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BACKGROUND AND OBJECTIVES: Membranoproliferative GN and C3 glomerulopathy are rare and overlapping disorders associated with dysregulation of the alternative complement pathway. Specific etiologic data for pediatric membranoproliferative GN/C3 glomerulopathy are lacking, and outcome data are based on retrospective studies without etiologic data. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A total of 80 prevalent pediatric patients with membranoproliferative GN/C3 glomerulopathy underwent detailed phenotyping and long-term follow-up within the National Registry of Rare Kidney Diseases (RaDaR). Risk factors for kidney survival were determined using a Cox proportional hazards model. Kidney and transplant graft survival was determined using the Kaplan–Meier method. RESULTS: Central histology review determined 39 patients with C3 glomerulopathy, 31 with immune-complex membranoproliferative GN, and ten with immune-complex GN. Patients were aged 2–15 (median, 9; interquartile range, 7–11) years. Median complement C3 and C4 levels were 0.31 g/L and 0.14 g/L, respectively; acquired (anticomplement autoantibodies) or genetic alternative pathway abnormalities were detected in 46% and 9% of patients, respectively, across all groups, including those with immune-complex GN. Median follow-up was 5.18 (interquartile range, 2.13–8.08) years. Eleven patients (14%) progressed to kidney failure, with nine transplants performed in eight patients, two of which failed due to recurrent disease. Presence of >50% crescents on the initial biopsy specimen was the sole variable associated with kidney failure in multivariable analysis (hazard ratio, 6.2; 95% confidence interval, 1.05 to 36.6; P50% crescents on the initial biopsy specimen. CONCLUSIONS: Crescentic disease was a key risk factor associated with kidney failure in a national cohort of pediatric patients with membranoproliferative GN/C3 glomerulopathy and immune-complex GN. Presenting eGFR and crescentic disease help define prognostic groups in pediatric C3 glomerulopathy. Acquired abnormalities of the alternative pathway were commonly identified but not a risk factor for kidney failure.

For most treatment-seeking patients with severe Alcohol Use Disorder (AUD), abstinence is the clinically indicated goal. Existing AUD motivation scales are non-specific about treatment consumption goals, which limit their effectiveness. Desires and mental imagery are relevant in the motivation for AUD treatment engagement. The Motivational Thought Frequency Scale for an abstinence goal (MTF-A) was adapted from the MTF for controlled drinking (MTF-CD). This study psychometrically evaluated the MTF-A in an alcohol-dependent sample engaged in treatment with a goal of abstinence. To enhance the clinical utility of the scale, a secondary aim was to evaluate a psychometrically equivalent short version of the MTF-A.A sample N of 329 treatment-seeking patients with AUD (mean age of 44.44 years, SD = 11.89 years, 72% male) who were undertaking a cognitive behavioral treatment (CBT) program for abstinence completed the Motivational Thought Frequency Scale for Abstinence (MTF-A) and the Severity of Alcohol Dependence Questionnaire (SADQ). The MTF-A measured motivation for abstinence through four factors: intensity, self-efficacy imagery, incentives imagery, and availability. Confirmatory factor analyses (CFAs) were conducted to examine factor structure and model fit. Cronbach's alpha assessed internal consistency. Predictive validity was determined by logistic regression predicting first-session treatment non-attendance and alcohol consumption between baseline assessment and commencement of treatment, controlling for potential confounds.A four-factor structure provided the best fit for the MTF-A, compared with one- and three-factor models. A shortened 9-item MTF-A scale (S-MTF-A) provided better fit than the 13-item MTF-A scale. Both MTF-A and S-MTF-A displayed good internal consistency. Although both MTF-A and S-MTF-A successfully predicted first-session treatment non-attendance, neither predicted alcohol consumption between the baseline assessment and commencement of treatment.The model fit of the four-factor, 9-item S-MTF-A was superior to the original 13-item MTF-A. Both scales were predictive of participation of AUD treatment. Desires and mental imagery play an important role in AUD treatment motivation.

Background End stage kidney disease (ESKD) is associated with many losses, subsequently impacting mental wellbeing. Few studies have investigated the efficacy of psychosocial interventions for people with ESKD and none exist for Indigenous people, a population in which the ESKD burden is especially high. Methods This three-arm, waitlist, single-blind randomised controlled trial examined efficacy of the Stay Strong App in improving psychological distress (Kessler distress scale; K10), depressive symptoms (adapted Patient Health Questionnaire; PHQ-9), quality of life (EuroQoL; EQ. 5D) and dialysis adherence among Indigenous Australians undergoing haemodialysis in central and northern Australia (Alice Springs and Darwin), with follow up over two 3-month periods. Effects of immediate AIMhi Stay Strong App treatment were compared with those from a contact control app (The Hep B Story) and treatment as usual (TAU). Control conditions received the Stay Strong intervention after 3 months. Results Primary analyses of the full sample (N = 156) showed statistically significant decreases in K10 and PHQ-9 scores at 3 months for the Hep B Story but not for the Stay Strong app or TAU. Restricting the sample to those with moderate to severe symptoms of distress or depression (K10 > =25 or PHQ-9 > =10) showed significant decreases in K10 and PHQ-9 scores for both Stay Strong and Hep B Story. No significant differences were observed for the EQ-5D or dialysis attendance. Conclusions Findings suggest that talking to people about their wellbeing and providing information relevant to kidney health using culturally adapted, locally relevant apps improve the wellbeing of people on dialysis. Further research is required to replicate these findings and identify active intervention components. Trial registration ACTRN12617000249358; 17/02/2017.

Age‐related macular degeneration (AMD) is a multifactorial disease, which is characterized by loss of central vision, affecting one in three people by the age of 75. The Y402H polymorphism in the complement factor H (CFH) gene significantly increases the risk of AMD. We show that Y402H‐AMD‐patient‐specific retinal pigment epithelium (RPE) cells are characterized by a significant reduction in the number of melanosomes, an increased number of swollen lysosome‐like‐vesicles with fragile membranes, Cathepsin D leakage into drusen‐like deposits and reduced lysosomal function. The turnover of C3 is increased significantly in high‐risk RPE cells, resulting in higher internalization and deposition of the terminal complement complex C5b‐9 at the lysosomes. Inhibition of C3 processing via the compstatin analogue Cp40 reverses the disease phenotypes by relieving the lysosomes of their overburden and restoring their function. These findings suggest that modulation of the complement system represents a useful therapeutic approach for AMD patients associated with complement dysregulation., Schematic presentation of autophagy‐lysosomal pathway dysfunction in Y402H‐AMD RPE cells and the impact of Cp40 in restoring the lysosomal function.

Background New parents face increased risks of emotional distress and relationship dissatisfaction. Digital interventions increase support access, but few preventive programs are optimized for both parents. Objective This study aims to conduct the first randomized controlled trial on universal self-guided digital programs to support positive perinatal adjustment of both mothers and fathers. Effects of childcare information (Baby Care) and information plus an interactive program (Baby Steps Wellbeing) were compared from the third trimester baseline to 3 and 6 months subsequently. Methods The study recruited 388 co-parenting male-female adult couples expecting their first single child (26-38 weeks’ gestation), using web-based registration. Most (337/388, 86.8%) were obtained from prenatal hospital classes. Couples’ randomization was automated and stratified by Edinburgh Postnatal Depression Scale (EPDS) scores (50% couples scored high if either mother >7, father >5). All assessments were web-based self-reports: the EPDS and psychosocial quality of life were primary outcomes; relationship satisfaction, social support, and self-efficacy for parenting and support provision were secondary. Linear mixed models provided intention-to-treat analyses, with linear and quadratic effects for time and random intercepts for participants and couples. Results Selection criteria were met by 63.9% (248/388) of couples, who were all randomized. Most participants were married (400/496, 80.6%), tertiary educated (324/496, 65.3%), employed full time (407/496, 82%), and born in Australia (337/496, 67.9%). Their mean age was 32.2 years, and average gestation was 30.8 weeks. Using an EPDS cutoff score of 13, 6.9% (18/248) of men, and 16.1% (40/248) of women screened positive for depression at some time during the 6 months. Retention of both partners was 80.6% (201/248) at the 6-month assessments, and satisfaction with both programs was strong (92% ≥50). Only 37.3% (185/496) of participants accessed their program more than once, with higher rates for mothers (133/248, 53.6%) than fathers (52/248, 20.9%; P Conclusions Three secondary outcomes showed differential benefits from Baby Steps Wellbeing, but for one (parenting self-efficacy), the effect only occurred for mothers, perhaps reflecting their greater program use. Increased engagement will be needed for more definitive testing of the potential benefits of Baby StepsWellbeing for perinatal adjustment. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12614001256662; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=367277

