Differences in heroin overdose deaths in Australia by age, 2020-2022: Disease and estimated survival times.

Background: The age of people who use illicit opioids has increased, with a clinical picture of accelerated ageing. The study aimed to determine, stratified by age: 1. The circumstances and characteristics of heroin-related toxicity deaths in Australia, 2020-2022; 2. The toxicological profile and autopsy findings; 3. The proportion of cases in which blood 6-acetyl morphine (6AM) was detected, as a measure of survival time. Methods: Retrospective study of 610 cases of fatal heroin-related drug toxicity in Australia, 2020-2022. Cases were stratified as: <30 years, 30-39 years, 40-49 years, ≥50 years. Results: Compared to the youngest group, those aged ≥50 years were more likely to have a history of chronic pain (12.4 v 3.3 %), to have their death attributed to combined drug toxicity/disease (20.1 v 3.3 %), and to have evidence of a sudden collapse (21.3 v 11.1 %). There were no differences in free morphine concentrations or glucuronide concentrations. Compared to the youngest group, however, the two older groups were significantly more likely to have 6AM present in blood, a proxy measure of a shorter survival time (52.0, 55.2 v 34.5 %). Compared to the youngest group, cases aged ≥50 years were more likely to be diagnosed with cardiomegaly (44.0 v 16.7 %), coronary artery disease (46.0 v 15.0 %), emphysema (35.0 v 5.1 %), hepatic steatosis (15.4 v 3.4 %), hepatic fibrosis (17.6 v 3.4 %), and cirrhosis (19.8 v 0.0 %). Conclusions: Older cases of heroin overdose had more extensive heart, lung, and liver disease, and appeared more likely to have shorter survival times.

Characteristics, toxicology and major organ pathology of deaths due to acute alcohol toxicity in Australia, 2011-2022.

INTRODUCTION: Acute alcohol toxicity is a significant component of alcohol-related mortality. The study aimed to: (i) determine the circumstances of death and characteristics of fatal alcohol toxicity cases, 2011-2022; (ii) determine their toxicological profile and major autopsy findings; and (iii) determine trends in population mortality rates. METHODS: Retrospective study of acute alcohol toxicity deaths in Australia, 2011-2022, retrieved from the National Coronial Information System. RESULTS: A total of 891 cases were identified, with a mean age of 49.2 years, 71.0% being male. Alcohol use problems were noted in 71.3%. In 57.5% death was attributed solely to acute alcohol toxicity, and combined acute alcohol toxicity/disease in 42.5%. There was evidence of sudden collapse in 24.9% of cases. The mean BAC was 0.331 g/100 mL (range 0.107-0.936), and spirits were the most commonly reported beverages (35.8%). Cases of combined toxicity/disease had significantly lower BACs than those attributed solely to alcohol toxicity (0.296 vs. 0.358 g/100 mL). Cardiomegaly was diagnosed in 32.5%, and severe coronary artery disease in 22.1%. Aspiration of vomitus was noted in 18.0%, and chronic obstructive pulmonary disease in 19.6%. Severe liver steatosis was present in 33.4% and 13.6% had cirrhosis. There was an average annual percentage increase in deaths of 7.90. DISCUSSION AND CONCLUSIONS: The 'typical' case was a long-standing, heavy spirits drinker. BACs showed enormous variation and no arbitrary concentration may be deemed lethal. Clinically significant disease was associated with death at a lower BAC and people with such disease may be at increased risk of alcohol poisoning.

A descriptive coronial study of heroin toxicity deaths in Australia, 2020-2022: Characteristics, toxicology and survival times.

