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.

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.

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.

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.

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.

The health service contact patterns of people with psychotic and non-psychotic forms of severe mental illness in New South Wales, Australia: A record-linkage study.

OBJECTIVE: To describe and compare the health profiles and health service use of people hospitalised with severe mental illness, with and without psychotic symptoms. METHODS: We conducted a historical cohort study using linked administrative datasets, including data on public hospital admissions, emergency department presentations and ambulatory mental health service contacts in New South Wales, Australia. The study cohort comprised 169,306 individuals aged 12 years and over who were hospitalised at least once with a mental health diagnosis between 1 July 2002 and 31 December 2014. Of these, 63,110 had a recorded psychotic illness and 106,196 did not. Outcome measures were rates of hospital, emergency department and mental health ambulatory service utilisation, analysed using Poisson regression. RESULTS: People with psychotic illnesses had higher rates of hospital admission (adjusted incidence rate ratio (IRR) 1.26; 95% confidence interval [1.23, 1.30]), emergency department presentation (adjusted IRR 1.17; 95% confidence interval [1.13, 1.20]) and ambulatory mental health treatment days (adjusted IRR 2.90; 95% confidence interval [2.82, 2.98]) than people without psychotic illnesses. The higher rate of hospitalisation among people with psychotic illnesses was driven by mental health admissions; while people with psychosis had over twice the rate of mental health admissions, people with other severe mental illnesses without psychosis (e.g. mood/affective, anxiety and personality disorders) had higher rates of physical health admissions, including for circulatory, musculoskeletal, genitourinary and respiratory disorders. Factors that predicted greater health service utilisation included psychosis, intellectual disability, greater medical comorbidity and previous hospitalisation. CONCLUSION: Findings from this study support the need for (a) the development of processes to support the physical health of people with severe mental illness, including those without psychosis; (b) a focus in mental health policy and service provision on people with complex support needs, and (c) improved implementation and testing of integrated models of care to improve health outcomes for all people experiencing severe mental illness.

Depression and anxiety in relation to cancer incidence and mortality: a systematic review and meta-analysis of cohort studies.

The link between depression and anxiety status and cancer outcomes has been well-documented but remains unclear. We comprehensively quantified the association between depression and anxiety defined by symptom scales or clinical diagnosis and the risk of cancer incidence, cancer-specific mortality, and all-cause mortality in cancer patients. Pooled estimates of the relative risks (RRs) for cancer incidence and mortality were performed in a meta-analysis by random effects or fixed effects models as appropriate. Associations were tested in subgroups stratified by different study and participant characteristics. Fifty-one eligible cohort studies involving 2,611,907 participants with a mean follow-up period of 10.3 years were identified. Overall, depression and anxiety were associated with a significantly increased risk of cancer incidence (adjusted RR: 1.13, 95% CI: 1.06-1.19), cancer-specific mortality (1.21, 1.16-1.26), and all-cause mortality in cancer patients (1.24, 1.13-1.35). The estimated absolute risk increases (ARIs) associated with depression and anxiety were 34.3 events/100,000 person years (15.8-50.2) for cancer incidence and 28.2 events/100,000 person years (21.5-34.9) for cancer-specific mortality. Subgroup analyses demonstrated that clinically diagnosed depression and anxiety were related to higher cancer incidence, poorer cancer survival, and higher cancer-specific mortality. Psychological distress (symptoms of depression and anxiety) was related to higher cancer-specific mortality and poorer cancer survival but not to increased cancer incidence. Site-specific analyses indicated that overall, depression and anxiety were associated with an increased incidence risks for cancers of the lung, oral cavity, prostate and skin, a higher cancer-specific mortality risk for cancers of the lung, bladder, breast, colorectum, hematopoietic system, kidney and prostate, and an increased all-cause mortality risk in lung cancer patients. These analyses suggest that depression and anxiety may have an etiologic role and prognostic impact on cancer, although there is potential reverse causality; Furthermore, there was substantial heterogeneity among the included studies, and the results should be interpreted with caution. Early detection and effective intervention of depression and anxiety in cancer patients and the general population have public health and clinical importance.

Cognitive improvement among abstinent methamphetamine users: A 2-year prospective longitudinal study.

