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Background: The rate of transition to psychotic disorder in ultra high risk (UHR) patients has declined in recent cohorts. The reasons for this are unclear, but may include a lead-time bias, earlier intervention, a change in clinical characteristics of cohorts, and treatment changes.Aims: In this paper we examined the two possibilities related to reduction in duration of symptoms prior to clinic entry, i.e., lead-time bias and earlier intervention.Method: The sample consisted of all UHR research participants seen at the PACE clinic, Melbourne between 1993 and 2006 (N=416), followed for a mean of 7.5years (the 'PACE 400' cohort). Duration of symptoms was analysed by four baseline year time periods. Analysis of transition rate by duration of symptoms was restricted to more homogenous sub-samples (pre-1998 and pre-2001) in order to minimize confounding effects of change in patient characteristics or treatments. These cohorts were divided into those with a short and long duration of symptoms using a cut-point approach.Results: Duration of symptoms prior to entry did not reduce significantly between 1993 and 2006 (p=0.10). The group with a short duration of symptoms showed lower transition rates and did not catch up in transition rate compared to the long duration of symptoms group.Discussion: These data suggest that, while earlier intervention or lead-time bias do not fully account for the declining transition rate in UHR cohorts, it appears that earlier intervention may have exerted a stronger influence on this decline than length of follow-up period (lead-time bias). [ABSTRACT FROM AUTHOR]

Background.Individuals identified as at ultra-high risk (UHR) for psychosis are at risk of poor functional outcome regardless of development of psychotic disorder. Studies examining longitudinal predictors of poor functioning have tended to be small and report only medium-term follow-up data. We sought to examine clinical predictors of functional outcome in a long-term longitudinal study.Method.Participants were 268 (152 females, 116 males) individuals identified as UHR 2–14 years previously. A range of clinical and sociodemographic variables were assessed at baseline. Functioning at follow-up was assessed using the Social and Occupational Functioning Assessment Scale (SOFAS).Results.Baseline negative symptoms, impaired emotional functioning, disorders of thought content, low functioning, past substance use disorder and history of childhood maltreatment predicted poor functioning at follow-up in univariate analyses. Only childhood maltreatment remained significant in the multivariate analysis (p < 0.001). Transition to psychosis was also significantly associated with poor functioning at long-term follow-up [mean SOFAS score 59.12 (s.d. = 18.54) in the transitioned group compared to 70.89 (s.d. = 14.00) in the non-transitioned group, p < 0.001]. Childhood maltreatment was a significant predictor of poor functioning in both the transitioned and non-transitioned groups.Conclusions.Childhood maltreatment and transition to psychotic disorder independently predicted poor long-term functioning. This suggests that it is important to assess history of childhood maltreatment in clinical management of UHR individuals. The finding that transition to psychosis predicts poor long-term functioning strengthens the evidence that the UHR criteria detect a subgroup at risk for schizophrenia. [ABSTRACT FROM PUBLISHER]

BackgroundIndividuals at ultra-high risk (UHR) for psychosis show reduced neurocognitive performance across domains but it is unclear which reductions are associated with transition to frank psychosis. The aim of this study was to investigate differences in baseline neurocognitive performance between UHR participants with (UHR-P) and without transition to psychosis (UHR-NP) and a healthy control (HC) group and examine neurocognitive predictors of transition over the medium to long term.MethodA sample of 325 UHR participants recruited consecutively from the Personal Assessment and Crisis Evaluation (PACE) Clinic in Melbourne and 66 HCs completed a neurocognitive assessment at baseline. The UHR group was followed up between 2.39 and 14.86 (median = 6.45) years later. Cox regression was used to investigate candidate neurocognitive predictors of psychosis onset.ResultsThe UHR group performed more poorly than the HC group across a range of neurocognitive domains but only performance on digit symbol coding and picture completion differed between the groups. The risk of transition was only significantly associated with poorer performance on visual reproduction [hazard ratio (HR) 0.919, 95% confidence interval (CI) 0.876–0.965, p = 0.001] and matrix reasoning (HR 0.938, 95% CI 0.883–0.996, p = 0.037). These remained significant even after controlling for psychopathology at baseline.ConclusionsThis study is the longest follow-up of an UHR sample to date. UHR status was associated with poorer neurocognitive performance compared to HCs on some tasks. Cognition at identification as UHR was not a strong predictor of risk for transition to psychosis. The results suggests the need to include more experimental paradigms that isolate discrete cognitive processes to better understand neurocognition at this early stage of illness. [ABSTRACT FROM PUBLISHER]

