Psilocybin for dementia prevention? The potential role of psilocybin to alter mechanisms associated with major depression and neurodegenerative diseases.

Major depression is an established risk factor for subsequent dementia, and depression in late life may also represent a prodromal state of dementia. Considering current challenges in the clinical development of disease modifying therapies for dementia, the focus of research is shifting towards prevention and modification of risk factors to alter the neurodegenerative disease trajectory. Understanding mechanistic commonalities underlying affective symptoms and cognitive decline may reveal biomarkers to aid early identification of those at risk of progressing to dementia during the preclinical phase of disease, thus allowing for timely intervention. Adult hippocampal neurogenesis (AHN) is a phenomenon that describes the birth of new neurons in the dentate gyrus throughout life and it is associated with spatial learning, memory and mood regulation. Microglia are innate immune system macrophages in the central nervous system that carefully regulate AHN via multiple mechanisms. Disruption in AHN is associated with both dementia and major depression and microgliosis is a hallmark of several neurodegenerative diseases. Emerging evidence suggests that psychedelics promote neuroplasticity, including neurogenesis, and may also be immunomodulatory. In this context, psilocybin, a serotonergic agonist with rapid-acting antidepressant properties has the potential to ameliorate intersecting pathophysiological processes relevant for both major depression and neurodegenerative diseases. In this narrative review, we focus on the evidence base for the effects of psilocybin on adult hippocampal neurogenesis and microglial form and function; which may suggest that psilocybin has the potential to modulate multiple mechanisms of action, and may have implications in altering the progression from major depression to dementia in those at risk.

Antidepressant and antipsychotic side-effects and personalised prescribing: a systematic review and digital tool development.

BACKGROUND: Side-effects of psychiatric medication impair quality of life and functioning. Furthermore, they contribute to morbidity, mortality, stigma, and poor treatment concordance resulting in relapse of psychiatric illness. Guidelines recommend discussing side-effects with patients when making treatment decisions, but a synthesis of antidepressant and antipsychotic side-effects to guide this process is missing, and considering all side-effects is a complex, multidimensional process. We aimed to create comprehensive databases of antipsychotic and antidepressant side-effects, and a digital tool to support database navigation. METHODS: To create the databases, we did an umbrella review of Embase, PsycINFO, and MEDLINE from database inception to June 26, 2023. We included meta-analyses of randomised controlled trials examining antipsychotic monotherapy in the treatment of schizophrenia or antidepressant monotherapy in the treatment of major depressive disorder. We included meta-analyses in adults (aged ≥18 years) that assessed drugs with a common comparator. The search was complemented by a review of national and international guidelines and consensus statements for the treatment of major depressive disorder and schizophrenia in adults. Effect sizes for antipsychotic and antidepressant side-effects were extracted from meta-analyses examining the largest number of drugs. In cases of incomplete meta-analytic coverage, data were imputed on the basis of guideline-derived ordinal rankings or, if imputation was not possible, ordinal scores were extracted. Both meta-analytic and ordinal outcomes were normalised to provide values between 0 and 1. We then constructed a digital tool, the Psymatik Treatment Optimizer, to combine the side-effect databases with side-effect concerns of an individual user, to enable users to select side-effects of concern and the relative degree of concern for each side-effect. Concern weightings and the side-effect databases are synthesised via a multicriteria decision analysis method (technique for order of preference by similarity to ideal situation, or TOPSIS). FINDINGS: Of 3724 citations, 14 articles containing 68 meta-analyses of individual side-effects met inclusion criteria. After review of 19 guidelines, seven provided ordinal data. Antipsychotic data were extracted from five studies (11 meta-analyses, n=65 594 patients) and four guidelines, and antidepressant data were extracted from three guidelines. The resultant databases included data on 32 antipsychotics (14 side-effects) and 37 antidepressants (nine side-effects). The databases highlighted the clinical dilemma associated with balancing side-effects, with avoidance of one side-effect (eg, weight gain for antipsychotics) increasing the risk of others (eg, akathisia). To aid with this dilemma, the Psymatik Treatment Optimizer synthesises the side-effect databases with individual user-defined concern weights. After computing up to 5851 pairwise comparisons for antidepressants and 5142 pairwise comparisons for antipsychotics, Psymatik ranks treatments in order of preference for the individual user, with the output presented in a heatmap. INTERPRETATION: By facilitating collaborative, personalised, and evidence-based prescribing decisions, the side-effect databases and digital application supports care delivery that is consistent with international regulatory guidance for the treatment of schizophrenia and depression, and it therefore has promise for informing psychiatric practice and improving outcomes. FUNDING: National Institute for Health and Care Research, Maudsley Charity, Wellcome Trust, Medical Research Council.