BACKGROUND AND AIMS: Mortality rates among people who use heroin are estimated to be 15 times that of the general population. The study aimed to determine (1) the case characteristics and circumstances of death of heroin-related toxicity deaths in Australia, 2020-2022; (2) their toxicological profile and major autopsy findings; (3) the proportion of cases in which blood 6-acetyl morphine (6AM) was detected, as a proxy measure of survival times; and (4) compare 6AM positive and negative cases on toxicology, circumstances of death and acute clinical presentation. DESIGN: Retrospective study of heroin toxicity deaths in Australia, 2020-2022, retrieved from the National Coronial Information System. SETTING: This study was conducted Australia-wide. CASES: There were 610 cases of fatal heroin-related drug toxicity. MEASUREMENTS: Information was collected on characteristics, manner of death, toxicology and autopsy results. FINDINGS: The mean age was 42.6 years (range 18-73 years), 80.5% were male and 7.5% were enrolled in a drug treatment programme. The circumstances of death were as follows: unintentional drug toxicity (86.2%), combined unintentional drug toxicity/disease (11.3%) and intentional drug toxicity (2.5%). The median free morphine concentration was 0.17 mg/L (range 0.00-4.20 mg/L). Psychoactive drugs other than heroin were present in 95.2% (Confidence Interval 93.1%-96.8%), most commonly hypnosedatives (62.3%, 58.2%-66.4%) and psychostimulants (44.8%, 40.7%-49.1%). Major autopsy findings of clinical significance included acute bronchopneumonia (14.8%, 11.3%-18.8%), emphysema (16.9%, 13.2%-21.1%), cardiomegaly (30.1%, 12.7%-28.2%), coronary artery disease (27.4%, 23.0%-32.3%), coronary replacement fibrosis (13.4%, 10.1%-17.3%), hepatic cirrhosis (8.8%, 6.6%-12.2%) and renal fibrosis (10.3%, 7.3%-14.0%). In 47.0% (42.3%-51.2%), 6AM was present in blood. CONCLUSIONS: The 'typical' heroin overdose case in Australia from 2020 to 2022 was a male who injected heroin, aged in the 40s, not enrolled in a treatment programme and had used multiple drugs. In over half of cases, there had been a sufficient survival time for 6-acetyl morphine to have been metabolised, which may indicate times in excess of 20-30 min.

Adjunctive canakinumab reduces peripheral inflammation markers and improves positive symptoms in people with schizophrenia and inflammation: A randomized control trial.

BACKGROUND: Clinical trials of anti-inflammatories in schizophrenia do not show clear and replicable benefits, possibly because patients were not recruited based on elevated inflammation status. Interleukin 1-beta (IL-1ß) mRNA and protein levels are increased in serum, plasma, cerebrospinal fluid, and brain of some chronically ill patients with schizophrenia, first episode psychosis, and clinical high-risk individuals. Canakinumab, an approved anti-IL-1ß monoclonal antibody, interferes with the bioactivity of IL-1ß and interrupts downstream signaling. However, the extent to which canakinumab reduces peripheral inflammation markers, such as, high sensitivity C-reactive protein (hsCRP) and symptom severity in schizophrenia patients with inflammation is unknown. TRIAL DESIGN: We conducted a randomized, placebo-controlled, double-blind, parallel groups, 8-week trial of canakinumab in chronically ill patients with schizophrenia who had elevated peripheral inflammation. METHODS: Twenty-seven patients with schizophrenia or schizoaffective disorder and elevated peripheral inflammation markers (IL-1ß, IL-6, hsCRP and/or neutrophil to lymphocyte ratio: NLR) were randomized to a one-time, subcutaneous injection of canakinumab (150 mg) or placebo (normal saline) as an adjunctive antipsychotic treatment. Peripheral blood hsCRP, NLR, IL-1ß, IL-6, IL-8 levels were measured at baseline (pre injection) and at 1-, 4- and 8-weeks post injection. Symptom severity was assessed at baseline and 4- and 8-weeks post injection. RESULTS: Canakinumab significantly reduced peripheral hsCRP over time, F(3, 75) = 5.16, p = 0.003. Significant hsCRP reductions relative to baseline were detected only in the canakinumab group at weeks 1, 4 and 8 (p's = 0.0003, 0.000002, and 0.004, respectively). There were no significant hsCRP changes in the placebo group. Positive symptom severity scores were significantly reduced at week 8 (p = 0.02) in the canakinumab group and week 4 (p = 0.02) in the placebo group. The change in CRP between week 8 and baseline (b = 1.9, p = 0.0002) and between week 4 and baseline (b = 6.0, p = 0.001) were highly significant predictors of week 8 change in PANSS Positive Symptom severity scores. There were no significant changes in negative symptoms, general psychopathology or cognition in either group. Canakinumab was well tolerated and only 7 % discontinued. CONCLUSIONS: Canakinumab quickly reduces peripheral hsCRP serum levels in patients with schizophrenia and inflammation; after 8 weeks of canakinumab treatment, the reductions in hsCRP are related to reduced positive symptom severity. Future studies should consider increased doses or longer-term treatment to confirm the potential benefits of adjunctive canakinumab in schizophrenia. Australian and New Zealand Clinical Trials Registry number: ACTRN12615000635561.