BackgroundSubclinical psychotic experiences during adolescence may represent liability for developing psychotic disorder. Both coping style and the degree of persistence of psychotic experiences may play a role in the progression to clinical psychotic disorder, but little is known about the causal relationship between the two.MethodPath modelling was used to examine longitudinal relationships between subclinical positive psychotic experiences and three styles of coping (task-, emotion- and avoidance-oriented) in an adolescent general population sample (n=813) assessed three times in 3 years. Distinct developmental trajectories of psychotic experiences, identified with growth mixture modelling, were compared on the use of these coping styles.ResultsOver time, emotion-oriented coping in general was bi-directionally related to psychotic experiences. No meaningful results were found for task- or avoidance-oriented coping. Females reported using a wider range of coping styles than males, but the paths between coping and psychotic experiences did not differ by gender. Persistence of psychotic experiences was associated with a greater use of emotion-oriented coping, whereas a decrease in experiences over time was associated with an increased use of task-orientated coping.ConclusionsEmotion-oriented coping is the most important coping style in relation to psychotic experiences, as it may contribute to a ‘vicious cycle’ and is associated with persistence of experiences. In addition, more task-oriented coping may result in a decrease in psychotic experiences. Results suggest that opportunities for intervention may already be present at the level of subclinical psychosis. [ABSTRACT FROM PUBLISHER]

Psychotic symptoms are typically measured using clinical ratings, but more objective and sensitive metrics are needed. Hence, we will assess thought disorder using the Research Domain Criteria (RDoC) heuristic for language production, and its recommended paradigm of "linguistic corpus-based analyses of language output". Positive thought disorder (e.g., tangentiality and derailment) can be assessed using word-embedding approaches that assess semantic coherence, whereas negative thought disorder (e.g., concreteness, poverty of speech) can be assessed using part-of-speech (POS) tagging to assess syntactic complexity. We aim to establish convergent validity of automated linguistic metrics with clinical ratings, assess normative demographic variance, determine cognitive and functional correlates, and replicate their predictive power for psychosis transition among at-risk youths. This study will assess language production in 450 English-speaking individuals in Australia and Canada, who have recent onset psychosis, are at clinical high risk (CHR) for psychosis, or who are healthy volunteers, all well-characterized for cognition, function and symptoms. Speech will be elicited using open-ended interviews. Audio files will be transcribed and preprocessed for automated natural language processing (NLP) analyses of coherence and complexity. Data analyses include canonical correlation, multivariate linear regression with regularization, and machine-learning classification of group status and psychosis outcome. This prospective study aims to characterize language disturbance across stages of psychosis using computational approaches, including psychometric properties, normative variance and clinical correlates, important for biomarker development. SPEAK will create a large archive of language data available to other investigators, a rich resource for the field. [ABSTRACT FROM AUTHOR]