Implementing gradual, hyperbolic tapering of long-acting injectable antipsychotics by prolonging the inter-dose interval: an in silico modelling study.

Gradual, hyperbolic tapering has been proposed as a method to reduce the risk of withdrawal effects and potential relapse of an underlying condition by minimising disruption of existing equilibria. We applied hyperbolic tapering principles in silico to long-acting aripiprazole to generate regimens for withdrawal in clinical practice. We derived thresholds for taper rates using existing studies and consensus. Using pharmacokinetic data for aripiprazole long-acting injectable antipsychotic (ALAI), we conducted in silico modelling to examine the impact of abrupt cessation of long-acting injectable antipsychotic (LAI) medication and the effect of prolonging inter-dose interval on plasma aripiprazole levels and consequent D2 occupancy. We also modelled transitions from LAI medication to oral medication. Regimens were designed to afford a rate of reduction between 5 and 12.5 percentage points of D2 occupancy per month. Abrupt discontinuation of ALAI was shown to lead to a maximal D2 occupancy reduction of 16.8 percentage points per month; prolongation of the inter-dose interval of ALAI produced a slower reduction. Specifically, hyperbolic tapering was afforded by prolongation of a 400 mg ALAI inter-dose interval from 4 to 7 weeks, before reducing the dose to 300 mg ALAI. This could then be administered at up to 4-week (for 6% maximal D2 occupancy change), 6-week (9% change) or 7-week (11% change) intervals. Switching to oral medication - 5, 2.5 and 1.25 mg for the three regimens, respectively - is required for ALAI to complete full cessation to prevent too rapid a reduction in D2 occupancy. Oral medication should probably be maintained at a consistent dose for 3-6 months before further reductions to account for residual LAI being concurrently eliminated. Hyperbolic dose tapering is possible with ALAI through prolongation of the inter-dose interval and may reduce the risk of relapse compared to abrupt discontinuation of LAI medication.

Data-Driven Taxonomy for Antipsychotic Medication: A New Classification System.

BACKGROUND: Globally, there are more than 25 licensed antipsychotic medications. Antipsychotics are commonly described as either typical or atypical, but this dichotomous classification does not reflect the diversity of their pharmacological and clinical profiles. There is a need for a data-driven antipsychotic classification scheme suitable for clinicians and researchers that maps onto both pharmacological and clinical effects. Receptor affinity provides one starting point for such a scheme. METHODS: We analyzed affinities of 27 antipsychotics for 42 receptors from 3325 in vitro receptor binding studies. We used a clustering algorithm to group antipsychotics based on receptor affinity. Using a machine learning model, we examined the ability of this grouping to predict antipsychotic-induced clinical effects quantified according to an umbrella review of clinical trial and treatment guideline data. RESULTS: Clustering resulted in 4 groups of antipsychotics. The predominant receptor affinity and clinical effect "fingerprints" of these 4 groups were defined as follows: group 1, muscarinic (M2-M5) receptor antagonism (cholinergic and metabolic side effects); group 2, dopamine (D2) partial agonism and adrenergic antagonism (overall low side-effect burden); group 3, serotonergic and dopaminergic antagonism (overall moderate side-effect burden); and group 4, dopaminergic antagonism (extrapyramidal side effects and hyperprolactinemia). Groups 1 and 4 were more efficacious than groups 2 and 3. The classification was shown to predict out-of-sample clinical effects of individual drugs. CONCLUSIONS: A receptor affinity-based grouping not only reflects compound pharmacology but also detects meaningful clinical differences. This approach has the potential to benefit both patients and researchers by guiding treatment and informing drug development.

CAPTURE ALS: the comprehensive analysis platform to understand, remedy and eliminate ALS.