Parental bonding style and illness severity in a longitudinal study of individuals with first episode psychosis.

A parenting style with high amounts of control combined with low caring or nurturing behaviour has been reported in association with mental disorders including schizophrenia. However, the association of parenting style with illness severity in individuals with schizophrenia has never been evaluated retrospectively or over a longitudinal time course. In a subset (n = 84) of the participants included in the AESOP (Aetiology and Ethnicity in Schizophrenia and Other Psychoses)-10 study, we evaluated participants' perceptions of their own parents' bonding style at the time of their first episode of psychosis using the parental bonding instrument (PBI). We then examined the association between different bonding styles, illness course and severity, and global functioning over a 10-year follow-up. Participants who perceived that their fathers had a more caring and less controlling parenting style showed better functioning at follow-up. However, in contrast to previous research, participants who reported having been subject to uncaring and controlling parenting styles were not found to have a notably worse course of illness or symptom severity over the follow-up period. These results indicate that more optimal parental bonding styles may be associated with better overall functioning in individuals with psychosis but not with other measures of illness outcome.

The tertiary service for psychosis: Holistic recommendations for people with complex psychosis.

OBJECTIVE: To describe (i) the clinical characteristics of individuals referred to the Tertiary Referral Service for Psychosis (TRSP) and (ii) the recommendations TRSP made for future treatment across psychopharmacological and other intervention domains. METHOD: Retrospective audit of clinical data collected during the assessment process of individuals who accessed TRSP between 02/06/2020 and 31/12/2022. Categories of recommendations made following collaborative care planning comprised psychopharmacological, neuropsychological, psychological, psychosocial, physical health, substance misuse and other domains. RESULTS: Eighty-two individuals were included, with diagnoses most commonly of schizophrenia (54.9%) and schizoaffective disorder (30.5%). The median PANSS score was 88.0 (73-100). Social occupational functioning was very poor (SOFAS M = 37.0, SD = 15.1). Cognitive functioning was poor (RBANS: M = 74.6; SD: 15.0). 67.1% had physical health comorbidities, with high prevalence of smoking (52.4%) and substance misuse (25.6%). Psychopharmacological recommendations (made for 81.7%) included clozapine trial (25.6%), clozapine dose change/augmentation (22.0%) and rationalisation of polypharmacy (12.2%). Neuropsychological (73.2%), psychological (39.0%) and psychosocial (85.4%) recommendations included access to cognitive remediation, psychological therapy and disability support. Physical health and substance misuse interventions were recommended for 91.5% and 20.7%, respectively. CONCLUSIONS: Individuals referred to the TRSP had marked clinical and functional impairments. Holistic collaborative care planning complemented psychopharmacological interventions with psychological, psychosocial and physical healthcare recommendations.

Cognitive remediation therapy - implementation and translation into clinical practice in rural and metropolitan New South Wales mental health services.