BACKGROUND AND OBJECTIVES: The adverse impact of chronic methamphetamine (MA) use on cognitive function has been described in previous studies, but limited evidence is available for abstinent users from prospective longitudinal studies. The aim of the present study was to assess cognitive function of varying abstinent duration. METHODS: This prospective longitudinal study was conducted with baseline and four follow-up interviews every 6 months over 2 years in 358 MA users in Guangdong province, China. The Montreal Cognitive Assessment (MoCA) was used to measure cognitive function. Generalized estimating equation (GEE) analysis was used to examine within-subjects relationships between abstinence and cognitive consequences over time. RESULTS: The repeated measure analysis of variance showed significant differences in the total MoCA score and all subscale scores (except Orientation) in the 24 months follow-up. The GEE model showed that abstinence from MA in the past 6 months predicted an increase of 0.66 (95% confidence interval [CI] = 0.29 to 1.05, p = .002) in MoCA score changes compared with the nonabstinence MA users. Abstinence in the past 12, 18, and 24 months predicted an increase in MoCA total score changes of 1.25 (95% CI = -0.23 to 2.74), 2.15 (95% CI = -0.79 to 5.09), and 5.28 (95% CI = -2.01 to 12.58), respectively, but none of these was statistically significant. DISCUSSION AND CONCLUSIONS: Cognitive function was potentially improved following 6 months of MA abstinence. SCIENTIFIC SIGNIFICANCE: This study extends prior research by long-term follow-up in big sample MA abstinence users. Findings from study support the need for a comprehensive measure to decrease MA use and promote the recovery of cognitive impairment.

Diagnostic stability and outcome after first episode psychosis.

BACKGROUND: Individuals diagnosed with schizophrenia are often assigned other psychiatric diagnoses during their lives. The significance of changing diagnosis has not been widely studied. AIMS: Our aim was to examine the association between diagnostic change and later outcome. METHODS: Individuals' diagnostic history, clinical and social outcomes were extracted from the AESOP-10 study, a 10-year follow-up of first episode psychosis cases. The association between outcome and different patterns of diagnosis over time were assessed using linear or logistic regression. RESULTS: Individuals always diagnosed with schizophrenia (n = 136) had worse clinical and social outcomes at follow-up than those never diagnosed with schizophrenia (n = 163), being more likely to be symptomatic, unemployed, single, and socially isolated. There was no difference in outcome between individuals always diagnosed with schizophrenia and those changing to a diagnosis of schizophrenia (n = 60), and no difference in outcome between individuals never diagnosed with schizophrenia, and those changing from a diagnosis of schizophrenia (n = 44). CONCLUSIONS: Individuals always and never diagnosed with schizophrenia had different outcomes. In cases of diagnostic instability participants had similar outcomes to those always assigned the diagnosis they changed to irrespective of initial diagnosis.

Symptom remission at 12-weeks strongly predicts long-term recovery from the first episode of psychosis.

BACKGROUND: To determine the baseline individual characteristics that predicted symptom recovery and functional recovery at 10-years following the first episode of psychosis. METHODS: AESOP-10 is a 10-year follow up of an epidemiological, naturalistic population-based cohort of individuals recruited at the time of their first episode of psychosis in two areas in the UK (South East London and Nottingham). Detailed information on demographic, clinical, and social factors was examined to identify which factors predicted symptom and functional remission and recovery over 10-year follow-up. The study included 557 individuals with a first episode psychosis. The main study outcomes were symptom recovery and functional recovery at 10-year follow-up. RESULTS: At 10 years, 46.2% (n = 140 of 303) of patients achieved symptom recovery and 40.9% (n = 117) achieved functional recovery. The strongest predictor of symptom recovery at 10 years was symptom remission at 12 weeks (adj OR 4.47; CI 2.60-7.67); followed by a diagnosis of depression with psychotic symptoms (adj OR 2.68; CI 1.02-7.05). Symptom remission at 12 weeks was also a strong predictor of functional recovery at 10 years (adj OR 2.75; CI 1.23-6.11), together with being from Nottingham study centre (adj OR 3.23; CI 1.25-8.30) and having a diagnosis of mania (adj OR 8.17; CI 1.61-41.42). CONCLUSIONS: Symptom remission at 12 weeks is an important predictor of both symptom and functional recovery at 10 years, with implications for illness management. The concepts of clinical and functional recovery overlap but should be considered separately.