Background: Multimodal modeling that combines biological and clinical data shows promise in predicting transition to psychosis in individuals who are at ultra-high risk. Individuals who transition to psychosis are known to have deficits at baseline in cognitive function and reductions in gray matter volume in multiple brain regions identified by magnetic resonance imaging., Methods: In this study, we used Cox proportional hazards regression models to assess the additive predictive value of each modality-cognition, cortical structure information, and the neuroanatomical measure of brain age gap-to a previously developed clinical model using functioning and duration of symptoms prior to service entry as predictors in the Personal Assessment and Crisis Evaluation (PACE) 400 cohort. The PACE 400 study is a well-characterized cohort of Australian youths who were identified as ultra-high risk of transitioning to psychosis using the Comprehensive Assessment of At Risk Mental States (CAARMS) and followed for up to 18 years; it contains clinical data (from N = 416 participants), cognitive data (n = 213), and magnetic resonance imaging cortical parameters extracted using FreeSurfer (n = 231)., Results: The results showed that neuroimaging, brain age gap, and cognition added marginal predictive information to the previously developed clinical model (fraction of new information: neuroimaging 0%-12%, brain age gap 7%, cognition 0%-16%)., Conclusions: In summary, adding a second modality to a clinical risk model predicting the onset of a psychotic disorder in the PACE 400 cohort showed little improvement in the fit of the model for long-term prediction of transition to psychosis., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background and Hypotheses: Sleep disturbances are increasingly recognized as cooccurring with psychotic symptoms. The potential importance of this relationship is complicated when considering the effects of anxiety and depressive symptoms which commonly present in early-stage illness states. This study aimed to investigate the relationship between self-reported sleep disturbance on the development of attenuated psychotic symptoms (APS) cross-sectionally and longitudinally while adjusting for roles of anxiety and depressive symptoms., Design: Eight-hundred and two help-seeking young people aged 12 to 25 years who engaged with our Australian early intervention services were included in the study (the "Transitions" cohort). Cross sectional mediation and cross-lagged longitudinal (12-month) mediation models were developed with outcomes being different APS domains., Results: Only baseline excessive daytime sleepiness predicted later APS when accounting for previous APS, anxiety and depressive symptomatology. Cross sectionally, self-reported sleep disturbance showed both direct and indirect predictive relationships with all APS domains. Partial mediation through anxiety and depression was shown for unusual thought content, perceptual abnormalities, and disorganised speech, while full mediation through depression was shown for non-bizarre ideas., Conclusions: The specificity of the relationship between self-reported sleep disturbance on APS highlights the potential for different roles in mechanistic models of psychotic symptom expression. This further indicates the need for further experimental research to illuminate potential causal pathways. Future research should continue to use continuous, symptom level approaches across a range of timeframes to more accurately model the complex dynamics present in the sleep-psychosis relationship., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The drivers of cognitive change following first-episode psychosis remain poorly understood. Evidence regarding the role of antipsychotic medication is primarily based on naturalistic studies or clinical trials without a placebo arm, making it difficult to disentangle illness from medication effects. A secondary analysis of a randomised, triple-blind, placebo-controlled trial, where antipsychotic-naive patients with first-episode psychotic disorder were allocated to receive risperidone/paliperidone or matched placebo plus intensive psychosocial therapy for 6 months was conducted. A healthy control group was also recruited. A cognitive battery was administered at baseline and 6 months. Intention-to-treat analysis involved 76 patients (antipsychotic medication group: 37; 18.6 Mage [2.9] years; 21 women; placebo group: 39; 18.3 Mage [2.7]; 22 women); and 42 healthy controls (19.2 Mage [3.0] years; 28 women). Cognitive performance predominantly remained stable (working memory, verbal fluency) or improved (attention, processing speed, cognitive control), with no group-by-time interaction evident. However, a significant group-by-time interaction was observed for immediate recall (p = 0.023), verbal learning (p = 0.024) and delayed recall (p = 0.005). The medication group declined whereas the placebo group improved on each measure (immediate recall: p = 0.024; η p 2  = 0.062; verbal learning: p = 0.015; η p 2  = 0.072 both medium effects; delayed recall: p = 0.001; η p 2  = 0.123 large effect). The rate of change for the placebo and healthy control groups was similar. Per protocol analysis (placebo n = 16, medication n = 11) produced similar findings. Risperidone/paliperidone may worsen verbal learning and memory in the early months of psychosis treatment. Replication of this finding and examination of various antipsychotic agents are needed in confirmatory trials. Antipsychotic effects should be considered in longitudinal studies of cognition in psychosis.Trial registration: Australian New Zealand Clinical Trials Registry ( http://www.anzctr.org.au/ ; ACTRN12607000608460)., (© 2023. The Author(s).)

Objectives: The field of early psychosis has undergone considerable expansion over the last few decades and has a strong evidence base of effectiveness. Like all areas of healthcare, however, early psychosis services need to more consistently deliver higher quality care to achieve better outcomes for patients and families. A national clinical research infrastructure is urgently required to enable the sector to deliver the highest quality care and expand and translate evidence more quickly and efficiently. This paper describes the establishment of the Australian Early Psychosis Collaborative Consortium (AEPCC) that aims to achieve this., Conclusion: AEPCC is the first of its kind in Australia (and internationally). It will deliver the required clinical research infrastructure through the implementation of a clinical quality registry, clinical trials and translation network, and lived experience network. AEPCC will provide a critical resource to better understand the state of early psychosis care, and trial new interventions on a scale that has not previously been possible in Australia.