The absence of disease modifying treatments for amyotrophic lateral sclerosis (ALS) is in large part a consequence of its complexity and heterogeneity. Deep clinical and biological phenotyping of people living with ALS would assist in the development of effective treatments and target specific biomarkers to monitor disease progression and inform on treatment efficacy. The objective of this paper is to present the Comprehensive Analysis Platform To Understand Remedy and Eliminate ALS (CAPTURE ALS), an open and translational platform for the scientific community currently in development. CAPTURE ALS is a Canadian-based platform designed to include participants' voices in its development and through execution. Standardized methods will be used to longitudinally characterize ALS patients and healthy controls through deep clinical phenotyping, neuroimaging, neurocognitive and speech assessments, genotyping and multisource biospecimen collection. This effort plugs into complementary Canadian and international initiatives to share common resources. Here, we describe in detail the infrastructure, operating procedures, and long-term vision of CAPTURE ALS to facilitate and accelerate translational ALS research in Canada and beyond.

Instructional review of key factors to achieve successful outcomes when using low-intensity pulsed ultrasound in fracture repair.

Low-intensity pulsed ultrasound (LIPUS) treatment of fractures has been available to the orthopaedic community for nearly three decades; however, it is still considered an experimental treatment by some clinicians, even though there is a wealth of clinical data. Based on the evaluation of clinical trial data, we have established key criteria which can lead to LIPUS success and avoid failure. These are fracture gap size and stability, accurate transducer placement and minimum treatment number. However, from a clinician's view, the correct attitude to treatment must be observed, and this has also been discussed. It is hoped, armed with this new evaluation of the clinical data, that clinicians can treat patients with LIPUS more effectively, resulting in fewer failures of treatment.

Selective border permeability: Governing complex environmental issues through and beyond COVID-19.

COVID-19 has changed the permeability of borders in transboundary environmental governance regimes. While borders have always been selectively permeable, the pandemic has reconfigured the nature of cross-border flows of people, natural resources, finances and technologies. This has altered the availability of spaces for enacting sustainability initiatives within and between countries. In Southeast Asia, national governments and businesses seeking to expedite economic recovery from the pandemic-induced recession have selectively re-opened borders by accelerating production and revitalizing agro-export growth. Widening regional inequities have also contributed to increased cross-border flows of illicit commodities, such as trafficked wildlife. At the same time, border restrictions under the exigencies of controlling the pandemic have led to a rolling back and scaling down of transboundary environmental agreements, regulations and programs, with important implications for environmental democracy, socio-ecological justice and sustainability. Drawing on evidence from Southeast Asia, the article assesses the policy challenges and opportunities posed by the shifting permeability of borders for organising and operationalising environmental activities at different scales of transboundary governance.

Assessment of emergency department staff awareness, access and utilisation of advance care directives and goals of care: A cross-sectional survey.

BACKGROUND: Emergency department staff awareness, access and implementation of advance care directives and goals of care documents and the related patient consent processes are important but not well understood. METHODS: A cross-sectional survey using purposive sampling was undertaken at a tertiary hospital's Emergency Department from 15th March to 26th April 2021. Participants were recruited through online platforms. Pre-validated questionnaires were distributed by email or as QR codes on bulletin boards. Data collected included staff: demographics, knowledge, access and implementation of advance care directives and goals of care documentation. RESULTS: One hundred thirty-four (28%) of 476 targeted participants responded with nursing forming largest group. Results showed that previous attendance of advance care planning education was low at 20%. Familiarity with advance care directive documentations was only 19% while with goals of care document was average. 61 (48%) respondents reported ease of accessing electronic documents and 21 (19%) reported feeling very comfortable discussing and setting goals of care with patients (p = <0.01). CONCLUSIONS: Staff awareness of advance care directive was poor, while awareness of goals of care was average. There was no association between advance care directives awareness and staff age group, gender, length of: - professional practice, practice at the study site.

Regular medication use by active scuba divers with a declared comorbid medical condition and victims of scuba and snorkelling-related fatalities.

