Iron Supplementation in Management of Neurodevelopmental Disorders: Systematic Review, Meta-Analysis, and Qualitative Synthesis.

OBJECTIVE: The authors sought to explore the role of iron supplementation in the management of neurodevelopmental disorders among children and youths. METHODS: A systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was undertaken. A subset of results was suitable for meta-analysis. The quality of the evidence and strength of the clinical recommendations were assessed by using the Grading of Recommendations, Assessment, Development, and Evaluation method, and critical appraisal was conducted with the Joanna Briggs Institute critical appraisal tools. RESULTS: Nine articles met inclusion criteria. These articles included studies of attention-deficit hyperactivity disorder (ADHD) (N=7), autism spectrum disorder (N=1), and Tourette's syndrome (N=1). Three randomized controlled trials evaluating iron supplementation for ADHD hyperactivity symptom severity (124 participants: placebo, N=56; supplement, N=68) met inclusion criteria for a meta-analysis. Effect sizes for the placebo and supplement groups were moderate (Cohen's d=0.76) and large (Cohen's d=1.70), respectively, although these differences were not significant. The impact of iron supplementation on inattentive ADHD symptom severity was examined in two trials (75 participants: placebo, N=31; supplement, N=44). Large, nonsignificant effect sizes were demonstrated for the placebo (Cohen's d=1.66) and supplementation (Cohen's d=3.19) groups. The quality of the evidence and strength of the clinical recommendations were considered very low. CONCLUSIONS: Further research is needed to examine the role of iron supplementation in the management of ADHD and neurodevelopmental disorders more generally. Additionally, iron supplementation comes with risks, including death in the case of overdose.

Smoke and mirrors: Support from psychiatrists for nicotine e-cigarette availability in Australia.

The Royal Australian and New Zealand College of Psychiatrists' (RANZCP) 2018 position statement supports increased, regulated availability of e-cigarettes (ECs) as a harm-reduction measure and recommends further research into their use. Aligned with this recommendation, we aimed to critically evaluate the RANZCP's stance on this issue through a literature review focused on the areas identified in the position statement as requiring further investigation: (1) the adverse health effects attributable to ECs; (2) use of ECs for smoking cessation (particularly for people living with severe mental illness); and (3) EC-associated risks for nicotine naïve young people. We identified and summarised evidence of harm attributable to ECs that is particularly relevant to young people through direct adverse health sequelae, onset of nicotine dependence and increased risk of combustible cigarette (CC) use. A small number of studies suggest ECs can be used for harm-reduction purposes in people diagnosed with nicotine dependence and severe mental illness. However, these results must be considered alongside robust evidence supporting the effectiveness of existing pharmacological interventions for smoking cessation in people with severe mental illness. The position statement is in urgent need of review in line with the available evidence.

Long-acting injectable buprenorphine for opioid use disorder: A systematic review of impact of use on social determinants of health.

OBJECTIVES: This systematic review synthesizes evidence on both the effects and perspectives of the use of novel long-acting injectable buprenorphine (LAIB) as part of medication-assisted treatment (MAT) and its impact on social determinants of health (SDH), specifically abstinence, accessibility, employment, forensic matters, and gender and social relationships via a framework approach. METHODS: The study team searched three databases between January 2010 and June 2020 to identify English-language original research published in peer reviewed journals. This search yielded 9253 papers. A comprehensive search followed by 67 full text publication screenings by two independent reviewers yielded 15 papers meeting inclusion criteria. The study included three randomized control trials, one open label safety study, two case series, and six qualitative papers examining patient perspectives toward the LAIB prior to use. The team assessed the quality of studies via standardized quality assessment tools. RESULTS: The LAIB was positively associated with improvements in abstinence, accessibility, employment, social relationships, and forensic matters. Limited evidence exists on gender equity within the current literature. The qualitative papers highlighted the importance of patients' preferences and individualization of treatment planning to ensure the success of MAT. CONCLUSION: The quality of evidence was rated as medium or high risk of bias, which does limit interpretation of the results. Overall, the LAIB was positively associated with SDH and should be offered as part of MAT in alignment with the recovery model. Future research should evaluate the implementation and longitudinal impacts of LAI buprenorphine compared to treatment as usual (TAU).

Quality prescribing in early psychosis: key pharmacotherapy principles.