OBJECTIVE: Cognitive Remediation Therapy (CRT) is an effective intervention in managing the significant cognitive deficits experienced by those living with psychosis. Given its strong evidence base CRT is recommended in Australian and international guidelines for rehabilitation of people with psychosis, however, access to CRT remains limited. In this commentary, we describe recent efforts to implement CRT programs within NSW mental health services. Development of CRT delivery has been successfully achieved in both rural and metropolitan settings, utilising both face-to-face and telehealth methods. CONCLUSIONS: The delivery of CRT in public mental health services is feasible and adaptable to diverse settings. We strongly advocate for sustainable implementation of CRT into routine clinical practice. This will require policy and practice change to enable resources for CRT training and delivery to become embedded in the roles of the clinical workforce.

Utilising the Implementation of Integrated Care to Develop a Pragmatic Framework for the Sustained Uptake of Service Innovations (SUSI).

The provision of integrated care (IC) across alcohol and other drug (AOD) and mental health (MH) services represents the best practice, yet the consistent delivery of IC in routine practice rarely occurs. Our hypothesis is that there is no practical or feasible systems-change approach to guide staff, researchers, or consumers through the complex transition that is required for the sustained uptake of IC across diverse clinical settings. To address this gap, we combined clinical and consumer expertise with the best available research evidence to develop a framework to drive the uptake of IC. The goal was to develop a process that is both standardised by the best available evidence and can be tailored to the specific characteristics of different health services. The result is the framework for Sustained Uptake of Service Innovation (SUSI), which comprises six core components that are applied in a specified sequence and a range of flexible activities that staff can use to deliver the core components according to their circumstances and preferences. The SUSI is evidence-based and practical, and further testing is currently underway to ensure it is feasible to implement in different AOD and MH services.

Characteristics and circumstances of volatile solvent misuse-related death in Australia, 2000-2021.

INTRODUCTION: Volatile solvent misuse-related death is associated with neuropsychiatric, cardiovascular, respiratory and renal pathology, as well as sudden death. The study aimed to determine: (1) the circumstances of death and case characteristics of volatile solvent misuse-related death in Australia, 2000-2021; (2) the toxicological profile of cases; and (3) the major autopsy findings. METHODS: Retrospective study of volatile solvent misuse-related death in Australia, 2000-2021 retrieved from the National Coronial Information System. FINDINGS: One hundred and sixty-four cases were identified, 79.9% male, mean age 26.5 years (8.5% aged 40 years or older). Circumstances of death were unintentional toxicity (61.0%), unintentional asphyxia (20.1%), intentional self-harm (12.2%) and traumatic accident (6.7%). The most commonly reported acute presentation prior to death was sudden collapse (22 of 47 witnessed events). The most frequently used solvents at the fatal incident were gas fuels (35.4%), gasoline (petrol) (19.5%) adhesives/paints (19.5%), aerosol propellants (12.8%), and volatile anaesthetics (12.8%). The most commonly detected volatile substances were butane (40.7%), toluene (29.6%), and propane (25.9%). Cannabis was present in 27.6% and alcohol in 24.6%. The prevalence of acute pneumonia amongst autopsied cases was low (5.8%) which, together with reports of sudden collapse, suggests that in many cases, death was extremely rapid. There were low levels of major organ pathology. CONCLUSIONS: While the average age of volatile solvent misuse-related death was in the mid-twenties, a substantial proportion occurred amongst people aged 40 years or older. Reflecting availability, gas fuels predominated. In many cases, death appeared to have been rapid.

Overdose and suicide are different phenomena among opioid users that require different clinical management.

Given the high rates of mental health comorbidity among opioid users, and increasing rates of opioid prescription for chronic pain, psychiatrists and mental health clinicians are likely to treat patients who are dependent on opioids. Among such patients, many will have histories of opioid overdose or suicide attempts. It is tempting to assume that these are related behaviours and that 'accidental' overdoses are actually suicide attempts. We provide evidence here to demonstrate that while some overdoses are intentional, most are not. More than half of deaths among opioid users are due to unintentional overdose. Suicides constitute a minority: less than 10% of heroin user deaths are estimated to be due to suicide, as are 20-30% of prescribed opioid fatalities. Moreover, suicide attempts are more commonly made using means other than opioids. Overdose and suicide among opioid dependent patients are two distinct phenomena, associated with different risk factors, that need to be separately assessed and their respective risk managed.