INTRODUCTION: The aim of this study was to describe the nature of regular medications taken by active comorbid scuba divers (having a declared medical comorbidity) and scuba divers and snorkellers who died following a diving incident. METHODS: We undertook a retrospective, observational study from July to October, 2020. Data on 268 active comorbid divers were obtained through a 2013 survey of Divers Alert Network Asia-Pacific members. Data on 126 deceased scuba divers and 175 deceased snorkellers were obtained predominantly from 2001-2013 reports to Australian State Coronial Services. RESULTS: The active comorbid divers were significantly older, less likely to be male, and more likely to be taking one or more medications than the two deceased subject groups (P < 0.001). Cardiovascular, endocrine and psychotropic medications accounted for 53.4%, 9.9% and 6.4% of all medications taken, respectively. Almost one tenth of the deceased divers took at least one psychotropic medication, a proportion significantly greater than the other groups (P = 0.01). CONCLUSIONS: Medication use among active comorbid divers is common which likely reflects their declared medical condition. Nevertheless, they appear to be diving relatively safely, often with conditions once thought to be absolute contradictions to scuba diving. The deceased divers took significantly more psychotropic medications. It is possible that their underlying psychological/psychiatric conditions rendered them more at risk of a diving incident. Increased vigilance for psychological conditions may need to be considered during diving medical examinations.

Vitamin D in the time of the coronavirus (COVID-19) pandemic - a clinical review from a public health and public mental health perspective.

Individuals with serious mental disorders (SMD) may have a higher risk of vitamin D (VIT-D) deficiency. They also experience higher mortality because of coronavirus disease 2019 (COVID-19) infection. Therefore, we have conducted a comprehensive review to examine the significance of VIT-D for public health and public mental health during the ongoing COVID-19 pandemic. This review had three specific aims, from a global perspective to (a) create a profile of VIT-D and review the epidemiology of VIT-D deficiency, (b) explore VIT-D deficiency as risk factor for SMD and COVID-19 infections and (c) examine the effectiveness of VIT-D supplementation for both conditions. We found that, in terms of SMD, the evidence from laboratory and observational studies points towards some association between VIT-D deficiency and depression or schizophrenia. Mendelian randomisation studies, however, suggest no, or reverse, causality. The evidence from intervention studies is conflicting. Concerning COVID-19 infection, on proof of principle, VIT-D could provide a plausible defence against the infection itself and against an adverse clinical course. But data from observational studies and the first preliminary intervention studies remain conflicting, with stronger evidence that VIT-D may mitigate the clinical course of COVID-19 infection rather than the risk of infection in the first place. From a public health and public mental health point of view, based on the currently limited knowledge, for individuals with SMD, the benefits of VIT-D optimisation through supplementation seem to outweigh the risks. VIT-D supplementation, however, should not substitute for vaccination or medical care for COVID-19 infection.

The CANBACK trial: a randomised, controlled clinical trial of oral cannabidiol for people presenting to the emergency department with acute low back pain.

OBJECTIVE: To assess the analgesic efficacy and safety of single-dose oral cannabidiol (CBD) as an adjunct to standard care for patients presenting to an emergency department with acute low back pain. DESIGN: Randomised, double blinded, placebo-controlled clinical trial. SETTING: The tertiary emergency department of Austin Hospital, Melbourne. PARTICIPANTS: Patients who presented with acute, non-traumatic low back pain between 21 May 2018 and 13 June 2019. INTERVENTION: One hundred eligible patients were randomised to receiving 400 mg CBD or placebo in addition to standard emergency department analgesic medication. MAIN OUTCOME MEASURES: Pain score two hours after administration of study agent, on a verbal numerical pain scale (range, 0-10). Secondary outcomes were length of stay, need for rescue analgesia, and adverse events. RESULTS: The median age of the 100 participants was 47 years (IQR, 34-60 years); 44 were women. Mean pain scores at two hours were similar for the CBD (6.2 points; 95% CI, 5.5-6.9 points) and placebo groups (5.8 points; 95% CI, 5.1-6.6 points; absolute difference, -0.3 points; 95% CI, -1.3 to 0.6 points). The median length of stay was 9.0 hours (IQR, 7.4-12 hours) for the CBD group and 8.5 hours (IQR, 6.5-21 hours) for the placebo group. Oxycodone use during the four hours preceding and the four hours after receiving CBD or placebo was similar for the two groups, as were reported side effects. CONCLUSION: CBD was not superior to placebo as an adjunct medication for relieving acute non-traumatic low back pain in the emergency department. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12618000487213 (prospective).

A prospective, randomized, double-blind trial of intravenous chlorpromazine versus intravenous prochlorperazine for the treatment of acute migraine in adults presenting to the emergency department.