Introduction and Aims: Many young people engage in risky partying behaviours and excessive alcohol use in the transition period following high school graduation. Despite this, there is limited longitudinal research on adolescents before and after school graduation; and limited evaluation of interventions targeting these high-risk periods. The present study aims to address this gap in the literature by examining the impact of brief psychoeducation interventions on substance use, psychological distress and well-being during this important life transition. Design and Methods: Participants were 334 high school leavers (53% female, M = 17.14) from Queensland, Australia. They received either: (i) a psychoeducation intervention on safe partying behaviours; (ii) a reconstructed version of the psychoeducation intervention; or (iii) a standard health curriculum control. Surveys were conducted at baseline; 2 weeks, immediately following post-graduation celebratory event ‘Schoolies’; and 4 months, immediately following university orientation ‘O-week’. Results: Significant time by group effects were found for problem drinking, F(2, 227) = 3.07, P < 0.05, and well-being, F(4, 439) = 3.54, P < 0.01. There was stability in problem drinking from baseline to follow-up for the psychoeducation groups but small increases in problem drinking for the control (d = 0.12). Both psychoeducation groups had improvements in well-being scores from baseline to post-Schoolies (d = 0.40; 0.20), which were maintained across time. In contrast, the control condition showed a decrease in well-being scores from baseline to the post O-week follow-up (d = 0.15). Discussion and Conclusions: Brief school-based psychoeducational interventions may result in small improvements in well-being, and possibly stabilise the trajectory of problematic drinking in high-risk environments.

Incidence of end stage kidney disease (ESKD) for Indigenous Australians is especially high in remote and very remote areas of Australia (18 and 20 times the rate of comparable non-Indigenous people). Relocating away from family and country for treatment, adjusting to life with a chronic condition and time lost to dialysis cause grief and sadness which have immense impact on quality of life and challenges treatment adherence. We describe the first randomised controlled trial to address both chronic disease and mental health in Indigenous people with ESKD, which is the first to test the effectiveness of a culturally adapted e-mental health intervention in this population. It builds on an existing program of mental health research with demonstrated efficacy – the Aboriginal and Islander Mental Health Initiative (AIMhi) – to test the newly developed electronic motivational care planning (MCP) therapy – the AIMhi Stay Strong App. This is a 3-arm, waitlist, single-blind randomised controlled trial testing the efficacy of the Stay Strong App in improving psychological distress, depressive symptoms, quality of life and treatment adherence among Indigenous clients undergoing haemodialysis for ESKD in Alice Springs and Darwin with follow up over two periods of 3 months (total of 6 months observation). The study compares the efficacy of MCP using the AIMhi Stay Strong App with two control groups (control app intervention and treatment as usual) on participant-reported psychological distress (the primary outcome) using the Kessler Distress Scale (K10); depressive symptoms using the adapted Patient Health Questionnaire (PHQ-9); quality of life using the EuroQoL instrument (EQ5D) and adherence to dialysis treatment planning through file audit. Participants are randomised to receive MCP either at baseline (early treatment) or after 3 months (delayed treatment). The study also examines the cost effectiveness of this therapy in this setting through examination of health care service utilisation across groups during the first 3 months. This project will contribute much needed evidence on the efficacy of an electronic wellbeing intervention for Indigenous people with ESKD – a group in which distress is likely to be unacceptably high, yet relatively untreated. Australian New Zealand Clinical Trial Registry; ACTRN12617000249358 ; Date registered: 17/02/2017.

Background and aims Negative affect and alcohol craving are common features of Alcohol Use Disorder (AUD). Both independently contribute to AUD severity and poorer treatment outcomes, but their relationship is poorly understood. Multidimensional alcohol craving measures now allow for examination of key dimensions of craving. This study explored the relationship between depression, anxiety, stress, and the alcohol craving dimensions of intensity, imagery and intrusiveness. Method Five-hundred and twenty-five treatment seeking AUD patients (mean age of 39.79 years, SD = 11.57 years, 67% male) completed the Depression Anxiety Stress Scales (DASS), Alcohol Use Disorder Identification Test-Consumption items (AUDIT-C), and Alcohol Craving Experience (ACE-F) questionnaire, which measured the frequency of craving intensity, imagery and intrusiveness. Regression models predicted main effects of predictors and moderation by alcohol consumption. Results Higher levels of stress were independently associated with increased craving intensity, imagery and intrusiveness. Significant positive associations were also found between anxiety and craving imagery. The association between depression and craving was not significant after controlling for other predictors. Conclusions AUD patients experienced higher cravings when stressed and greater imagery when anxious. These results support the need to consider the relationships between stress and craving when managing alcohol dependence.

Objectives: Sexual minority young people (SMYP) show higher levels of substance use than their heterosexual counterparts. This study aims to test potential LGBT community‐specific reasons assumed to affect substance use and their relationships to LGBT community participation/connectedness and substance use behaviour. Methods: Eight LGBT community‐specific reasons for substance use were tested in an online survey with 1,556 SMYP. Results: Respondents agreed that the LGBT community had liberal attitudes towards substance use (80.5%, n=1,079) and that the media portrayed substance use as a part of the community culture (66.5%, n=904). Participants disagreed that excessive partying is a part of the community (34.7%, n=470). Significant but weak correlations between reasons and community participation/connectedness or personal substance use behaviour were found. Subgroup analyses indicated male and gay/lesbian participants showed differential agreement levels to some of the reasons. Conclusion: Young people’s perceptions of substance use within the LGBT community are not associated with community participation/connectedness or personal substance use. Implications for public health: Further research is needed to better understand what factors lead to elevated levels of substance use in SMYP. This may assist in the development of adequate public health responses. Targeting problematic beliefs may have little impact on substance use in SMYP.

Background Chronic kidney disease is an increasingly common health problem for Aboriginal and Torres Strait Islander people. It is associated with multiple concurrent psychosocial stressors frequently resulting in negative impacts on emotional and social wellbeing. There is need for well-designed intervention studies to provide evidence of effective treatment for comorbid depression or other mental illness in this setting. Attention to early phase piloting and development work is recommended when testing complex interventions. This paper documents feasibility testing and adaptation of an existing culturally responsive brief wellbeing intervention, the Stay Strong App, and three commonly used wellbeing outcome measures, in preparation for a clinical trial testing effectiveness of the intervention. Methods The Stay Strong App, which has not been used in the setting of Chronic Kidney Disease before, is reviewed and adapted for people with comorbid wellbeing concerns through expert consensus between research team and an Expert Panel. The outcome measures (Kessler 10, Patient Health Questionnaire 9, and EuroQoL) are valid, reliable, and commonly used tools to assess various aspects of wellbeing, which have also not been used in this context before. Feasibility and acceptability are examined and developed through 3 stages: Pilot testing in a purposive sample of five haemodialysis patients and carers; translation of outcome measures through collaboration between the Aboriginal Interpreter Service, Aboriginal and Torres Strait Islander research officers and the research team; and conversion of translated outcome measures to electronic format. Results Research team and expert panel consensus led to adaptation of the Stay Strong App for renal patients through selective revision of words and images. Pilot testing identified challenges in delivery of the wellbeing measures leading to word changes and additional prompts, integration of audio translations in 11 local Indigenous languages within an interactive Outcome Measures App, and related research protocol changes. Conclusion Modelling the complex intervention prior to full-scale testing provided important information about the design of both the outcome measures and the intervention. These changes are likely to better support success in conduct of the clinical trial and future implementation of the intervention in clinical settings.

Background PTSD Coach Australia is an app for serving and ex-serving defense members and was adapted for the Australian context in 2013 from PTSD Coach, which was created in the United States. Objective This study aimed to provide a user-centered evaluation of the app from the perspective of serving and ex-serving members of the Australian Defence Force. Methods Qualitative data were collected in response to questions to participants in 1 of 5 workshops (n=29) or in telephone interviews (n=24). Quantitative data were collected using the user version of Mobile Apps Rating Scale (uMARS). Results Analysis of the qualitative data demonstrated mixed support for the app. While some people found it extremely useful, especially as an adjunct to therapy, others pointed out limitations and cautioned against the app potentially triggering symptoms in people with PTSD. This perceived risk was usually found to stem from frustration with the app’s functionality rather than its content. Participants spoke about the helpful and unhelpful aspects of the app and barriers to its use and made suggestions for improvement. Many participants encouraged its continued use and highlighted the need for it to be promoted more broadly, as many were not aware of it until they were invited to participate in this research. Conclusions PTSD Coach Australia was seen in a positive light by some participants, but others thought it had too much text and the potential to trigger a traumatic response in users with PTSD. A need to update the app was also a common comment as was the need to increase awareness of the app’s existence.