A systematic review of factors associated with sustained smoking abstinence in people experiencing severe mental illness following participation in a smoking intervention.

OBJECTIVE: People experiencing severe mental illness report higher rates of tobacco smoking than the general population, while rates of quitting and sustaining abstinence are considerably lower. This systematic review aimed to identify factors associated with sustained abstinence in people experiencing severe mental illness following a smoking intervention. METHOD: Searches were conducted in PubMed, PsycInfo, Scopus, Embase, Emcare, CINAHL and Cochrane Library from the inception of the e-databases until June 2022. Selection criteria included randomised and non-randomised studies of smoking cessation interventions in which most of the participants were experiencing severe mental illness, and reported a follow-up of 3 months or longer. From an initial 1498 unique retrieved records, 26 references were included detailing 17 smoking cessation intervention studies and 3 relapse prevention intervention studies. Risk of bias was assessed using the RoB2 tool for randomised study designs and the ROBINS-I tool for non-randomised designs. RESULTS: Participation in smoking interventions was associated with higher odds of abstinence in the medium-term, but not long-term follow-ups. There was insufficient evidence that any other factors impact sustained abstinence. Most studies were considered to have some risk of bias, largely due to insufficient availability of analysis plans. CONCLUSION: Despite an abundance of studies investigating smoking cessation in smokers experiencing severe mental illness, there is limited knowledge on the factors associated with staying quit. The inclusion of people experiencing severe mental illness in large-scale randomised control trials, in which predictors of sustained abstinence are measured in the medium and long term are needed to address this important question.

Characteristics and circumstances of cocaine-related completed suicide in Australia, 2000-2021.

BACKGROUND: There has been a substantial global increase in cocaine use and associated harms. The current study aimed to: 1. Determine the case characteristics and circumstances of death of cocaine-related suicide in Australia 2000-2021; and 2. Determine the toxicological profiles of cases. METHODS: Retrospective study of cocaine-related death in Australia, 2000-2021, retrieved from the National Coronial Information System (NCIS). Suicide intent was based upon the NCIS code for "Intentional Self-harm", derived from case circumstances and coroners' conclusions. Sex comparisons were made for all major variables. RESULTS: A total of 157 cases were identified, 82.2% male, 79.5% employed, with a mean age of 32.3 years. Concerns for mental health were documented in 65.6%, a previous suicide attempt in 21.0%, a history of substance use treatment and/or negative consequences of substance use in 45.9% and injecting drug use in 14.6%. Manner of death amongst both sexes was predominantly by physical means (82.8%). Written intent was documented in 29.3%. Intense agitation prior to the incident was noted in 28.0% and conflict in 24.8%. The median blood cocaine concentration was 0.060 mg/L (range 0.007-5.500). Other drugs were present in 95.5%, most commonly alcohol (63.1%) with a median concentration of 0.140 g/100 ml. Psychostimulants other than cocaine were present in 31.2%. CONCLUSIONS: The 'typical' cocaine-related suicide case was a male, aged in their early thirties, who was highly likely to be employed. The majority of cases used physical means, and a substantial minority were highly agitated and engaged in conflict prior to the fatal incident.

Clinical characteristics of fatal cocaine toxicity in Australia, 2000-2021.