Background: There is a higher incidence of psychotic disorders in neighbourhoods of greater social deprivation. However, it is not known whether this represents a causal relationship, as the stage at which social deprivation exerts its influence on the development of psychotic disorders is yet to be elucidated. We aimed to investigate the association between neighbourhood-level social deprivation and the rate of identification of individuals at Ultra-High Risk for psychosis (UHR), as well as the risk of transition to psychosis in UHR individuals., Methods: The cohort included all young people aged 15 to 24 identified as UHR attending an Early Intervention clinic in northwestern Melbourne over a 5-year period (2012-2016). Australian census data were used to obtain the at-risk population and social deprivation information according to the postcode of residence. Levels of social deprivation were arranged into quartiles. Poisson regression was used to calculate rate ratios and Cox regression analysis determined hazard ratios., Results: Of the 461 young people identified as UHR, 11.1% ( n  = 49) lived in the most affluent neighbourhoods (Quartile 1) compared to 36.7% ( n  = 162) in the most deprived neighbourhoods (Quartile 4). There was a 35% higher rate of identification of young people who were UHR from the most deprived neighbourhoods (aIRR = 1.35, 95% CI [0.98, 1.86]). Over a median follow-up of approximately 10 months (308 days (IQR: 188-557), 17.5% ( n  = 77) were known to have transitioned to a full-threshold psychotic disorder. Residing in a neighbourhood of above average deprivation had a hazard ratio of 2.05 (95% CI [0.88, 4.80]) for risk of transition, when controlling for age, sex and substance use., Conclusions: These findings provide more support that EI services should be funded as per the expected incidence of psychotic disorders.

Issue Addressed: Problem-based learning (PBL) is a student-directed pedagogy that promotes critical thinking, self-directed learning and communication skills essential for health promotion students and practitioners. This paper reports on student results, student evaluation and staff experience of PBL in the face-to-face and fully online environment in an undergraduate health sciences unit in an Australian university., Methods: A single time-point study using quantitative and qualitative administrative student data (2014-2020) and narrative reflection from teaching academics (n = 5) was undertaken. Descriptive, independent t test and bivariate analyses for student results data were conducted; an inductive approach was used to analyse qualitative data and create codes., Results: Student sample (n = 472) consisted face-to-face (n = 358, 75.8%) and online (n = 114, 24.2%) enrolments. Final Unit Mark was significantly higher for fully online students compared with face-to-face students in 2018 (P = .007) and 2019 (P = .001). Final Unit Achievement was significantly higher for fully online students compared with face-to-face students in 2018 (P = .017) and 2019 (P = .043). Three themes emerged: The PBL approach; Evolution of PBLs; Student skills and competencies., Discussion: PBL allows students to learn through facilitated problem solving and strong collaborative skills. The face-to-face and fully online PBLs improved the student and academic staff experience, while supporting the development of critical thinking and self-directed research. Further, it supported students to develop their core health promotion competencies; and enhanced the online student learning experience. SO WHAT?: Vital for contemporary, global graduates, the fully online PBL approach allows students to build critical academic and professional skills utilising current information technology relevant for collaborative professional practice., (© 2022 The Authors. Health Promotion Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of Australian Health Promotion Association.)