OBJECTIVE: To compare the efficacy of intravenous chlorpromazine versus intravenous prochlorperazine for the treatment of acute migraine in adults presenting to the emergency department (ED). BACKGROUND: Migraine is a common, incapacitating neurological condition. Although chlorpromazine and prochlorperazine are known to be safe, efficacious treatments for migraine, they have never been directly compared. DESIGN: We performed a prospective, randomized, double-blind clinical trial at a tertiary hospital in Melbourne, Australia. Adults aged 18-65 years, who presented with migraine, were eligible for recruitment. Sixty-six patients were randomized to either chlorpromazine 12.5 mg or prochlorperazine 12.5 mg, both infused in 500 ml of sodium chloride 0.9% over 30 min. Headache severity score, nausea severity score, and the presence of photophobia and phonophobia were assessed at 0, 30, 60, and 120 min. Adverse effects and the need for rescue therapy were recorded. The primary outcome was a reduction in headache severity score from baseline at 60 min post-commencement of the study medicine infusion. RESULTS: Sixty-five patients were included in the analysis. There was a median reduction in headache severity score at 60 min of 3.0 (interquartile range 1.0-4.0) in the chlorpromazine arm versus 2.0 (1.0-4.0) in the prochlorperazine arm (median difference -0.5 (95% confidence interval, -1.9 to 0.9)). We saw no evidence of a difference in secondary outcomes at 30, 60, or 120 min. Side effects were reported in 16/32 (50%) patients in the chlorpromazine group versus 7/33 (21%) in the prochlorperazine group (p = 0.020). Rescue therapy was required in 7/32 (22%) patients in the chlorpromazine group versus 12/33 (36%) in the prochlorperazine group (p = 0.277). CONCLUSIONS: Both chlorpromazine and prochlorperazine are efficacious treatments for acute migraine in adult patients presenting to the ED. This trial found no evidence of superiority of either agent over the other. Caution should be used when prescribing these medicines in the borderline hypotensive patient; in that circumstance, prochlorperazine should be preferentially used.

Intramuscular midazolam, olanzapine, or haloperidol for the management of acute agitation: A multi-centre, double-blind, randomised clinical trial.

BACKGROUND: The safety and effectiveness of intramuscular olanzapine or haloperidol compared to midazolam as the initial pharmacological treatment for acute agitation in emergency departments (EDs) has not been evaluated. METHODS: A pragmatic, randomised, double-blind, active-controlled trial was conducted from December 2014 to September 2019, in six Hong Kong EDs. Patients (aged 18-75 years) with undifferentiated acute agitation requiring parenteral sedation were randomised to 5 mg intramuscular midazolam (n = 56), olanzapine (n = 54), or haloperidol (n = 57). Primary outcomes were time to adequate sedation and proportion of patients who achieved adequate sedation at each follow-up interval. Sedation levels were measured on a 6-level validated scale (ClinicalTrials.gov Identifier: NCT02380118). FINDINGS: Of 206 patients randomised, 167 (mean age, 42 years; 98 [58·7%] male) were analysed. Median time to sedation for IM midazolam, olanzapine, and haloperidol was 8·5 (IQR 8·0), 11·5 (IQR 30·0), and 23·0 (IQR 21·0) min, respectively. At 60 min, similar proportions of patients were adequately sedated (98%, 87%, and 97%). There were statistically significant differences for time to sedation with midazolam compared to olanzapine (p = 0·03) and haloperidol (p = 0·002). Adverse event rates were similar across the three arms. Dystonia (n = 1) and cardiac arrest (n = 1) were reported in the haloperidol group. INTERPRETATION: Midazolam resulted in faster sedation in patients with undifferentiated agitation in the emergency setting compared to olanzapine and haloperidol. Midazolam and olanzapine are preferred over haloperidol's slower time to sedation and potential for cardiovascular and extrapyramidal side effects. FUNDING: Research Grants Council, Hong Kong.

An evaluation of the variation and underuse of clozapine in the United Kingdom.

BACKGROUND: Clozapine is the only licensed treatment for treatment refractory schizophrenia. Despite this, it remains grossly underused relative to the prevalence of refractory schizophrenia. The extent of underuse and the degree of regional variation in prescribing in the United Kingdom is unknown. It is also unclear, how the UK compares with other European countries in rates of clozapine prescribing. METHODS: We obtained data relating to all clozapine prescribing in the UK from the relevant clozapine registries. We examined regional variation in clozapine use across England, corrected for the known prevalence of severe mental illness (SMI). We also compared the UK rate of clozapine use per 100,000 population to that described in other European countries. FINDINGS: There is substantial variation in clozapine prescribing across different regions of England and only about a third of potentially eligible patients were prescribed the drug in the UK. Clozapine prescribing rate in the UK was lower than in several European countries. INTERPRETATION: There is clear regional inequity in access to the most effective treatment in refractory schizophrenia in England. Strategies to increase clozapine use, by overcoming both real and perceived barriers, are urgently necessary to reduce treatment inequity for patients with refractory schizophrenia.