OBJECTIVE: To present a practical, easy-to-implement clinical framework designed to support evidence-based quality prescribing for people with early psychosis. METHOD: Identification and explanation of key principles relating to evidence-based pharmacotherapy for people with early psychosis. These were derived from the literature, practice guidelines and clinical experience. RESULTS: Key principles include (1) medication choice informed by adverse effects; (2) metabolic monitoring at baseline and at regular intervals; (3) comprehensive and regular medication risk-benefit assessment and psychoeducation; (4) early consideration of long-acting injectable formulations (preferably driven by informed patient choice); (5) identification and treatment of comorbid mood disorders and (6) early consideration of clozapine when treatment refractory criteria are met. CONCLUSIONS: Current prescribing practices do not align with the well-established evidence for quality pharmacotherapy in early psychosis. Adopting evidence-based prescribing practices for people with early psychosis will improve outcomes.

The association between discontinuation of community treatment orders and outcomes in the 12-months following discharge from residential mental health rehabilitation.

To compare the post-discharge outcomes of people admitted to community-based residential mental health rehabilitation facilities subject to a Community Treatment Order (CTO) who do and do not have this order discontinued prior to discharge. People subject to a CTO who were admitted across five Community Care Units (CCUs) in Queensland, Australia between 2005 and 2014 (N = 311), were grouped based on involuntary treatment status at the time of their discharge. Individuals whose status changed to voluntary (n = 63; CTO > VOL) were compared with those whose treatment remained involuntary (n = 248; CTO-CTO) on demographic, clinical and treatment-related characteristics. Group-level and individualised changes were assessed between the year pre-admission and the year post-discharge. The primary outcome measure was change in mental health and social functioning (Health of the Nation Outcome Scale). Secondary outcomes included disability (Life Skills Profile-16), service use, accommodation instability, and involuntary treatment. Logistic regression was completed to examine predictors of CTO discontinuation during CCU care. Potential predictors covered service-, consumer-, and treatment-related characteristics. Compared to the CTO-CTO group, the CTO > VOL group had significantly longer episodes of CCU care, more frequent primary diagnoses of schizophrenia spectrum disorders, and were more likely to be female. Following discharge, CTO > VOL subjects had more frequent reliable and clinically significant improvement in HoNOS scores, as well as more frequently demonstrated reliable improvement in hospital bed use and accommodation instability than the CTO-CTO subjects. CTO discontinuation was predicted by longer duration of CCU care, being a female, and having a smaller number of psychiatry-related bed use prior admission. Our findings suggest that CCU care of sufficient duration may lessen the need for subsequent compulsory treatment in the community.

Predictors of unplanned discharge from community-based residential mental health rehabilitation for people affected by severe and persistent mental illness.

BACKGROUND: Little is known about what predicts disengagement from rehabilitation treatment for people affected by severe and persistent mental illness (SPMI). AIMS: To identify predictors of unplanned discharge among consumers admitted to community-based residential rehabilitation units in Australia. METHOD: Secondary analysis of data from a prospective cohort study of consumers admitted to three Community Care Units (CCUs) between 2014 and 2017 (n = 139). CCUs provide transitional residential rehabilitation support to people affected by SPMI. Demographic, treatment-related and clinical predictors of unplanned discharge were identified using binomial regression models controlling for site-level variability. Factors associated with self- vs staff-initiated unplanned discharge were also examined. RESULTS: 38.8% of consumers experienced unplanned discharge. Significant predictors of unplanned discharge were younger age, higher alcohol consumption and disability associated with mental illness, as well as recovery stage indicating a sense of growth and higher competence in daily task performance. 63.0% of unplanned discharges were initiated by staff, mostly for substance-related reasons (55.9%). History of trauma was more likely among consumers with self-initiated discharge than those with staff-initiated unplanned and planned discharge. CONCLUSIONS: Assertive intervention to address alcohol-use, and ensuring care is trauma-informed, may assist in reducing rates of unplanned discharge from rehabilitation care.

Psychiatric management of anti-NMDAR encephalitis: a cohort analysis.