INTRODUCTION: With increased use, the number of cocaine-related deaths has increased. We aimed to determine: (i) the toxicological profile of cocaine, metabolites and adulterants amongst three groups of cocaine-related fatalities in which cocaine and/or metabolites were present in blood: (a) fatal toxicity, where cocaine only (CO) was present (n = 48), (b) multiple drug toxicity (MDT) where other drugs were present (n = 604), and (c) a comparison group of death from traumatic injury (TI, n = 232); (ii) the acute clinical presentation by group; and (iii) cardiovascular disease by group. METHODS: Retrospective study of cocaine-related deaths in Australia, 2000-2021, from the National Coronial Information System. RESULTS: The parent drug cocaine was significantly more common, and had a higher median concentration, amongst the CO group (97.9%, 1.550 mg/L) than the MDT (68.9%, 0.09 mg/L) and TI (70.7%, 0.05 mg/L) groups respectively. Similarly large ratios between CO, MDT and TI were seen for benzoylecgonine (2.100, 0.510, 0.240 mg/L), methylecgonine (1.350, 0.140, 0.070 mg/L), lignocaine (1.200, 0.200, 0.150 mg/L) and levamisole (0.230, 0.045, 0.025 mg/L). The two toxicity groups had significantly higher proportions than the TI group for reports of sudden collapse, seizure, acute psychosis, hyperthermia and vomiting. In addition, CO had higher proportions than MDT and TI of sudden collapse. CO had significantly higher proportions of cardiomegaly and coronary artery disease than the TI group. DISCUSSION AND CONCLUSIONS: Compared to MDT and TI cases, CO cases had higher cocaine concentrations, higher concentrations of adulterants, higher levels of cardiovascular disease and were more likely to suddenly collapse.

Rates, characteristics and toxicology of cocaine-related deaths in Australia, 2000-2021.

AIMS: To (i) assess the population mortality rates of cocaine-related deaths in Australia, 2000 to 2021; (ii) determine the circumstances of death and case characteristics; and (iii) determine their toxicological profile. DESIGN: Retrospective study of cocaine-related deaths in Australia, 2000 to 2021, retrieved from the National Coronial Information System. SETTING: Australia-wide. CASES: A total of 884 cases, mean age = 33.8 (SD, 10.0) years and 86.5% (n = 765) male. MEASUREMENTS: Information was collected on characteristics, manner of death and toxicology. Only cases in which the presence of blood cocaine and/or metabolites were included. FINDINGS: Population rates did not significantly increase during 2001-2011 (annual percentage change [APC] = 1.5; CI, -3.2, 6.5), but from 2012, there was a marked acceleration (APC = 20.0, 95% CI, 15.5, 25.3). Circumstances of death were unintentional drug toxicity (70.7%, n = 625), intentional self-harm (17.8%, n = 157), traumatic accident (11.5%, n = 102). The proportion of cases constituted by unintentional toxicity declined across the study period (APC = -2.6; CI, -3.1, -2.1). There was a substantial decline in the proportion of cases with a history of injecting drug use (APC = -5.7; CI, -6.5, -4.9) and with a history of substance use problems (APC = -3.2; CI, -3.9, -2.5). Both cocaine (0.100 vs 0.050 mg/L, P < 0.001) and benzoylecgonine (0.590 vs 0.240 mg/L, P < 0.001) concentrations were higher amongst toxicity cases than in cases of death from traumatic injury. Cocaethylene was present in 26.4% (n = 233), levamisole in 18.6% (n = 164) and lignocaine in 11.5% (n = 102). Psychoactive drugs in addition to cocaine were present in 92.9% (n = 821), most commonly opioids (50.5%, n = 446), alcohol (47.1%, n = 416), hypnosedatives (43.2%, n = 382) and psychostimulants (30.3%, n = 268). There was a steady decline in the proportion of opioid positive cases (APC = -5.4; CI, -6.3, -4.5). CONCLUSIONS: There was a large increase in cocaine-related deaths across Australia from 2000 to 2021. This was accompanied by changes in case profiles, with histories of injecting drug use and substance use problems, as well as recent opioid use, becoming less prominent.

Hospital service utilisation of people previously hospitalised with different subtypes of psychotic disorder: A record linkage study.