Introduction: Despite the established finding that migrants are at higher risk of developing a first-episode psychosis, they are under-represented in cohorts of young people identified as being at ultra-high risk for psychosis (UHR). Therefore, in order to determine the reasons for these conflicting findings, this study examined the pathways to care and clinical presentation of migrants attending an At-Risk Mental State clinic., Methodology: This study included consecutive UHR cases identified over five years attending the PACE clinic in Melbourne, Australia. The CAARMS was used to assess the severity of attenuated psychotic symptoms. Depressive symptoms and functioning were measured using the PHQ9 and GAF, respectively., Results: Over the five-year study period, 461 UHR young people attended the PACE clinic and 13.7% were first-generation migrants. A higher proportion of migrants were referred by community health services, such as general practitioners, than other referral sources. Australian born UHR patients were more likely to be referred via another mental health service. There was no difference in the type or severity of attenuated psychotic symptoms based on migrant status, except that there was a trend for young African migrants to have more severe unusual thought content. Depressive symptoms and poor functioning were highly prevalent across the total cohort and did not differ according to migrant status., Conclusions: It is not yet understood why migrants are under-represented in UHR cohorts. Qualitative interviews of migrants, who are not typically identified in the UHR stage, could provide insights into the barriers to accessing care., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: In the 1990s criteria were developed to detect individuals at high and imminent risk of developing a psychotic disorder. These are known as the at risk mental state, ultra high risk or clinical high risk criteria. Individuals meeting these criteria are symptomatic and help-seeking. Services for such individuals are now found worldwide. Recently Psychological Medicine published two articles that criticise these services and suggest that they should be dismantled or restructured. One paper also provides recommendations on how ARMS services should be operate., Methods: In this paper we draw on the existing literature in the field and present the perspective of some ARMS clinicians and researchers., Results: Many of the critics' arguments are refuted. Most of the recommendations included in the Moritz et al. paper are already occurring., Conclusions: ARMS services provide management of current problems, treatment to reduce risk of onset of psychotic disorder and monitoring of mental state, including attenuated psychotic symptoms. These symptoms are associated with a range of poor outcomes. It is important to assess them and track their trajectory over time. A new approach to detection of ARMS individuals can be considered that harnesses broad youth mental health services, such as headspace in Australia, Jigsaw in Ireland and ACCESS Open Minds in Canada. Attention should also be paid to the physical health of ARMS individuals. Far from needing to be dismantled we feel that the ARMS approach has much to offer to improve the health of young people.

Background: Certain migrant groups are more likely to develop a psychotic disorder compared to the native-born populations, and a younger age at migration is associated with greater risk. However, it is not known at which stage migration has an effect on the development of psychotic disorders. We examined whether migrants were more likely to be identified as ultra-high risk for psychosis (UHR) compared to native-born young people and whether migrant status was associated with the risk of transition to a full-threshold psychotic disorder., Methods: The cohort included all young people aged 15-24 who were identified as UHR at a specialist clinic over a five-year period (2012-16). Australian census data were used to obtain the at-risk population. Poisson regression was used to calculate rate ratios and Cox regression analysis determined hazard ratios., Results: 467 young people were identified as UHR, of which 13.5% (n = 63) were born overseas. First-generation migrants were 2.6-fold less likely to be identified as UHR compared to Australian-born young people (IRR = 0.39, 95% CI [0.30, 0.51], P < 0.001). There was no difference between migrant and native-born young people in their risk of transitioning to a psychotic disorder (HR = 0.90, 95% CI [0.39, 2.08], P = 0.81)., Conclusions: UHR first-generation migrants may be under-accessing mental health services., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: Up to half of patients with borderline personality disorder report auditory verbal hallucinations that are phenomenologically indistinguishable from those in schizophrenia, occur early in the course of the disorder, and are enduring, distressing and disabling. In clinical practice, this symptom is widely assumed to be unresponsive to treatment with antipsychotic medication and early intervention is rarely offered. The Verbal Experiences Response in Borderline personality disorder to Aripiprazole TrIal Medication (VERBATIM) study aims to be the first controlled trial to investigate the effectiveness of conventional pharmacotherapy for this symptom in this patient group., Method: VERBATIM is a 12-week, triple-blind, single-centre, parallel groups randomised controlled trial, with a 27-week follow-up period. Participants between the ages of 15 and 25 years receive either aripiprazole or placebo daily, commencing at 2 mg and increasing to 10 mg by day 15. Further dose escalations (up to 30 mg) may occur, as clinically indicated. This trial was prospectively registered with the Australian and New Zealand Clinical Trials Registry ACTRN12616001192471 on 30/08/2016., Results: The primary outcome is severity of auditory verbal hallucinations assessed using the Psychotic Symptom Rating Scale. Secondary outcomes include the severity of general psychopathology, borderline personality pathology, social and occupational functioning and change in brain resting state connectivity. The primary endpoint is week 12 and secondary endpoint is week 39., Conclusion: The results will inform treatment decisions for individuals with borderline personality disorder who present with auditory verbal hallucinations., (© 2019 John Wiley & Sons Australia, Ltd.)

