: median, 13.8 versus 8.2 months (HR = 0.61; 95% CI 0.49-0.76), P < 0.0001]. Clinical benefit of AA treatment was also observed for OS, prostate-specific antigen (PSA) response, objective response and time to PSA progression across studies and Gleason score subgroups. CONCLUSION: OS and rPFS trends demonstrate AA treatment benefit in patients with pre- or post-chemotherapy mCRPC regardless of Gleason score at initial diagnosis. The initial diagnostic Gleason score in patients with mCRPC should not be considered in the decision to treat with AA, as tumour metastases may no longer reflect the histology at the time of diagnosis. CLINICAL TRIALS NUMBER: COU-AA-301 (NCT00638690); COU-AA-302 (NCT00887198).

A prognostic index model for predicting overall survival in patients with metastatic castration-resistant prostate cancer treated with abiraterone acetate after docetaxel.

BACKGROUND: Few prognostic models for overall survival (OS) are available for patients with metastatic castration-resistant prostate cancer (mCRPC) treated with recently approved agents. We developed a prognostic index model using readily available clinical and laboratory factors from a phase III trial of abiraterone acetate (hereafter abiraterone) in combination with prednisone in post-docetaxel mCRPC. PATIENTS AND METHODS: Baseline data were available from 762 patients treated with abiraterone-prednisone. Factors were assessed for association with OS through a univariate Cox model and used in a multivariate Cox model with a stepwise procedure to identify those of significance. Data were validated using an independent, external, population-based cohort. RESULTS: Six risk factors individually associated with poor prognosis were included in the final model: lactate dehydrogenase > upper limit of normal (ULN) [hazard ratio (HR) = 2.31], Eastern Cooperative Oncology Group performance status of 2 (HR = 2.19), presence of liver metastases (HR = 2.00), albumin ≤4 g/dl (HR = 1.54), alkaline phosphatase > ULN (HR = 1.38) and time from start of initial androgen-deprivation therapy to start of treatment ≤36 months (HR = 1.30). Patients were categorized into good (n = 369, 46%), intermediate (n = 321, 40%) and poor (n = 107, 13%) prognosis groups based on the number of risk factors and relative HRs. The C-index was 0.70 ± 0.014. The model was validated by the external dataset (n = 286). CONCLUSION: This analysis identified six factors used to model survival in mCRPC and categorized patients into three distinct risk groups. Prognostic stratification with this model could assist clinical practice decisions for follow-up and monitoring, and may aid in clinical trial design. TRIAL REGISTRATION NUMBERS: NCT00638690.

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.

Risk for stroke and myocardial infarction with abiraterone versus enzalutamide in metastatic prostate cancer patients.

BACKGROUND: Abiraterone and enzalutamide use is associated with significant cardiovascular (CV) morbidity in clinical trials, but the magnitude and clinical relevance of this association in real-world prostate cancer (PC) population remain unknown. MATERIALS AND METHODS: We retrospectively reviewed the MarketScan claims databases (1 January 2013 to 30 September 2018) to identify adults with diagnosis of metastatic PC who received treatment with androgen deprivation therapy (ADT) and novel antiandrogen agents (abiraterone or enzalutamide). The primary CV outcome measure was composite outcome of acute myocardial infarction (MI) or stroke. Secondary outcomes were individual risks of MI or stroke. We used an intention-to-treat approach to analyze the CV outcomes associated with drug exposure among patients with metastatic PC. Cox regression model was used to estimate the independent association of two drugs with CV risk after adjustment for age, baseline atrial fibrillation, and Charlson Comorbidity Index. RESULTS: A total of 6294 patients with metastatic PC who were treated with ADT and either abiraterone or enzalutamide were included in the final analysis. Of these, 4017 (63.8%) patients used abiraterone and 2217 (32.2%) patients used enzalutamide. During the study period, 255 (6.3%) primary endpoint events occurred, resulting in an incidence rate of 4.3 per 100 patient-years. In multivariable analysis, abiraterone use was associated with a 31% increased risk of MI or stroke compared to enzalutamide (hazard ratio 1.31; 95% confidence interval 1.05-1.63; P = 0.01). The incidence rate was similar in patients who switched initial therapy from abiraterone to enzalutamide or vice versa (5.0 versus 5.6 per 100 patient-years, respectively). CONCLUSIONS: To our knowledge, this is the first real-world assessment of MI and stroke among metastatic PC patients receiving novel anti-androgens. Our findings of increased MI and stroke risk with abiraterone compared with enzalutamide are consistent with data from clinical trials and suggest that enzalutamide may be preferable for prostate cancer patients at high CV risk.