BACKGROUND: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is an immune-mediated disorder which requires multi-disciplinary treatment including immunomodulation therapy. First presentation is most commonly to psychiatric services and continuing psychiatric care is required to treat disabling symptoms, such as behaviour disturbance, psychosis and catatonia. There is minimal available evidence to guide symptomatic treatment and concern for increased sensitivity to antipsychotics complicates traditional approaches. METHODS: All cases of cerebrospinal fluid positive anti-NMDAR encephalitis tested in Queensland, Australia were identified. Demographic, clinical and therapeutic data were collected and reviewed by two independent clinicians. Pre-specified variables reflecting possible treatment side effects were compared. RESULTS: The majority of the 30 cases (83%) had early psychiatric symptoms and were treated with antipsychotics (67%), average daily olanzapine equivalence dose of 11.5 mg, prior to immunomodulation therapy. Although there was an 88% reduction in cases with aggression, there was little improvement in psychosis, affective symptoms or catatonia with antipsychotics alone. In the cases with psychiatric symptoms, there was no significant difference in the rate of occurrence of neurological and autonomic symptoms between cases prescribed and not prescribed antipsychotics. CONCLUSIONS: Psychiatric input is imperative for both acute and longer-term management of anti-NMDAR encephalitis. Primary symptomatic treatment should remain immunotherapy and surgery. Antipsychotic medications have particular value in managing agitation and aggression. Potential side effects from antipsychotic treatment are difficult to differentiate from progression of anti-NMDAR encephalitis but there was no evidence in this cohort of increased antipsychotic sensitivity. Treatment with psychotropic medication should be individualised and adjusted during the course of the illness.

The Patient Experience of Recovery Following Anti-NMDA Receptor Encephalitis: A Qualitative Content Analysis.

OBJECTIVE: The authors examined patients' perceptions of the factors affecting their recovery from anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis, which is a rare, severe immune-mediated neurological disorder. METHODS: Seven patients completed semistructured interviews exploring their experience of recovery. Participants were interviewed between 7 and 41 months after the initiation of treatment. Interviews were transcribed and subjected to qualitative content analysis. RESULTS: Facilitators of recovery included the presence of a support system and treatment-related factors. Barriers to recovery included perceived psychiatric stigma, insufficient illness education, and lifestyle disruptions to accommodate ongoing treatment. Adverse physical, psychological, and neurocognitive sequelae of anti-NMDAR encephalitis continued to affect participants' daily functioning. Most participants described strategies to manage neurocognitive deficits, fatigue, and anxiety. CONCLUSIONS: Anti-NMDAR encephalitis contributes to persistent burden on patients, their families, and health services after the resolution of acute symptoms. Physical, psychological, and cognitive changes contribute to long-term disease morbidity. To optimize recovery and reduce disability, further attention must be directed toward illness education, reducing stigma, and role disruption. Longer-term disability support may benefit those who do not fully recover.

A Comprehensive Cohort Description and Statistical Grouping of Community-Based Residential Rehabilitation Service Users in Australia.

Background: Community Care Units (CCUs) are a model of community-based residential rehabilitation support available in Australia that assists people affected by severe and persistent mental illness to enhance their independent living skills and community involvement. These services have been subject to limited evaluation, and available descriptions of consumer cohorts lack relevance to the understanding of their rehabilitation needs. Method: A clinical assessment battery covering a broad range of relevant domains was completed with consumers commencing at three CCUs in Queensland, Australia, between December 2014 and December 2017 (N = 145). The cohort was described based on demographic, diagnostic, treatment-related variables, and the assessment battery. The comparability of included sites was assessed. This contemporary cohort was also compared to the pooled cohort of Australian community-based residential rehabilitation services emerging from a previous systematic review. Additionally, cluster analysis (CA) was completed in two stages based on the clinician-rated assessments: hierarchical CA (Wards method) to identify the optimal number of clusters, followed by K-means clustering. Results: Dominant features of the cohort were male sex and the primary diagnoses of schizophrenia spectrum disorders. The average consumer age was 31.4 years. Most consumers were referred from the community, had been living with family, and were not subject to involuntary treatment orders. No site-based differences were observed on demographic, diagnostic and treatment-related variables. However, some site-based variation in levels of symptoms and functional impairment emerged. Overall, the cohort was comparable with the Transitional Residential Rehabilitation (TRR) cohort defined in a previous systematic review. Through CA, a three-cluster solution emerged: Cluster 1 (15%) was characterised by higher levels of substance use comorbidity; Cluster 2 (39%) was characterised by higher levels of disability and symptoms; and Cluster 3 (46%) was distinguished by lower levels of general psychiatric symptoms. Conclusions: The cohort was generally comparable to the TRR cohort. Site-based variability in the characteristics of admitted consumers was minimal. The CA solution suggested that three different sub-groups of consumers are admitted to CCUs, which have implications for adapting the approach to rehabilitation. Recommendations include ensuring early availability of interventions to address co-morbidities and pacing rehabilitation expectations to consumers stage of recovery.