Decreased brain activity in the frontal region, as indicated by increased slow wave EEG power measured by electrodes place on the skull over this area, in association with negative symptoms has previously been shown to distinguish ultra-high risk (UHR) individuals who later transitioned to psychosis (UHR-P) from those who did not transition (UHR-NP). The aims of the current study were to: 1) replicate these results and 2) investigate whether similar association between increased frontal slow wave activity and functioning shows any value in the prediction of transition to psychosis in UHR individuals. The brain activity, recorded using EEG, of 44 UHR individuals and 38 healthy controls was included in the analyses. Symptom severity was assessed in UHR participants and functioning was measured in both groups. The power in the theta frequency band in the frontal region of UHR individuals was higher than in controls. However, there was no difference between the UHR-P and the UHR-NP groups, and no change in slow frequency power following transition to psychosis. The correlation between delta frequency power and negative symptoms previously observed was not present in our UHR cohort, and there was no association between frontal delta or theta and functioning in either group. Increased delta power was rather correlated with depressive symptoms in the UHR group. Future research will be needed to better understand when, in the course of the illness, does the slow wave activity in the frontal area becomes impaired., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aim: On the basis of applying 'ultra-high-risk' (UHR) criteria, initially high rates of transition to psychosis were reported. However, a decline in transition to psychosis has been observed in recent years. The current descriptive paper aims to investigate if this drop in transition rate may be due to potential changes in patterns of referral to a large UHR clinic., Methods: One hundred fifty young people who were referred to the Personal Assessment and Crisis Evaluation (PACE) Clinic in Melbourne, Australia, between August 2000 and July 2004 were included. Their referral pathways were assessed using a semistructured interview. Results were compared with a similar study of a cohort referred to the same clinic between 1995 and 1996., Results: The mean number of contacts prior to referral to the PACE Clinic was 1.93 (standard deviation (SD) = 1.15), and the average time between symptom onset and referral to PACE was 46.5 weeks (SD = 57.4). In comparison with the earlier cohort (mean = 2.36; SD = 1.32), our results indicate a lower number of contacts (Cohen's d = 0.35, r = 0.17). Furthermore, participants in the current study were referred twice as fast to the PACE Clinic., Conclusions: Increasing awareness of UHR symptoms among professionals and in the general population seems to have resulted in faster referral of young people to specialized mental health services. The global drop in transition rate might be due to a change in referral pathways to UHR services., (© 2013 Wiley Publishing Asia Pty Ltd.)

Objective: Two-thirds of individuals identified as at ultra-high risk for psychosis do not develop psychotic disorder over the medium term. The authors examined outcomes in a group of such patients., Method: Participants were help-seeking individuals identified as being at ultra-high risk for psychosis 2-14 years previously. The 226 participants (125 female, 101 male) completed a follow-up assessment and had not developed psychosis. Their mean age at follow-up was 25.5 years (SD=4.8)., Results: At follow-up, 28% of the participants reported attenuated psychotic symptoms. Over the follow-up period, 68% experienced nonpsychotic disorders: mood disorder in 49%, anxiety disorder in 35%, and substance use disorder in 29%. For the majority (90%), nonpsychotic disorder was present at baseline, and it persisted for 52% of them. During follow-up, 26% of the cohort had remission of a disorder, but 38% developed a new disorder. Only 7% did not experience any disorder at baseline or during follow up. The incidence of nonpsychotic disorder was associated with more negative symptoms at baseline. Female participants experienced higher rates of persistent or recurrent disorder. Meeting criteria for brief limited intermittent psychotic symptoms at intake was associated with lower risk for persistent or recurrent disorder., Conclusions: Individuals at ultra-high risk for psychosis who do not transition to psychosis are at significant risk for continued attenuated psychotic symptoms, persistent or recurrent disorders, and incident disorders. Findings have implications for ongoing clinical care.