Background: Interest is growing in digital and telehealth delivery of mental health services, but data are scarce on outcomes in routine care. The federally funded Australian MindSpot Clinic provides online and telephone psychological assessment and treatment services to Australian adults. We aimed to summarise demographic characteristics and treatment outcomes of patients registered with MindSpot over the first 7 years of clinic operation. Methods: We used an observational design to review all patients who registered for assessment with the MindSpot Clinic between Jan 1, 2013, and Dec 31, 2019. We descriptively analysed the demographics, service preferences, and baseline symptoms of patients. Among patients enrolled in a digital treatment course, we evaluated scales of depression (Patient Health Questionnaire-9 [PHQ-9]) and anxiety (Generalized Anxiety Disorder 7-Item Scale [GAD-7]), as primary measures of treatment outcome, from the screening assessment to post-treatment and a 3 month follow-up. The Kessler Psychological Distress 10-Item Plus Scale was also used to assess changes in general distress and disability, and course satisfaction was measured post-treatment. Outcomes: A total of 121 652 screening assessments were started, of which 96 018 (78·9%) were completed. The mean age of patients was 35·7 years (SD 13·8) and 88 702 (72·9%) were women. Based on available assessment data, 36 866 (34·5%) of 106 811 participants had never previously spoken to a health professional about their symptoms, and most people self-reported symptoms of anxiety (88 879 [81·9%] of 108 494) or depression (78 803 [72·6%] of 108 494), either alone or in combination, at baseline. 21 745 patients started treatment in a therapist-guided online course, of whom 14 503 (66·7%) completed treatment (≥four of five lessons). Key trends in service use included an increase in the proportion of people using MindSpot primarily for assessment and information, from 52·6% in 2013 to 66·7% in 2019, while the proportion primarily seeking online treatment decreased, from 42·6% in 2013 to 26·7% in 2019. Effect sizes and percentage changes were large for estimated mean scores on the PHQ-9 and GAD-7 from assessment to post-treatment (PHQ-9, Cohen's d effect size 1·40 [95% CI 1·37-1·43]; and GAD-7, 1·45 [1·42-1·47]) and the 3 month follow-up (PHQ-9, 1·36 [1·34-1·38]; and GAD-7, 1·42 [1·40-1·44]); proportions of patients with reliable symptom deterioration (score increase of ≥6 points [PHQ-9] or ≥5 points [GAD-7]) were low post-treatment (of 13 058 respondents, 184 [1·4%] had symptom deterioration on the PHQ-9 and 282 [2·2%] on the GAD-7); and patient satisfaction rates were high (12 452 [96·6%] of 12 895 respondents would recommend the course and 12 433 [96·7%] of 12 860 reported the course worthwhile). We also observed small improvements in disability following treatment as measured by days out of role. Interpretation: Our findings indicate improvement in psychological symptoms and positive reception among patients receiving online mental health treatment. These results support the addition of digital services such as MindSpot as a component in contemporary national mental health systems. Funding: None. Funding agencies: Australian GovernmentAustralian GovernmentCGIAR

Objective: Functional Imagery Training (FIT) is a new brief motivational intervention based on the Elaborated Intrusion theory of desire. FIT trains the habitual use of personalised, affective, goal-directed mental imagery to plan behaviours, anticipate obstacles, and mentally try out solutions from previous successes. It is delivered in the client-centred style of Motivational Interviewing (MI). We tested the impact of FIT on weight loss, compared with time- and contact-matched MI. Design: We recruited 141 adults with BMI (kg/m²) ≥25, via a community newspaper, to a single-centre randomised controlled trial. Participants were allocated to one of two active interventions: FIT or MI. Primary data collection and analyses were conducted by researchers blind to interventions. All participants received two sessions of their allocated intervention; the first face-to-face (1 h), the second by phone (maximum 45 min). Booster calls of up to 15 min were provided every 2 weeks for 3 months, then once-monthly until 6 months. Maximum contact time was 4 h of individual consultation. Participants were assessed at Baseline, at the end of the intervention phase (6 months), and again 12 months post-baseline. Main outcome measures: Weight (kg) and waist circumference (WC, cm) reductions at 6 and 12 months. Results: FIT participants (N = 59) lost 4.11 kg and 7.02 cm of WC, compared to.74 kg and 2.72 cm in the MI group (N = 55) at 6 months (weight mean difference (WMD) = 3.37 kg, p

To assess gender differences in the relationship between eating and weight loss attitudes (EWAs), and 30-day tobacco and alcohol use among adolescents, while controlling for potential confounds (age, country of birth, psychological distress, pubertal development, peer alcohol and tobacco use, and sexual activity).School students aged between 11 and 17 years (N = 10,273) from high schools in the State of Victoria (Australia) completed surveys in class under conditions of anonymity and confidentiality.The interaction between EWAs and gender was significant for tobacco use but not for alcohol use, indicating that the effect of EWAs on tobacco use, but not alcohol use, vary by gender.Tobacco use was related to EWAs in adolescent females but not males, and this is consistent with the possibility that females use tobacco in an instrumental fashion to control weight. Implications and Contribution: Female adolescents high in eating and weight loss attitudes were more likely to engage in tobacco use. In contrast, eating and weight loss attitudes were not related to male tobacco use. These results point to the potential importance of developing gender-specific approaches towards addressing problematic behaviors in adolescent populations.

Mobile apps provide a highly accessible way of reducing alcohol use in young people. This paper determines the 1-month efficacy and 2, 3 and 6 month outcomes of the Ray's Night Out app, which aims to increase alcohol knowledge and reduce alcohol use in young people. User-experience design and agile development processes, informed by the Information-Motivation-Behavioral skills model and evidence-based motivational interviewing treatment approaches guided app development. A randomized controlled trial comparing immediate versus 1-month delayed access to the app was conducted in 197 young people (16 to 25 years) who drank alcohol in the previous month. Participants were assessed at baseline, 1, 2, 3 and 6 months. Alcohol knowledge, alcohol use and related harms and the severity of problematic drinking were assessed. App quality was evaluated after 1-month of app use. Participants in the immediate access group achieved a significantly greater increase in alcohol knowledge than the delayed access group at 1-month, but no differences in alcohol use or related problems were found. Both groups achieved significant reductions in the typical number of drinks on a drinking occasion over time. A reduction in maximum drinks consumed was also found at 1 month. These reductions were most likely to occur in males and problem drinkers. Reductions in alcohol-related harm were also found. The app received a high mean quality (M = 3.82/5, SD = 0.51). The Ray app provides a youth-friendly and easily-accessible way of increasing young people's alcohol knowledge but further testing is required to determine its impact on alcohol use and related problems.

A 4-year-old boy presented with nonimmune hemolysis, thrombocytopenia, and acute kidney injury. Investigations for an underlying cause failed to identify a definitive cause and a putative diagnosis of complement-mediated atypical hemolytic uremic syndrome (aHUS) was made. The patient was started initially on plasma exchange and subsequently eculizumab therapy, after which his kidney function rapidly improved. While on eculizumab therapy, despite adequate complement blockade, he presented 2 more times with hemolytic anemia and thrombocytopenia, but without renal involvement. Genetic analysis did not uncover a mutation in any known aHUS gene (CFH, CFI, CFB, C3, CD46, THBD, INF2, and DGKE) and anti-factor H antibodies were undetectable. Whole-exome sequencing was undertaken to identify a cause for the eculizumab resistance. This revealed a pathogenic variant in G6PD (glucose-6-phosphate dehydrogenase), which was confirmed by functional analysis demonstrating decreased erythrocyte G6PD activity. Eculizumab therapy was withdrawn. Complement-mediated aHUS is a diagnosis of exclusion and this case highlights the diagnostic difficulty that remains without an immediately available biomarker for confirmation. This case of G6PD deficiency presented with a phenotype clinically indistinguishable from complement-mediated aHUS. We recommend that G6PD deficiency be included in the differential diagnosis of patients presenting with aHUS and suggest measuring erythrocyte G6PD concentrations in these patients.