Surgical Exposure of the Distal Fibula to Protect the Peroneus Brevis Muscle Vascular Pedicle.

Ankle fractures are a common presentation to orthopaedic surgeons, with the lateral malleolus involved in 86% of cases. A soft tissue injury can be a concomitant feature of these injuries as a result of the primary injury or following secondary wound breakdown. The peroneus brevis muscle flap provides a reliable and robust option to cover the distal third of the lower limb. With an understanding of the anatomy and cautious dissection during periosteal elevation, the perforating vessels supplying the peroneus brevis can be preserved ensuring that a valuable reconstructive option is available. HOW TO CITE THIS ARTICLE: Irvine E, Cochrane E, Harwood P, et al. Surgical Exposure of the Distal Fibula to Protect the Peroneus Brevis Muscle Vascular Pedicle. Strategies Trauma Limb Reconstr 2021;16(3):176-178.

The Effect of the Consent Process on Patient Satisfaction With Pain Management: A Randomized Controlled Trial.

STUDY OBJECTIVE: We aim to determine whether the timing and context of informed consent affects the subjective outcome of patient satisfaction with pain management. METHODS: We conducted a randomized controlled trial in a single emergency department (ED). Patients aged 18 years or older with a triage pain score of greater than or equal to 4 provided consent to participate in a pain management study. They were randomized to consent in the ED or at follow-up. All patients were followed up at 48 hours post-ED discharge. Patients who consented at follow-up were unaware of the study until cold called. The primary outcome was patient satisfaction with pain management. Secondary analyses examined effects on follow-up and participation rates. Variables associated with patients' being very satisfied were determined with multivariate logistic regression. RESULTS: Outcome data were obtained on 655 of 825 patients enrolled (79.4%). Patients who provided consent at follow-up were less likely to be very satisfied compared with those who consented in the ED (difference in proportions 11.5%; 95% confidence interval 3.5 to 19.4). Follow-up and participation rates did not differ between the groups. Patients who received pain advice and adequate analgesia (both as defined in this study) were more likely to be very satisfied (odds ratio 5.18, 95% confidence interval 2.82 to 9.52; and odds ratio 1.54, 95% confidence interval 1.07 to 2.22, respectively). CONCLUSION: The timing and context of informed consent significantly affect the subjective outcome of patient satisfaction, and this should be considered during study design. Clinicians should strive to provide pain advice and adequate analgesia to maximize their patients' satisfaction.

Positive views on antipsychotic long-acting injections: results of a survey of community patients prescribed antipsychotics.

BACKGROUND: We aimed to assess patients' views about antipsychotic long-acting injections (LAIs). METHODS: We interviewed patients prescribed an antipsychotic (oral or LAI) in our community teams. In a subanalysis, responses were analysed for differences between patients currently receiving an LAI and those prescribed only oral medication. RESULTS: In total, 226 patients (57%) completed the study questionnaire. The majority agreed that LAIs ensured delivery of the right amount of medication and protection against hospital admissions (57% and 60%, respectively). A minority of participants were more concerned than not about the use of a needle (46%), pain from injection (48%) and the need to travel to receive the injection (34%). A majority expressed a preference for injection site (deltoid or gluteal) (65%) and clinic location (69%). A higher proportion of patients currently receiving an LAI compared with those prescribed oral medication thought an LAI was beneficial because this formulation obviated the need to: swallow tablets (63% versus 41%; p = 0.0013), remember to take tablets daily (75% versus 51%; p = 0.0004), remember tablets when away from home (72% versus 49%; p = 0008). Current LAI users were more likely than those on oral treatment to agree that LAIs keep patients out of hospital (76% versus 44%; p = 0.0001) and that the injection ensured delivery of the right amount of medication (71% versus 44%; p = 0.0002). Women were more likely than men to prefer administration by a clinician of the same gender (34% versus 12%; p = 0.0001). CONCLUSIONS: In our study, a greater proportion of patients prescribed an LAI regarded LAIs as beneficial compared with those on oral medication.