Single Question in Delirium (SQiD): testing its efficacy against psychiatrist interview, the Confusion Assessment Method and the Memorial Delirium Assessment Scale.

UNLABELLED: In this study we address the research question; How sensitive is a single question in delirium case finding? Of 33 'target' admissions, consent was obtained from 21 patients. The single question: 'Do you think [name of patient] has been more confused lately?' was put to friend or family. Results of the Single Question in Delirium (SQiD) were compared to psychiatrist interview (ΨI) which was the reference standard. The Confusion Assessment Method (CAM) and two other tools were also applied. Compared with ΨI, the SQiD achieved a sensitivity and specificity of 80% (95% CI 28.3-99.49%) and 71% (41.90-91.61%) respectively. The CAM demonstrated a negative predictive value (NPV) of 80% (51.91-95.67%) and the SQiD showed a NPV of 91% (58.72-99.77%). Kappa correlation of SQiD with the ΨI was 0.431 (p = 0.023). The CAM had a kappa value of 0.37 (p = 0.050). A further important finding in our study was that the CAM had only 40% sensitivity in the hands of minimally trained clinical users. CONCLUSION: The SQiD demonstrates potential as a simple clinical tool worthy or further investigation.

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.

Androgen deprivation therapy in locally advanced and metastatic prostate cancer.

Numerous studies have been performed testing the efficacy of early androgen deprivation (AD) in patients with localized and locally advanced prostate cancer. A systematic review of recent publications that report on the use of AD in non-metastatic prostate cancer patients was performed. Recently published mature randomized trials of AD plus local therapy were evaluated plus 2 large datasets on the use of AD for patients with serologic relapse after local therapy. Four mature randomized studies demonstrate an overall survival benefit to the use of AD in conjunction with definitive local therapy (3 with radiation and 1 with surgery). One retrospective analysis suggests that AD administered at early after serologic progression improves overall survival, and one retrospective analysis shows a reduction in metastasis-free survival but has not yet shown an overall survival benefit. In virtually all analyses, patients with high-risk features benefited from early AD when compared to deferred therapy. Consideration of AD is therefore warranted early in the clinical course of high-risk patients.

An analysis of nurses' post-incident manual restraint reports.

Manual restraint techniques are associated with the management of violence in psychiatric settings. Restraint effectiveness and acceptability are under scrutiny, yet the nature and frequency of who or what were involved in restraint episodes have not previously been fully described or understood. The aim of this study was to describe the nature and frequency of manual restraint-related events and their components. This study was carried out using content analyses of nurses' post-incident reports from a psychiatric unit situated within a general hospital, and from its associated medium-secure unit. Requests for restraint occurred at the rate of about once per day, and the majority related to patients' ill-directed frustration, resistance to containment and their desire to leave the ward. Only half of responses to conflicts resulted in restraint implementation. The majority of restraint activities occurred during the afternoon and night. Male patients and detained patients were more frequent participants in restraint interventions. To a lesser extent, police, ambulance, fire services, hospital security, visitors and ex-patients were also involved in restraint episodes. Injuries were rare. In conclusion, training in restraint skills, clinical audit of adverse incidents, and research into psychiatric aggression all need to take into account the association of restraint with the enforcement of detention and treatment of acutely ill patients. The coupling of restraint with medication requires examination of its safety and efficacy. Interagency training may enable the essential services involved to coordinate restraint activities more effectively.

Duranta erecta poisoning in nine dogs and a cat.

Four incidents of Duranta erecta (golden dewdrop, Sheena's Gold, Geisha Girl) poisoning affecting nine dogs and a cat produced drowsiness, hyperaesthesia and tetanic seizures in all affected animals with evidence of alimentary tract irritation (vomiting, gastric and intestinal haemorrhage, diarrhoea, melaena) in five dogs and the cat. Fruits and leaves were seen to be eaten by affected animals. Therapy was successful in three of the dogs. Repeated diazepam doses and, in some cases, additional pentobarbitone or propofol anaesthesia, were successful in controlling seizures.

Intensive care unit syndrome: a dangerous misnomer.