Prevalence and correlates of food insecurity in community-based individuals with severe mental illness receiving long-acting injectable antipsychotic treatment.

People with severe mental illness (SMI) have numerous risk factors that may predispose them to food insecurity (FI); however, the prevalence of FI and its effects on health are under-researched in this population. The present study aimed to describe the prevalence of FI and its relationship to lifestyle factors in people with SMI. This cross-sectional study recruited people with SMI receiving long-acting injectable (LAI) antipsychotic medication from community services at three sites in Sydney, Australia. Assessments were completed on physical health and lifestyle factors. χ2 Tests, independent-samples t tests and binary logistic regression analyses were calculated to examine relationships between lifestyle factors and FI. In total, 233 people completed the assessments: 154 were males (66 %), mean age 44·8 (sd 12·7) years, and the majority (70 %) had a diagnosis of schizophrenia. FI was present in 104 participants (45 %). People with FI were less likely to consume fruits (OR 0·42, 95 % CI 0·24, 0·74, P = 0·003), vegetables (OR 0·39, 95 % CI 0·22, 0·69, P = 0·001) and protein-based foods (OR 0·45, 95 % CI 0·25, 0·83, P = 0·011) at least once daily, engaged in less moderate to vigorous physical activity (min) (OR 0·997, 95 % CI 0·993, 1·000, P = 0·044), and were more likely to smoke (OR 1·89, 95 % CI 1·08, 3·32, P = 0·026). FI is highly prevalent among people with SMI receiving LAI antipsychotic medications. Food-insecure people with SMI engage in less healthy lifestyle behaviours, increasing the risk of future non-communicable disease.

Targeted Intervention to Reduce Smoking among People with Severe Mental Illness: Implementation of a Smoking Cessation Intervention in an Inpatient Mental Health Setting.

Background and Objectives: Smoking and smoking-related harms are highly prevalent among people with severe mental illness. Targeted smoking cessation programs are much needed in this population. This pilot study aimed to assess the effectiveness of implementing smoking cessation system change interventions within an acute inpatient mental health unit. Materials and Methods: Design: Pre-post intervention study. System change interventions for smoking cessation were delivered over a three-month period (05 March 2018-04 June 2018) on an acute inpatient mental health unit. Participants (n = 214) were all individuals receiving care as inpatients during the three-month intervention. Outcomes assessed pre- and post-intervention were: (i) recording of patient smoking status in medical notes, (ii) number of inpatients offered smoking cessation medication, and iii) number of violent incidents reported. Results: Recording of smoking status significantly increased from 1.9% to 11.4% (X2 = 14.80; p ≤ 0.001). The proportion of inpatients offered smoking cessation treatment significantly increased from 11.0% to 26.8% (X2 = 16.01; p ≤ 0.001). The number of violent incidents decreased by half, which was not statistically significant. Conclusion: Evidence-based smoking cessation interventions can be successfully implemented on an inpatient mental health unit. Modest gains were made in routine screening for smoking and in smoking cessation treatment prescription. Future studies should prioritize effective participatory collaboration with staff to optimize effectiveness of interventions and should include additional strategies such as brief intervention training and smoking cessation treatments such as varenicline and buproprion in addition to nicotine replacement therapy (NRT).

Fatal Stroke in Pregnancy and the Puerperium.

Background and Purpose- Fatal stroke during pregnancy and the puerperium is rare. Pregnancy-related hypertension and vascular abnormalities underlie significant proportions of pregnancy-related stroke, but up to one-quarter are of no known cause. Methods- Case series of fatal pregnancy-related stroke. All cases where the cause of death was attributed to stroke during pregnancy/postpartum were retrieved from the National Coronial Information System database (January 1, 2009 to December 31, 2016). Results- Fourteen fatal strokes were identified, all hemorrhagic in origin. Underlying causes included pregnancy-related hypertension, rupture of vascular malformations, vasculitis, and cardiomyopathy. Conclusions- Fatal pregnancy-related stroke occurred secondary to hemorrhages of heterogeneous causes, including pregnancy-related hypertension and previously undiagnosed risk factors.

Stroke and methamphetamine use in young adults: a review.