Joint BAP NAPICU evidence-based consensus guidelines for the clinical management of acute disturbance: De-escalation and rapid tranquillisation.

The British Association for Psychopharmacology and the National Association of Psychiatric Intensive Care and Low Secure Units developed this joint evidence-based consensus guideline for the clinical management of acute disturbance. It includes recommendations for clinical practice and an algorithm to guide treatment by healthcare professionals with various options outlined according to their route of administration and category of evidence. Fundamental overarching principles are included and highlight the importance of treating the underlying disorder. There is a focus on three key interventions: de-escalation, pharmacological interventions pre-rapid tranquillisation and rapid tranquillisation (intramuscular and intravenous). Most of the evidence reviewed relates to emergency psychiatric care or acute psychiatric adult inpatient care, although we also sought evidence relevant to other common clinical settings including the general acute hospital and forensic psychiatry. We conclude that the variety of options available for the management of acute disturbance goes beyond the standard choices of lorazepam, haloperidol and promethazine and includes oral-inhaled loxapine, buccal midazolam, as well as a number of oral antipsychotics in addition to parenteral options of intramuscular aripiprazole, intramuscular droperidol and intramuscular olanzapine. Intravenous options, for settings where resuscitation equipment and trained staff are available to manage medical emergencies, are also included.

Obstructive Sleep Apnea is an Independent Risk Factor for Hospital Readmission.

STUDY OBJECTIVES: Hospital readmissions are an important metric of quality and safety. This study seeks to characterize the relationship between readmissions and obstructive sleep apnea (OSA). A better understanding of this relationship could be utilized to develop preventative measures and reduce readmission rates. METHODS: A retrospective review of patients discharged over a 24-month period to a Department of Defense hospital was conducted. Medical records review provided demographic data, presence of OSA and comorbid diseases, and whether readmission occurred within 30 days of discharge. Statistical analysis assessed risk factors for readmission, and multivariate analysis was performed. Next, 125 readmitted patients with OSA were randomly selected for detailed chart review and compared to a matched cohort that was not readmitted. RESULTS: Of 22,261 unique patients discharged, 1,899 (8.5%) were readmitted. Patients with OSA had a readmission rate of 11.4% versus 7.6% for patients without OSA (P < .00001). Multivariable analysis revealed an odds ratio of 1.46 for readmission in patients with OSA (P < .0001). For the detailed chart review of 250 patients, length of hospital stay differed for the readmitted and non-readmitted groups (5.1 versus 3.6 days; P = .007). Apnea-hypopnea index (24.1 versus 27.2 events/h; P = .48) was similar between the groups. Also, inpatient (27.2% versus 26.4%) and outpatient (38.4% versus 37.6%) positive airway pressure (PAP) treatment rates were not different. CONCLUSIONS: This study found OSA to be an independent risk factor for readmission within 30 days of discharge. PAP therapy appears to be underutilized in patients with known OSA. Additional studies are needed to define the relationship between OSA, PAP adherence, and hospital readmission.

Long-term follow-up of clozapine prescribing.

OBJECTIVE: Clozapine is uniquely effective for treatment-resistant schizophrenia, and so treatment continuation is essential. We aimed to identify factors associated with an increased likelihood of clozapine discontinuation in a cohort of patients in South East London. METHODS: We gathered demographic and treatment information such as duration of illness and antipsychotic treatment history. t-tests, chi-square tests and binary logistic regression were used to compare patients who continued and discontinued clozapine during the study and to identify predictor variables for discontinuation. RESULTS: Out of the study population of 133 patients, 48 discontinued clozapine at least once during the study period. The majority of these (75%) stopped treatment within the first 4 years of clozapine therapy. Age, ethnicity, diagnosis and antipsychotic treatment history were not predictive of the risk of clozapine discontinuation. However, male patients were more likely to stop taking clozapine (χ2 = 6.81, p = 0.009). The odds of discontinuing clozapine were 2.15 times higher for male patients. The most common reason for discontinuation was patient refusal of treatment. CONCLUSION: We found that patients who discontinue clozapine are more likely to be male, but no other demographic variable was found to predict treatment cessation. Discontinuation usually occurred due to patient refusal of treatment.