OBJECTIVE: Little research has examined the physical and mental comorbidities, and health service use patterns, of people diagnosed with psychotic disorder subtypes other than schizophrenia spectrum disorders. This study aims to examine the physical and mental comorbidities, and subsequent hospital service use patterns, of individuals previously hospitalised with various psychotic disorder subtypes using linked health service data. METHODS: We included individuals hospitalised with a psychotic disorder in New South Wales, Australia, between 1 July 2002 and 31 December 2014 (N = 63,110). We examined the demographic profile of the cohort and rates of subsequent acute hospital care and ambulatory mental health service use. We compared the rates of subsequent hospital admissions, emergency department presentations and ambulatory mental health treatment days of people hospitalised with different psychotic disorder subtypes to people hospitalised with schizophrenia spectrum disorders using Poisson regression. RESULTS: People most recently hospitalised with mood/affective disorders and psychotic symptoms had a higher rate of subsequent hospital admissions than those most recently hospitalised with schizophrenia spectrum and delusional disorders (adjusted incident rate ratio = 1.06; 95% confidence interval = [1.02, 1.10]), while people most recently hospitalised with drug-induced and other organic (adjusted incident rate ratio = 1.19; 95% confidence interval = [1.12, 1.27]) and acute psychotic disorders (adjusted incident rate ratio = 1.10; 95% confidence interval = [1.03, 1.18]) had more subsequent emergency department presentations than those most recently hospitalised with schizophrenia spectrum and delusional disorders. All three groups had fewer subsequent mental health ambulatory days than those most recently hospitalised with schizophrenia spectrum and delusional disorders (adjusted incident rate ratios = 0.85-0.91). CONCLUSION: The health profiles and subsequent hospital service use patterns of people previously hospitalised with different psychotic disorder subtypes are heterogeneous, and research is needed to develop targeted health policies to meet their specific health needs.

Inequity in smoking cessation clinical trials testing pharmacotherapies: exclusion of smokers with mental health disorders.

OBJECTIVES: People suffering from mental health disorder (MHDs) are often under-represented in clinical research though the reasons for their exclusion are rarely recorded. As they have higher rates of smoking and nicotine dependence, it is crucial that they are adequately represented in clinical trials of established pharmacotherapy interventions for smoking cessation. This review aims to examine the practice of excluding smokers with MHDs and reasons for such exclusion in clinical trials evaluating pharmacotherapy treatments for smoking cessation. DATA SOURCE: The Cochrane database of systematic reviews was searched until September 2020 for reviews on smoking cessation using pharmacotherapies. STUDY SELECTION: Randomised controlled trials (RCTs) within the selected Cochrane reviews were included. DATA EXTRACTION: Conducted by one author and independently verified by three authors. DATA SYNTHESIS: We included 279 RCTs from 13 Cochrane reviews. Of all studies, 51 (18.3%) explicitly excluded participants with any MHDs, 152 (54.5%) conditionally excluded based on certain MHD criteria and 76 (27.2%) provided insufficient information to ascertain either inclusion or exclusion. Studies of antidepressant medications used for smoking cessation were found to be 3.33 times more likely (95% CI 1.38 to 8.01, p=0.007) to conditionally exclude smokers with MHDs than explicitly exclude compared with studies of nicotine replacement therapy. CONCLUSION: Smokers with MHDs are not sufficiently represented in RCTs examining the safety and effectiveness of smoking cessation medications. Greater access to clinical trial participation needs to be facilitated for this group to better address access to appropriate pharmacotherapeutic interventions in this vulnerable population.

Anti-N-Methyl-d-Aspartate Receptor Antibody Testing in First-Episode Psychosis: Universal or Targeted Testing.

Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is an immune-mediated disorder that typically presents with rapid development of neuropsychiatric symptoms. As a potentially reversible cause of psychosis, there have been calls internationally for routine serological screening for anti-NMDAR antibodies in patients presenting with first-episode psychosis (FEP). Increased serological testing has, however, exposed several limitations of universal screening and rekindled debate as to which patients should be tested. Screening criteria have been proposed for high-risk clinical features in FEP in which antineuronal antibody testing is indicated. The authors present a clinical vignette and a service audit as well as discuss the limitations of universal screening advocating instead for targeted testing for antineuronal antibodies in patients diagnosed as having FEP.