BACKGROUND: Methamphetamine use and stroke are significant public health problems. Strokes among people aged below 45 years are much less common than in older age groups but have significant mortality and morbidity. Methamphetamine is a putative cause of strokes among younger people. METHODS: A review of methamphetamine-related strokes was conducted. Bibliographic databases were searched until February 2017 for articles related to methamphetamine and stroke. Both haemorrhagic and ischaemic strokes were considered. RESULTS: Of 370 articles screened, 77 were selected for inclusion. There were 81 haemorrhagic and 17 ischaemic strokes reported in case reports and series. Both types were approximately twice as common in males. Route of administration associated with haemorrhagic stroke was typically oral or injecting, but for ischaemic stroke inhalation was most common. Haemorrhagic stroke was associated with vascular abnormalities in a third of cases. One quarter of individuals completely recovered, and a third died following haemorrhagic stroke. One-fifth completely recovered, and one-fifth died following ischaemic stroke. CONCLUSIONS: There is a preponderance of haemorrhagic strokes associated with methamphetamine use in young people, and methamphetamine-related stroke is associated with poor clinical outcomes. Mechanisms of methamphetamine-associated stroke include hypertension, vasculitis, direct vascular toxicity and vasospasm. In a period of rising worldwide methamphetamine use, the incidence of methamphetamine-related stroke will increase, with a consequent increase in the burden of disease contributed by such events.

Outcomes following first-episode psychosis - Why we should intervene early in all ages, not only in youth.

OBJECTIVE: To compare baseline demographics and 10-year outcomes of a first-episode psychosis patient incidence cohort in order to establish whether current youth-focussed age-based criteria for early intervention services are justified by patient needs. The patients in this cohort were treated prior to the establishment of early intervention services. The study aimed to test the hypothesis that those who develop psychosis at a younger age have worse outcomes than those who develop psychosis at an older age. METHODS: Data on first-episode psychosis patients from the ÆSOP-10 longitudinal follow-up study were used to compare baseline characteristics, and 10-year clinical, functional and service use outcomes between those patients who would and would not have met age-based criteria for early intervention services, in Australia or in the United Kingdom. RESULTS: In total, 58% men and 71% women with first-episode psychosis were too old to meet current Australian-early intervention age-entry criteria (χ2 = 9.1, p = 0.003), while 21% men and 34% women were too old for UK-early intervention age-entry criteria (χ2 = 11.1, p = 0.001). The 10-year clinical and functional outcomes did not differ significantly between groups by either Australian- or UK-early intervention age-entry criteria. Service use was significantly greater among the patients young enough to meet early intervention age-criteria (Australia: incidence rate ratio = 1.35 [1.19, 1.52], p < 0.001; United Kingdom: incidence rate ratio = 1.65 [1.41, 1.93], p < 0.001). CONCLUSION: Current early intervention services are gender- and age-inequitable. Large numbers of patients with first-episode psychosis will not receive early intervention care under current service provision. Illness outcomes at 10-years were no worse in first-episode psychosis patients who presented within the age range for whom early intervention has been prioritised, though these patients had greater service use. These data provide a rationale to consider extension of early intervention to all, rather than just to youth.

Limbic striatal dopamine D2/3 receptor availability is associated with non-planning impulsivity in healthy adults after exclusion of potential dissimulators.

Positron emission tomography (PET) studies have reported an association between reduced striatal dopamine D2/3 receptor availability and higher scores on self-report measures of trait impulsivity in healthy adults. However, impulsivity is a multi-faceted construct, and it is unclear which aspect(s) of impulsivity might be driving these associations. The current study aimed to investigate the relationship between limbic (ventral) striatal D2/3 receptor availability and individual components of impulsivity (attentional, motor and non-planning) using the Barratt Impulsiveness Scale (BIS-11) and [(11)C]raclopride PET in 23 healthy volunteers. A partial correlational analysis showed a significant association between non-planning impulsiveness (lack of forethought or 'futuring') and limbic D2/3 receptor availability, which was only apparent after the exclusion of potential dissimulators (indexed by high scores on impression management). Our findings suggest that non-planning impulsiveness is associated with individual variation in limbic striatal D2/3 receptor availability and that different facets of impulsivity may have specific neurochemical correlates. Future studies that combine D2/3 receptor imaging with behavioral measures of impulsivity are required to further elucidate the precise relationship between individual components of trait impulsivity and brain dopaminergic function.