Objectives: There are no established tools to identify individuals at risk for developing bipolar disorder. We developed a set of ultra-high-risk criteria for bipolar disorder [bipolar at-risk (BAR)]. The primary aim of the present study was to determine the predictive validity of the BAR criteria., Methods: This was a 12-month prospective study that was conducted at Orygen Youth Health Clinical Program, a public mental health program for young people aged 15-24 years in metropolitan Melbourne, Australia. At intake, BAR screen-positive individuals and a matched group of individuals who did not meet BAR criteria were observed over a period of 12 months. The BAR criteria include general criteria such as being in the peak age range for the onset of the disorder, as well as sub-threshold mania, depression plus cyclothymic features, and depression plus genetic risk. Conversion to first-episode mania/hypomania was defined by the presence of DSM-IV manic symptoms for more than four days, in line with the DSM-IV definition of hypomania/mania., Results: A total of 559 help-seeking patients were screened. Of the eligible participants, 59 (10.6%) met BAR criteria. Thirty-five participants were included in the BAR group and 35 matched participants were selected to be in the control group. During the follow-up, five BAR patients out of 35 (14.3%) converted to first-episode hypomania/mania as opposed to none in the non-BAR group [χ(2) (1) = 5.38, p = 0.020]. Four out of these five converters had a DSM-IV diagnosis of bipolar I or bipolar II disorder., Conclusions: These findings support the possibility of identification of persons prior to the onset of mania/hypomania. The proposed criteria need further evaluation in larger, prospective studies with longer follow-up periods., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Importance: The ultra high-risk (UHR) criteria were introduced to prospectively identify patients at high risk of psychotic disorder. Although the short-term outcome of UHR patients has been well researched, the long-term outcome is not known., Objective: To assess the rate and baseline predictors of transition to psychotic disorder in UHR patients up to 15 years after study entry., Design: Follow-up study of a cohort of UHR patients recruited to participate in research studies between 1993 and 2006., Setting: The Personal Assessment and Crisis Evaluation (PACE) clinic, a specialized service for UHR patients in Melbourne, Australia., Participants: Four hundred sixteen UHR patients previously seen at the PACE clinic., Main Outcomes and Measures: Transition to psychotic disorder, as measured using the Comprehensive Assessment of At-Risk Mental States, Brief Psychiatric Rating Scale/Comprehensive Assessment of Symptoms and History, or state public mental health records., Results: During the time to follow-up (2.4-14.9 years after presentation), 114 of the 416 participants were known to have developed a psychotic disorder. The highest risk for transition was within the first 2 years of entry into the service, but individuals continued to be at risk up to 10 years after initial referral. The overall rate of transition was estimated to be 34.9% over a 10-year period (95% CI, 28.7%-40.6%). Factors associated with transition included year of entry into the clinic, duration of symptoms before clinic entry, baseline functioning, negative symptoms, and disorders of thought content., Conclusions and Relevance: The UHR patients are at long-term risk for psychotic disorder, with the highest risk in the first 2 years. Services should aim to follow up patients for at least this period, with the possibility to return for care after this time. Individuals with a long duration of symptoms and poor functioning at the time of referral may need closer monitoring. Interventions to improve functioning and detect help-seeking UHR patients earlier also may be indicated.

Aims: The study aims to identify markers of vulnerability to obsessive-compulsive disorder (OCD) in an ultra-high risk sample of patients who developed psychosis., Methods: Three hundred and eleven patients at ultra-high risk for psychosis were examined at baseline and after a mean of 7.4 years follow-up. Patients who developed psychosis with OCD (PSY + OCD; n = 13) and psychosis without OCD (PSY - OCD; n = 45) were compared in terms of socio-demographic and clinical features., Results: PSY + OCD patients displayed greater severity of depression before and after conversion to PSY + OCD, and increased rates of depressive disorders before exhibiting PSY + OCD. However, they only displayed greater severity of anxiety and increased rates of non-OCD anxiety disorders after psychosis. Further, PSY + OCD patients were more likely to report a positive family history for anxiety disorders than PSY - OCD., Conclusion: Although depression and a family history of anxiety disorder may act as vulnerability markers for OCD in psychosis, the resulting anxiety may be a correlate or a consequence of PSY + OCD., (© 2012 Blackwell Publishing Asia Pty Ltd.)