A systematic review of service models and evidence relating to the clinically operated community-based residential mental health rehabilitation for adults with severe and persisting mental illness in Australia.

BACKGROUND: Clinically operated community-based residential rehabilitation units (Community Rehabilitation Units) are resource intensive services supporting a small proportion of the people with severe and persisting mental illness who experience difficulties living in the community. Most consumers who engage with these services will be diagnosed with schizophrenia or a related disorder. This review seeks to: generate a typology of service models, describe the characteristics of the consumers accessing these services, and synthesise available evidence about consumers' service experiences and outcomes. METHOD: A systematic review was undertaken to identify studies describing Community Rehabilitation Units in Australia, consumer characteristics, and evidence about consumer experiences and outcomes. Search strings were applied to multiple databases; additional records were identified through snowballing. Records presenting unique empirical research were subject to quality appraisal. RESULTS: The typology defined two service types, Community-Based Residential Care (C-BRC), which emerged in the context of de-institutionalisation, and the more recent Transitional Residential Rehabilitation (TRR) approach. Key differentiating features were the focus on transitional care and 'recovery' under TRR. Schizophrenia spectrum disorders were the most common primary diagnosis under both service types. TRR consumers were more likely to be male, referred from community settings, and less likely to be subject to involuntary treatment. Regarding outcomes, the limited quantitative evidence (4 records, 2 poor quality) indicated C-BRC was successful in supporting the majority of consumers transferred from long-term inpatient care to remain out of hospital. All qualitative research conducted in C-BRC settings was assessed to be of poor quality (3 records). No methodologically sound quantitative evidence on the outcomes of TRR was identified. Qualitative research undertaken in these settings was of mixed quality (9 records), and the four records exploring consumer perspectives identified them as valuing the service provided. CONCLUSIONS: While there is qualitative evidence to suggest consumers value the support provided by Community Rehabilitation Units, there is an absence of methodologically sound quantitative research about the consumer outcomes achieved by these services. Given the ongoing and increasing investment in these facilities within the Australian context, there is an urgent need for high-quality research examining their efficiency and effectiveness. TRIAL REGISTRATION: PROSPERO ( CRD42018097326 ).

The prevalence and treatment outcomes of antineuronal antibody-positive patients admitted with first episode of psychosis.

BACKGROUND: Antineuronal antibodies are associated with psychosis, although their clinical significance in first episode of psychosis (FEP) is undetermined. AIMS: To examine all patients admitted for treatment of FEP for antineuronal antibodies and describe clinical presentations and treatment outcomes in those who were antibody positive. METHOD: Individuals admitted for FEP to six mental health units in Queensland, Australia, were prospectively tested for serum antineuronal antibodies. Antibody-positive patients were referred for neurological and immunological assessment and therapy. RESULTS: Of 113 consenting participants, six had antineuronal antibodies (anti-N-methyl-D-aspartate receptor antibodies [n = 4], voltage-gated potassium channel antibodies [n = 1] and antibodies against uncharacterised antigen [n = 1]). Five received immunotherapy, which prompted resolution of psychosis in four. CONCLUSIONS: A small subgroup of patients admitted to hospital with FEP have antineuronal antibodies detectable in serum and are responsive to immunotherapy. Early diagnosis and treatment is critical to optimise recovery. DECLARATION OF INTEREST: None.

Cognitive outcomes following anti-N-methyl-D-aspartate receptor encephalitis: A systematic review.