Background The purpose of this study was to investigate neurocognitive, demographic and clinical correlates of vocational participation among a sample of young help-seeking adults. Methods Young people (18–25 years) accessing an early intervention youth health service participated. The Global Functioning: Role scale and level of vocational participation, participant characteristics (age, gender, socioeconomic background and family history of serious mental illness), distress, psychotic-like experiences, substance use, and mental health diagnoses were recorded. The Cambridge Neuropsychological Testing Automated Battery was used to assess sustained attention, visual memory and executive function. Results Of the 107 participants, 33 (31%) were not working or studying and 52 (49%) had a diagnosis of affective disorder. Impairments in neurocognitive tests were evidenced in attention shift, sustained attention target sensitivity, impulsivity and spatial working memory errors. Univariate analyses indicated that information processing and target impulsivity were associated with both vocational participation and global functioning, and that spatial working memory strategy was also associated with vocational participation. After controlling for significant demographic and clinical predictors, strategy formation remained a significant correlate of vocational participation (coefficient (95%CI) = −0.08 (−0.17, −0.01)), but no neurocognitive measures remained significant in the multivariate prediction of global functioning. Limitations Neurocognitive outcomes were assessed at a single time point, factors such as fluctuations in motivation could impact on test results. Conclusions Interventions targeting work and education participation should consider the capacity of vulnerable young people to develop appropriate plans for role success and provide support accordingly. The study also emphasised the importance of high school completion and avoidance of cannabis use, especially in males.

Aim: This investigation aims to identify if correlates of not working or studying were also correlated with part‐time vocational participation. Methods: Demographic and vocational engagement information was collected from 226 participant clinical charts aged 15 to 25 years accessing a primary youth health clinic. Multinomial logistic regressions were used to examine potential correlates no and part‐time vocational engagement compared to those full‐time. Results: A total of 33% were not working or studying and 19% were part‐time. Not working or studying was associated with secondary school dropout and a history of drug use. These associations were not observed in those participating part‐time. Conclusions: This result suggests that the markers of disadvantage observed in those not working or studying do not carry over to those who are part‐time. Potentially, those who are part‐time are less vulnerable to long‐term disadvantage compared to their unemployed counterparts as they do not share the same indicators of disadvantage.

Objective While some studies suggest that men and women report different symptoms associated with depression, no published systematic review or meta-analysis has analyzed the relevant research literature. This article aims to review the evidence of gender differences in symptoms associated with depression. Methods PubMed, Cochrane, and PsycINFO databases, along with further identified references lists, were searched. Thirty-two studies met the inclusion criteria. They included 108,260 participants from clinical and community samples with a primary presentation of unipolar depression. All 32 studies were rated for quality and were tested for publication bias. Meta-analyses were conducted on the 26 symptoms identified across the 32 studies to assess for the effect of gender. Results The studies indicate a small, significant association of gender with some symptoms. Depressed men reported alcohol/drug misuse (Hedges's g = 0.26 [95% confidence interval (CI), 0.11-0.42]) and risk taking/poor impulse control (g = 0.58 [95% CI, 0.47-0.69]) at a greater frequency and intensity than depressed women. Depressed women reported symptoms at a higher frequency and intensity that are included as diagnostic criteria for depression such as depressed mood (g = -0.20 [95% CI, -0.33 to -0.08]), appetite disturbance/weight change (g = -0.20 [95% CI, -0.28 to -0.11]), and sleep disturbance (g = -0.11 [95% CI, -0.19 to -0.03]). Conclusions Results are consistent with existing research on gender differences in the prevalence of substance use and mood disorders, and of their co-occurrence. They highlight the potential utility of screening for substance misuse, risk taking, and poor impulse control when assessing depression in men. Future research is warranted to clarify gender-specific presentations of depression and co-occurring symptoms.

Background and Aims: Recent meta-analyses of motivational interviewing (MI) for reducing risky alcohol use in young people have reported modest effects. Few studies have targeted individual patient factors to increase MI effectiveness. This study determined if MI enhanced with individualised personality-specific coping skills training (QuikFix) was more efficacious than standard MI or an assessment feedback/information (AF/I) control among young people with alcohol-related injuries or illnesses. Design and Setting: Single-centre, single-blind, three-group superiority randomized controlled trial with 1-, 3-, 6- and 12-months follow-ups. Telephone intervention, Brisbane, Australia. Participants: A total of 398 young people (16–25 years; M age = 20.30 years, SD = 2.12; 54% female) with alcohol-related injuries and/or illnesses were recruited from an emergency department (ED) or rest/recovery service (RRS). Measures: The primary outcome was total standard (10 g ethanol) drinks in the past month (Timeline Follow back [TLFB]) at 12 months (primary time point). Secondary outcomes were total drinking days and standard drinks per drinking day (TLFB) in the past month and the frequency of alcohol-related problems in the past 3 months (Rutgers Alcohol Problem Index). Interventions: Young people were randomized to two sessions of QuikFix enhanced with individualised personality-specific coping skills training (n = 132), two sessions of MI (n = 136) or one session of AF/I (n = 130), all delivered by telehealth. Findings: QuikFix resulted in greater reductions (all P

BackgroundRestrictive practices on alcohol sales in entertainment districts have been introduced to reduce alcohol-related violence in youth. On 1st July 2016, the Queensland State Government (Australia) imposed a 2-hour reduction in trading hours for alcohol sales in venues within specific night-time entertainment districts (NEDS; from 5am to 3am), a reduction in maximum trading hours for venues outside NEDs (with a maximum 2am closing time), the banning of 'rapid intoxication drinks' (e.g. shots) after 12am, and no new approvals for trading hours beyond 10pm for the sale of takeaway alcohol. No independent study has evaluated general levels of intoxication, crowd numbers, fear of violence, and illicit substance use as people enter and exit NEDS, both before and after the introduction of restrictive legislation. Further, no study has assessed the impact using matched times of the year in a controlled study and also assessed actual assault rates as recorded by the police.MethodWe conducted 3 studies-randomly breath-testing patrons for alcohol, as they entered and exited NEDs. Study 1 assessed patrons' (n = 807) breath approximated blood alcohol concentration (BrAC) and predictions of how the legislation would change their drinking habits before the legislation was enacted. Study 2 assessed crime statistics and patrons' BrAC levels and drug taking reports on an equivalent night, one year apart-before (n = 497) and after (n = 406) the new legislation. Study 3 was a test of the generalisation of Study 2 with two months of survey and BrAC data collected as people entered and exited the NEDs over two consecutive years before (n = 652 and n = 155) and one year after (n = 460) the new legislation. In Study 3 we also collected crime statistics and data on people leaving the entertainment district one year before (n = 502) and one year after (n = 514) the legislative change.FindingsPeople predicted that the legislation would lead to them drinking more alcohol before they entered town or make little change to their drinking habits. Baseline data over the 2 years before the legislation (Study 3) demonstrated stable preloading rates and BrAC at entry to the NEDs. However, after the introduction of the legislation patrons entered the NEDs systematically later and increased their alcohol preloading. People were substantially more inebriated as they entered the NEDs after the legislative change, with approximately 50% fewer people not preloading after the new laws. Exit BrAC was less consistent but showed some evidence of an increase. Crime statistics and patrons' self-reported experiences of violence did not change.InterpretationLegislation that does not specifically adapt to the cultural shift of preloading and take local conditions into account will be unsuccessful in reducing alcohol consumption. Such legislation is unlikely to meaningfully change assault rates in youth.

There is a need for improved measurement of motivation for diabetes self-care. The Elaborated Intrusion Theory of Desire offers a coherent framework for understanding and identifying the cognitive-affective events that constitute the subjective experience of motivation and may therefore inform the development of such an instrument. Recent research has shown the resultant Motivation Thought Frequency scale (MTF) to have a stable factor structure (Intensity, Incentives Imagery, Self-Efficacy Imagery, Availability) when applied to physical activity, excessive snacking or alcohol use in the general population. The current study aimed to confirm the four-factor structure of the MTF for glucose testing, physical activity and healthy eating in people with type 2 diabetes. Associations with self-reports of concurrent diabetic self-care behaviours were also examined. Confirmatory factor analyses tested the internal structure, and multiple regressions assessed the scale’s relationship with concurrent self-care behaviours. The MTF was completed by 340 adults with type 2 diabetes, and 237 from that sample also reported self-care behaviours. Separate MTFs assessed motivation for glucose testing, physical activity and healthy eating. Self-care was assessed using questions from the Summary of Diabetes Self-Care Activities. The MTF for each goal achieved an acceptable fit on all indices after selected errors within factors were allowed to intercorrelate. Intensity and Self-Efficacy Imagery provided the strongest and most consistent correlations with relevant self-care behaviours. Results provide preliminary support for the MTF in a diabetes sample. Testing of its sensitivity to change and its predictive utility over time is needed.