Purpose: To determine if important geographic differences exist in treatment rates for osteoporosis and whether this variation can be explained by regional variation in risk factors., Methods: The Global Longitudinal Study of Osteoporosis in Women is an observational study of women ≥55 years sampled from primary care practices in 10 countries. Self-administered questionnaires were used to collect data on patient characteristics, risk factors for fracture, previous fractures, anti-osteoporosis medication, and health status., Results: Among 58,009 women, current anti-osteoporosis medication use was lowest in Northern Europe (16%) and highest in U.S.A. and Australia (32%). Between 48% (U.S.A., Southern Europe) and 68% (Northern Europe) of women aged ≥65 years with a history of spine or hip fracture since age 45 were untreated. Among women with osteoporosis, the percentage of treated cases was lowest in Europe (45-52% versus 62-65% elsewhere). Women with osteopenia and no other risk factors were treated with anti-osteoporosis medication most frequently in U.S.A. (31%) and Canada (31%), and least frequently in Southern Europe (12%), Northern Europe (13%), and Australia (16%). After adjusting for risk factors, U.S. women were threefold as likely to be treated with anti-osteoporosis medication as Northern European women (odds ratio 2.8; 95% confidence interval 2.5-3.1) and 1.5 times as likely to be treated as Southern European women (1.5, 1.4-1.6). Up to half of women reporting previous hip or spine fracture did not receive treatment., Conclusions: The likelihood of being treated for osteoporosis differed between regions, and cannot be explained by variation in risk factors. Many women at risk of fracture do not receive prophylaxis., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: Determine the effect of raloxifene or estrogen, as compared with placebo, on the reporting of urinary incontinence in postmenopausal women participating in an osteoporosis prevention trial., Design: The current analysis is based on adverse event data that were collected as part of a double-blind, randomized, placebo-controlled trial designed to assess the efficacy and safety of raloxifene for osteoporosis prevention in postmenopausal women. Women were 40 to 60 years of age at study entry and had a prior hysterectomy. A total of 619 women were randomized to placebo, raloxifene 60 or 150 mg/d, or conjugated equine estrogen 0.625 mg/d and followed for up to 3 years. Urinary incontinence was self-reported and rated by participants as "mild," "moderate," or "severe.", Results: The prevalence of urinary incontinence as reported by patients at baseline was similar across treatment groups (3% to 6%, P = 0.46). During 3 years of follow-up, new or worsening urinary incontinence was reported with the following frequency: placebo (1.3%), raloxifene 60 mg/d (0.7%), raloxifene 150 mg/d (0.6%), and conjugated equine estrogen (7.0%). The percentage of estrogen subjects reporting urinary incontinence was significantly greater than that for placebo and both doses of raloxifene (P < or = 0.02)., Conclusion: During 3 years of follow-up, conjugated equine estrogen was associated with an increased incidence of reports of urinary incontinence in women with a prior hysterectomy and this was significantly greater than both placebo and raloxifene.

Snake envenomation is a major cause of death and disability in the developing countries, particularly India and Southeast Asia. Species variation in venom components, yield, and lethality leads to quite different clinical presentations and mortality. Venomous snakes are divided into 5 families. Bites of the Viperidae, Crotalidae and Colubridae usually cause primarily local effects and bleeding; the Elapidae most commonly cause neurological symptoms, particularly paralysis; while the Hydrophidae cause paralysis and myolysis. Venoms are complex mixtures of enzymes, peptides and metalloproteins. 26 enzymes have been identified, and 10 of those are found in most venoms. Components have been identified that act as procoagulants, anticoagulants, hyaluronidases, RNases, DNases, postsynaptic toxins and presynaptic toxins. Other peptides induce capillary leak syndrome, haemolysis and shock. The clinical results of envenomation vary widely, and there may be no envenomation with a bite. Syndromes reported include oedema, haemolysis, shock, bleeding, pituitary failure, renal failure, myonecrosis, and combinations of the above. First aid measures that have been proposed include tourniquets, constricting bands, tight crepe bandages, incision and suction, cryotherapy, and high voltage electric shock. None of these has been shown to be effective except usage of a crepe bandage for Australian elapid bite. Tourniquets or cryotherapy, if used for extended periods may lead to gangrene. The most important first aid measure is rapid transport to comprehensive medical care. There is some controversy about medical treatment in the United States, but less in other countries. Supportive measures routinely required include intravenous fluids, tetanus prophylaxis and antibiotics. Anticholinergics may be useful in elapid bite. Intubation and ventilation may be necessary. Unproven surgical approaches include excision of envenomated tissues and fasciotomy. The former is disfiguring, the latter should be reserved for those patients with demonstrated increased intracompartmental pressure. More than 100 antivenins are produced by about 36 laboratories worldwide. The products are effective, but carry a high risk of serum sickness and a lesser risk of anaphylaxis. A more effective and less reactive product is under development.