The terms intensive care unit (ICU) syndrome and ICU psychosis have been used interchangeably to describe a cluster of psychiatric symptoms that are unique to the ICU environment. It is often postulated that aspects of the ICU, such as sleep deprivation and sensory overload or monotony, are causes of the syndrome. This article reviews the empirical support for these propositions. We conclude that ICU syndrome does not differ from delirium and that ICU syndrome is caused exclusively by organic stressors on the central nervous system. We argue further that the term ICU syndrome is dangerous because it impedes standardized communication and research and may reduce the vigilance necessary to promptly investigate and reverse the medical cause of the delirium. Directions for future research are suggested.

Coercive manoeuvres in a psychiatric intensive care unit.

Coercive manoeuvres in a psychiatric intensive care unit The practice of physical restraint techniques in the management of disturbed behaviour is a significant part of the role of mental health nurses, particularly in Psychiatric Intensive Care Units (PICUs). Debate about what constitutes good practice is intense, and the subject of recently issued guidelines by National Institute for Mental Health in England. However, the contribution of other forms of conflict management techniques has tended to be ignored. The purpose of this study was to identify, describe and categorize coercive manoeuvres used by nurses, and to examine the circumstances and appropriateness of their use. Non-participant observation of verbal and non-verbal interaction between patients and nurses during conflict situations was undertaken on one PICU. The critical incidents observed were identified, categorized and systematically recorded. Nurses used a variety of low level physical and interactional manoeuvres in order to manage patients' disturbed and resistive behaviour. These manoeuvres were seldom recorded, discussed or reviewed, although they were frequently used to manage critical conflict situations. These manoeuvres have neither been previously described nor evaluated. They may, in some cases, be useful substitutes for actual restraint, alternatively they may, in some cases, be judged undesirable. It is not known how widespread these practices are in acute psychiatry.

Dietary patterns, gastrointestinal complaints, and nutrition knowledge of recreational triathletes.

Dietary habits, nutrition knowledge, and gastrointestinal complaints were evaluated in 21 female and 50 male triathletes; 30 completed hemoccult slides to determine the frequency of gastrointestinal bleeding. Triathletes trained 11 h/wk with weekly distances of 5.3, 116.5, and 40.9 km for swimming, biking, and running, respectively. Mean daily energy intake averaged 9058 and 11,591 kJ for women and men, respectively; 53.8% of the energy was from carbohydrates. Mean intakes of vitamins and most minerals exceeded the Recommended Dietary Allowances (RDAs), but many had intakes below RDAs for some nutrients; greater than 60% had low zinc and copper intakes. Because 39% took a daily multivitamin-mineral supplement, some had intakes 200-600% above the RDA. Although there were notable misconceptions about nutrition, nutrition knowledge was high. Upper-gastrointestinal complaints, reported by 50%, included bloating and abdominal gas; the incidence of positive hemoccult slides was 27%. The relation among performance, dietary patterns, nutrition knowledge, and gastrointestinal function remains to be established.

Bioreactor for a larger scale hepatocyte in vitro perfusion.

A bioreactor construction for hepatocytes and liver sinusoidal endothelial cells is described. The reactor is based on capillaries for hepatocyte immobilization. Four discrete capillary membrane systems, each serving different purposes, are woven to create a three-dimensional framework for decentralized cell perfusion with low metabolite gradients and decentralized oxygenation and CO2 removal. The biochemical performance of reactors initially seeded with 2.5 x 10(9) hepatocytes were evaluated over 3 weeks. On day 21, pig albumin synthesis was 4.7 mg/day, lidocaine metabolism was 813.7 +/- 23 micrograms/hr, galactose elimination was 210.1 +/- 3 mg/hr, and midazolam metabolism was 37.1 +/- 2 micrograms/hr. The specific construction of the reactor enables scale-up to hybrid liver support systems as extracorporeal bridging devices for liver transplantation.

The outcome of patients with pleural effusion of indeterminate cause at thoracotomy.

In 51 patients, the cause for pleural effusion remained indeterminate immediately after thoracotomy. Thirty-one (60.8%) had no recurrence of the effusion, and no cause became apparent during a follow-up period of from 1 1/2 to 15 years. Two patients (3.9%) died relatively soon after thoracotomy, but death was not clearly related to the pleural effusion. In 18 patients (35.3%), the cause of the effusion became apparent from 12 days to 6 years after thoracotomy. In 13 of these 18 patients, malignancy (6 patients with lymphoma, 4 with malignant pleural mesothelioma, and 3 with other malignancy) was ultimately diagnosed. In 3 of the 18 patients, the ultimate diagnosis was a collagen-vascular disease, and 1 patient each had the yellow-nail syndrome and mitral stenosis.