Disengagement from services is common before suicide, hence identifying factors at treatment presentation that predict future suicidality is important. This article explores risk profiles for suicidal ideation among treatment seekers with depression and substance misuse. Participants completed assessments at baseline and 6 months. Baseline demographics, psychiatric history, and current symptoms were entered into a decision tree to predict suicidal ideation at follow-up. Sixty-three percent of participants at baseline and 43.5% at follow-up reported suicidal ideation. Baseline ideation most salient when psychiatric illness began before adulthood, increasing the rate of follow-up ideation by 16%. Among those without baseline ideation, dysfunctional attitudes were the most important risk factor, increasing rates of suicidal ideation by 35%. These findings provide evidence of factors beyond initial diagnoses that increase the likelihood of suicidal ideation and are worthy of clinical attention. In particular, providing suicide prevention resources to those with high dysfunctional attitudes may be beneficial.

Chromosomal rearrangements affecting the genes encoding complement factor H and the factor H related proteins have been described in aHUS patients. To date such disorders have not been described in other aHUS associated genes. We describe here a heterozygous 875,324bp deletion encompassing the gene (CFI) encoding complement factor I and ten other genes. The index case presented with aHUS and did not recover renal function. No abnormalities were detected on Sanger sequencing of CFI but a low factor I level led to a multiplex ligation-dependent probe amplification assay being undertaken. This showed a complete heterozygous deletion of CFI. The extent of the deletion and the breakpoint was defined. In the Newcastle aHUS cohort we have identified and report here 32 different CFI variants in 56 patients but to date this is the only deletion that we have identified. This finding although rare does suggest that screening for chromosomal rearrangements affecting CFI should be undertaken in all aHUS patients particularly if the factor I level is unexplainably low.

Internationally there is a growing interest in the mental wellbeing of young people. However, it is unclear whether mental wellbeing is best conceptualized as a general wellbeing factor or a multidimensional construct. This paper investigated whether mental wellbeing, measured by the Mental Health Continuum-Short Form (MHC-SF), is best represented by: (1) a single-factor general model; (2) a three-factor multidimensional model or (3) a combination of both (bifactor model). 2220 young Australians aged between 16 and 25 years completed an online survey including the MHC-SF and a range of other wellbeing and mental ill-health measures. Exploratory factor analysis supported a bifactor solution, comprised of a general wellbeing factor, and specific group factors of psychological, social and emotional wellbeing. Confirmatory factor analysis indicated that the bifactor model had a better fit than competing single and three-factor models. The MHC-SF total score was more strongly associated with other wellbeing and mental ill-health measures than the social, emotional or psychological subscale scores. Findings indicate that the mental wellbeing of young people is best conceptualized as an overarching latent construct (general wellbeing) to which emotional, social and psychological domains contribute. The MHC-SF total score is a valid and reliable measure of this general wellbeing factor.

Background: Smoking cessation interventions delivered by dental practitioners can be as effective as those delivered by general medical practitioners. However, concern that addressing smoking may cause offence to their patients is a reason cited by dental practitioners for not regularly addressing patient smoking behaviours, despite believing they should play a role in smoking cessation. This study aimed to elicit the smoking behaviour and smoking cessation preferences of dental patients to determine if these concerns accurately reflect patient attitudes. Methods: We surveyed 726 adult dental patients attending the University of Queensland’s School of Dentistry Dental Clinics, Brisbane Dental Hospital, and four private dental practices in South East Queensland. Results: Most (80%) current daily smokers had tried to quit smoking. Smokers and non-smokers both agreed that dentists should screen for smoking behaviour and are qualified to offer smoking cessation advice (99% and 96% respectively). Almost all participants (96%) said they would be comfortable with their dentist asking about their smoking and that if their smoking was affecting their oral health their dentist should advise them to quit. Conclusions: Patients are receptive to dental practitioners inquiring about smoking behaviour and offering advice on quitting. Smoking patients showed considerable motivation and interest in quitting smoking, particularly in the context of health problems related to smoking being identified. These results should encourage dentists to raise the issue with their patients.

Functional Imagery Training (FIT) is a new theory-based, manualized intervention that trains positive goal imagery. Multisensory episodic imagery of proximal personal goals is elicited and practised, to sustain motivation and compete with less functional cravings. This study tested the impact of a single session of FIT plus a booster phone call on snacking. In a stepped-wedge design, 45 participants who wanted to lose weight or reduce snacking were randomly assigned to receive a session of FIT immediately or after a 2-week delay. High-sugar and high-fat snacks were recorded using timeline follow back for the previous 3 days, at baseline, 2 and 4 weeks. At 2 weeks, snacking was lower in the immediate group than in the delayed group, and the reduction after FIT was replicated in the delayed group between 2 and 4 weeks. Frequencies of motivational thoughts about snack reduction rose following FIT for both groups, and this change correlated with reductions in snacking and weight loss. By showing that FIT can support change in eating behaviours, these findings show its potential as a motivational intervention for weight management.

BACKGROUND: Methamphetamine use can produce symptoms almost indistinguishable from schizophrenia. Distinguishing between the two conditions has been hampered by the lack of a validated symptom profile for methamphetamine-induced psychiatric symptoms. We use data from a longitudinal cohort study to examine the profile of psychiatric symptoms that are acutely exacerbated by methamphetamine use. METHODS: 164 methamphetamine users, who did not meet DSM-IV criteria for a lifetime primary psychotic disorder, were followed monthly for one year to assess the relationship between days of methamphetamine use and symptom severity on the 24-item Brief Psychiatric Rating Scale. Exacerbation of psychiatric symptoms with methamphetamine use was quantified using random coefficient models. The dimensions of symptom exacerbation were examined using principal axis factoring and a latent profile analysis. RESULTS: Symptoms exacerbated by methamphetamine loaded on three factors: positive psychotic symptoms (suspiciousness, unusual thought content, hallucinations, bizarre behavior); affective symptoms (depression, suicidality, guilt, hostility, somatic concern, self-neglect); and psychomotor symptoms (tension, excitement, distractibility, motor hyperactivity). Methamphetamine use did not significantly increase negative symptoms. Vulnerability to positive psychotic and affective symptom exacerbation was shared by 28% of participants, and this vulnerability aligned with a past year DSM-IV diagnosis of substance-induced psychosis (38% vs. 22%, χ(2)(df1)=3.66, p=0.056). CONCLUSION: Methamphetamine use produced a symptom profile comprised of positive psychotic and affective symptoms, which aligned with a diagnosis of substance-induced psychosis, with no evidence of a negative syndrome. Language: en

Expressed emotion (EE) captures the affective quality of the relationship between family caregivers and their care recipients and is known to increase the risk of poor health outcomes for caregiving dyads. Little is known about expressed emotion in the context of caregiving for persons with dementia, especially in non-Western cultures. The Family Attitude Scale (FAS) is a psychometrically sound self-reporting measure for EE. Its use in the examination of caregiving for patients with dementia has not yet been explored.This study was performed to examine the psychometric properties of the Chinese version of the FAS (FAS-C) in Chinese caregivers of relatives with dementia, and its validity in predicting severe depressive symptoms among the caregivers.The FAS was translated into Chinese using Brislin's model. Two expert panels evaluated the semantic equivalence and content validity of this Chinese version (FAS-C), respectively. A total of 123 Chinese primary caregivers of relatives with dementia were recruited from three elderly community care centers in Hong Kong. The FAS-C was administered with the Chinese versions of the 5-item Mental Health Inventory (MHI-5), the Zarit Burden Interview (ZBI) and the Revised Memory and Behavioral Problem Checklist (RMBPC).The FAS-C had excellent semantic equivalence with the original version and a content validity index of 0.92. Exploratory factor analysis identified a three-factor structure for the FAS-C (hostile acts, criticism and distancing). Cronbach's alpha of the FAS-C was 0.92. Pearson's correlation indicated that there were significant associations between a higher score on the FAS-C and greater caregiver burden (r=0.66, p0.001), poorer mental health of the caregivers (r=-0.65, p0.001) and a higher level of dementia-related symptoms (frequency of symptoms: r=0.45, p0.001; symptom disturbance: r=0.51, p0.001), which serves to suggest its construct validity. For detecting severe depressive symptoms of the family caregivers, the receiving operating characteristics (ROC) curve had an area under curve of 0.78 (95% confidence interval (CI)=0.69-0.87, p0.0001). The optimal cut-off score was47 with a sensitivity of 0.720 (95% CI=0.506-0.879) and specificity of 0.742 (95% CI=0.643-0.826).The FAS-C is a reliable and valid measure to assess the affective quality of the relationship between Chinese caregivers and their relatives with dementia. It also has acceptable predictability in identifying family caregivers with severe depressive symptoms.