INTRODUCTION: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an immune-mediated neurological disorder that (among other severe neuropsychiatric symptoms) affects cognition. This study aimed to summarize current knowledge regarding the rates, nature, and predictors of neuropsychological dysfunction in patients recovering from anti-NMDAR encephalitis. METHOD: A systematic review of studies describing neuropsychological outcomes following anti-NMDAR encephalitis was conducted. Electronic databases Medline, PsycINFO, EMBASE, and CINAHL were searched from inception to September 2016. Results were summarized using descriptive statistics and a series of chi-square analyses. RESULTS: Of 4030 identified studies, 44 were included. These reported neuropsychological outcomes for 109 treated patients (83.5% female, Mage = 22.5 years, range = 2-67) recovering from anti-NMDAR encephalitis. High rates of neuropsychological dysfunction were identified, with diverse impairments of variable severity documented in >75% of patients at assessments conducted during acute, subacute, and longer term recovery periods. Despite this, cognitive outcomes were ultimately considered favorable in most cases (74.3%). This estimate does not account for the potential impact of relapses. The frequency of impairments in overall intellectual functioning, language, attention, working memory, and visuospatial functions were significantly higher within the acute recovery period than in later phases of convalescence. However, rates of impaired processing speed, episodic memory, and aspects of executive functioning were consistent across time points. Adverse neuropsychological outcomes occurred at significantly higher frequency in patients where immunotherapy was delayed, χ2(1, N = 66) = 10.84, p < .003. CONCLUSIONS: Neuropsychological deficits are prevalent at all points of recovery from anti-NMDAR encephalitis, although improvement in cognitive outcomes can be expected as patients recover. Some cognitive deficits may be less likely than others to resolve. Close neuropsychological monitoring is warranted in this population. Longitudinal studies of neuropsychological functioning of patients with anti-NMDAR encephalitis are needed to accurately inform prognosis.

Cognitive and Social Functioning Deficits after Anti-N-Methyl-D-Aspartate Receptor Encephalitis: An Exploratory Case Series.

BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a recently described life-threatening autoimmune disorder associated with a characteristic multi-stage neuropsychiatric syndrome. Although it is known that the majority of patients experience neuropsychological disturbance post-treatment, some aspects of the cognitive profile remain unclear. METHODS: This study sought to investigate patterns of cognitive functioning in a sample of anti-NMDAR encephalitis patients. Seven (6F:1M; mean age, 26.4 years; range, 16-37 years) treated patients completed a comprehensive set of neurocognitive and social functioning measures. Performance was analyzed using normative data (where available), and comparison with matched controls (10F:4M; mean age, 25.8 years; range, 16-38 years). RESULTS: Individual cognitive profiles ranged from within normal limits to extensive dysfunction. Relative to controls, the patient group's performance was affected in the domains of verbal/ visual memory, working memory, attention, processing speed, executive functioning, and social cognition. The patient group also reported significantly higher levels of anxiety compared to controls. CONCLUSIONS: These results add to the accumulating evidence that neurocognitive deficits, consistent with the distribution and functions of the NMDAR system can persist during recovery from anti-NMDAR encephalitis. This is the first study to provide evidence of performance decrements on measures of social cognition, including some involving theory of mind. (JINS, 2016, 22, 828-838).

System-level intersectoral linkages between the mental health and non-clinical support sectors: a qualitative systematic review.

OBJECTIVES: Concerns about fragmented mental health service delivery persist, particularly for people with severe and persistent mental illness. The objective was to review evidence regarding outcomes attributed to system-level intersectoral linkages involving mental health services and non-clinical support services, and to identify barriers and facilitators to the intersectoral linkage process. METHODS: A systematic, qualitative review of studies describing attempts to coordinate the activities of multiple service agencies at the policy, program or organisational level was conducted. Electronic databases Medline, PsycINFO and EMBASE were searched via OVID from inception to July 2012. RESULTS: Of 1593 studies identified, 40 were included in the review - 26 in adult and 14 in vulnerable youth populations. Identified mechanisms to promote positive system-level outcomes included: interagency coordinating committees or intersectoral/interface workers engaged in joint service planning; formalised interagency collaborative agreements; a single care plan in which the responsibilities of all agencies are described; cross-training of staff to ensure staff culture, attitudes, knowledge and skills are complementary; service co-location; and blended funding initiatives to ensure funding aligns with program integration. Identified barriers included: adequacy of funding and technology; ensuring realistic workloads; overcoming 'turf issues' between service providers and disagreements regarding areas of responsibility; ensuring integration strategies are implemented as planned; and maintaining stakeholder enthusiasm. CONCLUSIONS: System-level intersectoral linkages can be achieved in various ways and are associated with positive clinical and non-clinical outcomes for services and clients. Some linkage mechanisms present greater implementation challenges than others (e.g. major technology upgrades or co-location in geographically remote areas). In some instances (e.g. co-location) alternative options may achieve equivalent benefits. Publication bias could not be discounted, and studies using high-quality research designs are scarce. The limited information base applicable to system-level integration argues strongly for the evaluation of the models that evolve in the rollout of the national Partners in Recovery initiative.