Purpose Rare genetic variants in complement factor I (CFI) that cause low systemic levels of the protein (FI) have been reported as a strong risk factor for advanced age-related macular degeneration (AMD). This study set out to replicate these findings. Methods FI levels were measured by sandwich ELISA in an independent cohort of 276 patients with AMD and 205 elderly controls. Single-nucleotide polymorphism genotyping and Sanger sequencing were used to assess genetic variability. Results The median FI level was significantly lower in those individuals with AMD and a rare CFI variant (28.3 µg/mL) compared to those with AMD without a rare CFI variant (38.8 µg/mL, P = 0.004) or the control population with (41.7 µg/mL, P = 0.0085) or without (41.5 µg/mL, P < 0.0001) a rare CFI variant. Thirty-six percent of patients with AMD with a rare CFI variant had levels below the fifth percentile, compared to 6% in controls with CFI variants. Multiple regression analyses revealed a decreased FI level associated with a rare CFI variant was a risk factor for AMD (early or late AMD: odds ratio [OR] 12.05, P = 0.03; early AMD: OR 30.3, P = 0.02; late AMD: OR 10.64, P < 0.01). Additionally, measurement of FI in aqueous humor revealed a large FI concentration gradient between systemic circulation and the eye (∼286-fold). Conclusions Rare genetic variants in CFI causing low systemic FI levels are strongly associated with AMD. The impermeability of the Bruch's membrane to FI will have implications for therapeutic replacement of FI in individuals with CFI variants and low FI levels at risk of AMD.

In humans, thromboxane (TX) A(2) signals through the TPα and TPβ isoforms of the TXA(2) receptor or TP. Here, the RhoA effector protein kinase C-related kinase (PRK) 1 was identified as an interactant of both TPα and ΤPβ involving common and unique sequences within their respective C-terminal (C)-tail domains and the kinase domain of PRK1 (PRK1(640-942)). Although the interaction with PRK1 is constitutive, agonist activation of TPα/TPβ did not regulate the complex per se but enhanced PRK1 activation leading to phosphorylation of its general substrate histone H1 in vitro. Altered PRK1 and TP expression and signaling are increasingly implicated in certain neoplasms, particularly in androgen-associated prostate carcinomas. Agonist activation of TPα/TPβ led to phosphorylation of histone H3 at Thr(11) (H3 Thr(11)), a previously recognized specific marker of androgen-induced chromatin remodeling, in the prostate LNCaP and PC-3 cell lines but not in primary vascular smooth muscle or endothelial cells. Moreover, this effect was augmented by dihydrotestosterone in androgen-responsive LNCaP but not in nonresponsive PC-3 cells. Furthermore, PRK1 was confirmed to constitutively interact with TPα/TPβ in both LNCaP and PC-3 cells, and targeted disruption of PRK1 impaired TPα/TPβ-mediated H3 Thr(11) phosphorylation in, and cell migration of, both prostate cell types. Collectively, considering the role of TXA(2) as a potent mediator of RhoA signaling, the identification of PRK1 as a bona fide interactant of TPα/TPβ, and leading to H3 Thr(11) phosphorylation to regulate cell migration, has broad functional significance such as within the vasculature and in neoplasms in which both PRK1 and the TPs are increasingly implicated.

BackgroundEmotion dysregulation increases the risk of depression, anxiety, and substance use disorders. Music can help regulate emotions, and mobile phones provide constant access to it. The Music eScape mobile app teaches young people how to identify and manage emotions using music. ObjectiveThis study aimed to examine the effects of using Music eScape on emotion regulation, distress, and well-being at 1, 2, 3, and 6 months. Moderators of outcomes and user ratings of app quality were also examined. MethodsA randomized controlled trial compared immediate versus 1-month delayed access to Music eScape in 169 young people (aged 16 to 25 years) with at least mild levels of mental distress (Kessler 10 score>17). ResultsNo significant differences between immediate and delayed groups on emotion regulation, distress, or well-being were found at 1 month. Both groups achieved significant improvements in 5 of the 6 emotion regulation skills, mental distress, and well-being at 2, 3, and 6 months. Unhealthy music use moderated improvements on 3 emotion regulation skills. Users gave the app a high mean quality rating (mean 3.8 [SD 0.6]) out of 5. ConclusionsMusic eScape has the potential to provide a highly accessible way of improving young people’s emotion regulation skills, but further testing is required to determine its efficacy. Targeting unhealthy music use in distressed young people may improve their emotion regulation skills. Trial RegistrationAustralian New Zealand Clinical Trials Registry ACTRN12615000051549; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=365974

Introduction Elaborated Intrusion (EI) Theory holds that both functional and dysfunctional motivational cognitions are characterized by their intensity, cognitive availability and involvement of imagery, and can be assessed in terms of their frequency and cross-sectional nature. Recently published data on the Motivational Thought Frequency (MTF-A) and State Motivation (SM-A) scales for alcohol control, which were based on EI theory, have shown acceptable fit for a three-subscale structure (Intensity, Imagery, Availability). However, subsequent analyses on the MTF's adaptation to diabetic regimen adherence suggested superior fit from a four-factor model, splitting Imagery into Incentives and Self-Efficacy Imagery. The current paper reanalyzed data on the MTF-A and SM-A, including an additional item on each and using a more robust statistical approach. Methods Participants (n = 504) reporting recent high-risk drinking or were currently trying to control alcohol consumption volunteered to complete an online survey that included the MTF-A, SM-A, Alcohol Use Disorders Identification Test and Readiness to Change Questionnaire. Confirmatory factor analyses employed robust maximum likelihood (MLR) with Yuan-Bentler χ2 adjustment, and presented internal consistencies using omega. Results After omission of multivariate outliers, SM-A data were available from 399 participants, and MTF-A data from 351. Better fit was found for the four-factor model on both measures, and high internal consistencies were obtained for all subscales. Incentives Imagery and Self-Efficacy Imagery were both associated with greater alcohol problems and readiness to change. Conclusions The four-factor structures are statistically superior and more theoretically coherent, and allow a focused assessment of key targets of motivational interventions.

Atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy (C3G) are associated with dysregulation and overactivation of the complement alternative pathway. Typically, gene analysis for aHUS and C3G is undertaken in small patient numbers, yet it is unclear which genes most frequently predispose to aHUS or C3G. Accordingly, we performed a six-center analysis of 610 rare genetic variants in 13 mostly complement genes (CFH, CFI, CD46, C3, CFB, CFHR1, CFHR3, CFHR4, CFHR5, CFP, PLG, DGKE, and THBD) from >3500 patients with aHUS and C3G. We report 371 novel rare variants (RVs) for aHUS and 82 for C3G. Our new interactive Database of Complement Gene Variants was used to extract allele frequency data for these 13 genes using the Exome Aggregation Consortium server as the reference genome. For aHUS, significantly more protein-altering rare variation was found in five genes CFH, CFI, CD46, C3, and DGKE than in the Exome Aggregation Consortium (allele frequency < 0.01%), thus correlating these with aHUS. For C3G, an association was only found for RVs in C3 and the N-terminal C3b-binding or C-terminal nonsurface-associated regions of CFH. In conclusion, the RV analyses showed nonrandom distributions over the affected proteins, and different distributions were observed between aHUS and C3G that clarify their phenotypes.

Psychotic-like experiences (PLEs) have been associated with increased risk of suicidality, but it is unclear whether the level of risk varies with different types of PLE. A cross-sectional online survey was completed by 1610 university students. Respondents completed the Community Assessment of Psychic Experiences-15 (CAPE-P15) assessing PLEs on three subscales: Perceptual Abnormalities (PA), Persecutory Ideation (PI) and Bizarre Experiences (BE). Lifetime suicidal ideation, plans and attempts, cannabis, ecstasy and methamphetamine use and family history of mental disorder were also assessed. Multinomal logistic regression was used to examine unique determinants of lifetime suicidality, defined as any history of (i) suicidal ideation or plans and (ii) any attempt, relative to no lifetime history of suicidality. A lifetime history of PA and PI provided significant unique contributions to the prediction of suicide risk, after control for other significant predictors. BE were not associated with any suicide variable demonstrating the variation in risk of suicidality with different types of PLEs. Perceptual abnormalities and persecutory ideation as measured by the CAPE-P15 are the PLEs associated with a higher risk of lifetime suicidality.

Substance misuse in people with psychosis presents significant problems, but trials of treatments to address it show little sustained advantage over control conditions. An examination of mechanisms underpinning unassisted improvements may assist in the refinement of comorbidity treatments. This study reviewed existing research on natural recovery from substance misuse in people with psychosis. To address this issue, a systematic search identified only 7 articles that fulfilled the criteria. Their results suggest that people with psychosis report similar reasons to change as do non-psychotic groups, although they did not clarify whether the relative frequencies or priority orders were the same. Differences involved issues relating to the disorder and the functional problems faced by this group: receipt of treatment for mental health difficulties, worsening of mental health difficulties, and homelessness. The current research on reasons for change in people with psychosis is sparse and has significant limitations, and as yet it offers little inspiration for new treatments. A more fertile source may prove to be a detailed investigation of successful substance control strategies that are used in self-management by this group.

OBJECTIVE: To explore the effect of education and training on the delivery of alcohol screening and brief intervention and referral to high-risk patients in a hospital setting. Main outcome measures included; delivery of training; practice change in relation to staff performing alcohol screening, brief intervention and referrals. METHODS: Observational study design using mixed methods set in a tertiary referral hospital. Pre-post assessment of medical records and semi-structured interviews with key informants. RESULTS: Routine screening for substance misuse (9% pre / 71.4% post) and wellbeing concerns (6.6% pre / 15 % post) was more frequent following the introduction of resources and staff participation in educational workshops. There was no evidence of a concomitant increase in delivery of brief intervention or referrals to services. Implementation challenges, including time constraints and staff attitudes, and enablers such as collaboration and visible pathways, were identified. CONCLUSION: Rates of patient screening increased, however barriers to delivery of brief intervention and referrals remained. Implementation strategies targeting specific barriers and enablers to introducing interventions are both required to improve the application of secondary prevention for patients in acute settings. IMPLICATIONS: Educational training, formalised liaison between services, systematised early intervention protocols, and continuous quality improvement processes will progress service delivery in this area. Language: en

This study investigates the rates of primary psychotic disorders (PPD) and substance-induced psychotic disorders (SIPDs) in methamphetamine (MA) users accessing needle and syringe programs (NSPs). The aim was to determine if there are systematic differences in the characteristics of MA users with PPDs and SIPDs compared to those with no psychotic disorder. Participants were 198 MA users reporting use in the previous month. Diagnosis was determined using the Psychiatric Research Interview for DSM-IV Substance and Mental Disorders (PRISM-IV). Current psychiatric symptoms and substance use were also measured. Just over half (n=101) of participants met DSM-IV criteria for a lifetime psychotic disorder, including 81 (80%) with a SIPD and 20 (20%) with a PPD. Those with a younger age of onset of weekly MA use were at increased risk of a lifetime SIPD. A current psychotic disorder was found in 62 (39%), comprising 49 SIPDs (79%) and 13 PPDs (21%). MA users with a current PPD were more likely to have received psychiatric treatment in the past month than those with a current SIPD, despite a similar level of psychotic symptom severity. A high proportion of MA users accessing NSPs have psychotic disorders, the majority of which are substance-induced.

Autoantibody formation against Factor H (FH) is found in 7–10% of patients who are diagnosed with atypical haemolytic uraemic syndrome (aHUS). These autoantibodies predominately target the C-terminal cell binding recognition domain of FH and are associated with absence of FHR1. Additional autoantibodies have also been identified in association with aHUS, for example autoantibodies to Factor I. Based on this, and that there are genetic mutations in other complement regulators and activators associated with aHUS, we hypothesised that other complement regulator proteins, particularly surface bound regulators in the kidney, might be the target for autoantibody formation in aHUS. Therefore, we assayed serum derived from 89 patients in the Newcastle aHUS cohort for the presence of autoantibodies to CD46 (membrane cofactor protein, MCP), CD55 (decay accelerating factor, DAF), CD35 (complement receptor type 1, CR1; TP10) and CD59. We also assayed 100 healthy blood donors to establish the normal levels of reactivity towards these proteins in the general population. Recombinant proteins CD46 and CD55 (purified from Escherichia coli) as well as soluble CR1 (CD35) and oligomeric C4BP-CD59 (purified from eukaryotic cell media) were used in ELISA to detect high responders. False positive results were established though Western blot and flow cytometric analysis. After excluding false positive responders to bacterial proteins in the CD46 and CD55 preparations, and responses to blood group antigens in CD35, we found no significant level of patient serum IgG reactivity with CD46, CD55, CD35 or CD59 above that detected in the normal population. These results suggest that membrane anchored complement regulators are not a target for autoantibody generation in aHUS.

The complement inhibitor eculizumab is a humanized monoclonal antibody against C5. It was developed to specifically target cleavage of C5 thus preventing release of C5a and activation of the terminal pathway. Paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS) are 2 diseases with distinctly different underlying molecular mechanisms. In PNH, progeny of hematopoietic stem cells that harbor somatic mutations lead to a population of peripheral blood cells that are deficient in complement regulators resulting in hemolysis and thrombosis. In aHUS, germline mutations in complement proteins or their regulators fail to protect the glomerular endothelium from complement activation resulting in thrombotic microangiopathy and renal failure. Critical to the development of either disease is activation of the terminal complement pathway. Understanding this step has led to the study of eculizumab as a treatment for these diseases. In clinical trials, eculizumab is proven to be effective and safe in PNH and aHUS.

Introduction Research shows disproportionate levels of substance use among sexual minority young people. A range of reasons for these disparities have been suggested, including connectedness to and participation in the LGBT community. Little is known about how these constructs are related to substance use involvement in sexual minority (sub)groups or how these relationships are affected by other factors. Methods 1266 young sexual minority Australians completed a cross-sectional online survey. Multiple regressions were conducted to assess associations between connectedness to and participation in the LGBT community on substance use involvement, before and after controlling for other factors such as substance use motives, psychological distress, wellbeing, resilience, minority stress, and age. Results/conclusion Most participants identified as homosexual (57%, n = 726) and male (54%, n = 683). In the overall sample, participation in and connectedness the LGBT community were significantly associated with increased substance use involvement before (F(2,1263) = 35.930, p ≤ 0.001, R2 = 0.052) and after controlling for other variables (F(8,1095) = 33.538, p ≤ 0.001, R2 = 0.191), with meaningfully higher effect sizes for participation than for connectedness. After controlling for other variables, connectedness only remained significant for homosexuals. Effect sizes for participation were higher for females than males, and bisexuals than homosexuals. However, participation in the LGBT Community was not associated with substance use in participants identifying with a non-binary gender identity. In conclusion, substance use involvement was associated with participation in the LGBT community, but connectedness to the LGBT community only had a weak association with substance use involvement in the homosexual subgroup.

Effective motivational support is needed in chronic disease management. This study was undertaken to improve a novel type 2 diabetes motivational intervention, (functional imagery training, FIT) based on participant feedback and results from a self-management randomised controlled trial.Qualitative inductive thematic analysis of semi-structured interviews.Open-ended questions on participant experiences of the FIT intervention content, process, most/least helpful features, suggestions for improvement and general feedback.Eight themes emerged. Participants thought FIT promoted autonomy and self-awareness. They found the intervention interesting and helpful in keeping their health on track through accountability provided by regular phone calls. However, boredom with repetitive use of imagery, feeling inadequately equipped to manage unhealthy cravings, and difficulty with the time commitment was reported by some. Supplementary written material was recommended.Several well-received features of FIT overlapped with those from traditional motivational interviewing. FIT sessions should ensure content is regularly adapted to new health-enhancing goals. After self-management behaviour becomes habitual, imagery practice could be restricted to challenging contexts. Provision of a written rationale and use of mindfulness for cravings is recommended. With these improvements, the impact of FIT on diabetic control may be substantially enhanced.

The Family Attitude Scale (FAS) is a self-report measure of critical or hostile attitudes and behaviors towards another family member, and demonstrates an ability to predict relapse in psychoses. Data are not currently available on a French version of the scale. The present study developed a French version of the FAS, using a large general population sample to test its internal structure, criterion validity and relationships with the respondents' symptoms and psychiatric diagnoses, and examined the reciprocity of FAS ratings by respondents and their partners. A total of 2072 adults from an urban population undertook a diagnostic interview and completed self-report measures, including an FAS about their partner. A subset of participants had partners who also completed the FAS. Confirmatory factor analyses revealed an excellent fit by a single-factor model, and the FAS demonstrated a strong association with dyadic adjustment. FAS scores of respondents were affected by their anxiety levels and mood, alcohol and anxiety diagnoses, and moderate reciprocity of attitudes and behaviors between the partners was seen. The French version of the FAS has similarly strong psychometric properties to the original English version. Future research should assess the ability of the French FAS to predict relapse of psychiatric disorders.

Background Depression and alcohol misuse are among the most prevalent diagnoses in suicide fatalities. The risk posed by these disorders is exacerbated when they co-occur. Limited research has evaluated the effectiveness of common depression and alcohol treatments for the reduction of suicide vulnerability in individuals experiencing comorbidity. Methods Participants with depressive symptoms and hazardous alcohol use were selected from two randomised controlled trials. They had received either a brief (1 session) intervention, or depression-focused cognitive behaviour therapy (CBT), alcohol-focused CBT, therapist-delivered integrated CBT, computer-delivered integrated CBT or person-centred therapy (PCT) over a 10-week period. Suicidal ideation, hopelessness, depression severity and alcohol consumption were assessed at baseline and 12-month follow-up. Results Three hundred three participants were assessed at baseline and 12 months. Both suicidal ideation and hopelessness were associated with higher severity of depressive symptoms, but not with alcohol consumption. Suicidal ideation did not improve significantly at follow-up, with no differences between treatment conditions. Improvements in hopelessness differed between treatment conditions; hopelessness improved more in the CBT conditions compared to PCT and in single-focused CBT compared to integrated CBT. Limitations Low retention rates may have impacted on the reliability of our findings. Combining data from two studies may have resulted in heterogeneity of samples between conditions. Conclusions CBT appears to be associated with reductions in hopelessness in people with co-occurring depression and alcohol misuse, even when it is not the focus of treatment. Less consistent results were observed for suicidal ideation. Establishing specific procedures or therapeutic content for clinicians to monitor these outcomes may result in better management of individuals with higher vulnerability for suicide.

article i nfo Objective: Psychotic-like experiences (PLEs) are common, and are markers of poor mental health. This study examined the internal structure of a screening test, the Community Assessment of Psychic Experiences- Positive scale (CAPE-P) in a young Australian sample. Method: A cross-sectional online survey, which included the CAPE-P, was completed by 1610 university students aged between 18 and 25 years. Confirmatory factor analyses compared 1-, 4-, and 5-factor models, and examined effects of omitting selected items. Results: A 3-factor model, omitting items on magical thinking, grandiosity, paranormal beliefs and a cross-loading item produced the best fit. The resultant 15-item CAPE (CAPE-P15) had three subscales - Persecutory Ideation, Perceptual Abnormalities and Bizarre Experiences, all with high levels of internal consistency. Conclusion: The CAPE-P15 shows promise as a measure of positive, psychosis-like experiences, but further validation of this measure is required in community samples. © 2013 Published by Elsevier B.V.

Brief interventions are effective for problem drinking and reductions are known to occur in association with screening and assessment. The present study sought to assess, among participants (N=202) in a clinical trial, how much change occurred between baseline assessment and a one-session brief intervention (S1), and the predictors of early change. The primary focus was on changes in the Beck Depression Inventory Fast Screen scores and alcohol consumption (standard drinks per week) prior to random allocation to nine further sessions addressing either depression, alcohol, or both problems. There were large and clinically significant reductions between baseline and S1, with the strongest predictors being baseline scores in the relevant domain and change in the other domain. Client engagement was also predictive of early depression changes. Monitoring progress in both domains from first contact, and provision of empathic care, followed by brief intervention appear to be useful for this high prevalence comorbidity.

© The Author 2016. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. Background This study examines substance use disparities among homosexual, bisexual and heterosexual adolescents and young adults from nine countries. Methods Data from 58 963 respondents (aged 16 and 35 years) to the 2015 'Global Drug Survey' were utilized. Rates of lifetime, last-year, last-month use and age of onset of 13 different substances were compared across sexual identity subgroups. Results Adolescents and young adults with a sexual minority identity generally reported higher rates of substance use and an earlier age of onset compared to their heterosexual counterparts. Differences in substance use were larger among female groups than male groups, and rates of substance use were generally higher among bisexuals than homosexuals of both genders. Conclusion Higher rates of substance use in bisexuals compared with homosexuals among both genders and larger differences between female groups highlight the importance of differentiating between sexual minority identities in substance use research, and in designing substance misuse interventions for people with a sexual minority identity.

Background Personality disorders are highly comorbid with alcohol misuse and depressive symptomatology; however, few studies have investigated treatment outcomes in this population. The aim of this study was to examine relationships between baseline personality disorder cluster profiles and overall and treatment-related changes for those with co-occurring alcohol misuse and depression. Methods Secondary analysis was conducted using a subset of data (N = 290) from two randomised controlled trials of psychological interventions for co-occurring alcohol misuse and depression, which did not specifically target personality disorders. Baseline dimensional personality disorder cluster scores were derived from the International Personality Disorder Examination Questionnaire (IPDEQ). Four treatment conditions were compared: a brief integrated intervention, followed by no further treatment, or nine further sessions of integrated-, alcohol-, or depression-focused treatment. Associations between IPDEQ scores and changes in alcohol use, depressive symptoms and functioning from baseline to the 6- and the 12-month follow-ups were of primary interest. Results Personality disorder cluster scores moderately negatively impacted on overall change (primarily Cluster C), as well as treatment-related outcomes (primarily Cluster A), particularly changes in depressive symptoms and psychosocial functioning. Longer interventions appeared to be more effective in the longer-term (e.g., at 12-month follow-up), with integrated interventions relatively more effective than single-focused ones for individuals with higher personality disorder cluster scores. Conclusions Greater attention needs to be paid to particular personality disorder clusters during the assessment and treatment of individuals with co-occurring alcohol misuse and depression. Integrated interventions, incorporating motivational interviewing and cognitive behaviour therapy, may provide a useful therapeutic framework. Integrated interventions also provide opportunities for adjunctive components focussing on other issues and coping strategies (e.g., to offset negative affective states), potentially tailored to the characteristics and needs of individual participants.

Background: There is some evidence that, in contrast to depressed women, depressed men tend to report alternative symptoms that are not listed as standard diagnostic criteria. This may possibly lead to an under- or misdiagnosis of depression in men. Aims: This study aims to clarify whether depressed men and women report different symptoms. Methods: This study used data from the 2007 Australian National Survey of Mental Health and Wellbeing that was collected using the World Health Organization’s Composite International Diagnostic Interview. Participants with a diagnosis of a depressive disorder with 12-month symptoms ( n = 663) were identified and included in this study. Differential item functioning (DIF) was used to test whether depressed men and women endorse different features associated with their condition. Results: Gender-related DIF was present for three symptoms associated with depression. Depressed women were more likely to report ‘appetite/weight disturbance’, whereas depressed men were more likely to report ‘alcohol misuse’ and ‘substance misuse’. Conclusion: While the results may reflect a greater risk of co-occurring alcohol and substance misuse in men, inclusion of these features in assessments may improve the detection of depression in men, especially if standard depressive symptoms are under-reported.

Background: Standardized alcohol craving scales are rarely used outside of research environments despite recognized clinical utility. Scale length is a key barrier to more widespread application. A brief measure of alcohol craving is needed to improve research and treatment of alcohol use disorders (AUDs). Grounded in the Elaborated Intrusion Theory of Desire, the Alcohol Craving Experience (ACE) Questionnaire comprises two 11-item self-report scales that assess past-week frequency and maximum strength of alcohol craving. This study aimed to create a brief version of the ACE while maintaining psychometric integrity and clinical utility. Methods: Patients attending a university hospital alcohol and drug outpatient service for the treatment of AUD completed the ACE as part of a questionnaire battery. Three patient samples were utilized: 519 patients with pretreatment and outcome data, 228 patients with pretreatment data, and 66 patients who completed the ACE at treatment sessions 1 and 2. Results: The Frequency scale of the ACE possessed greater clinical utility and predictive validity than the Strength scale. Revision of the Frequency measure produced a 5-item “Mini Alcohol Craving Experience” (MACE) Questionnaire. Satisfactory validity (construct, predictive, concurrent, convergent, and incremental) and reliability (internal and test–retest) were maintained. A 1 standard deviation increase in pretreatment MACE score was associated with a 54 percentage increase in the odds of patient lapse or dropout. Conclusions: The MACE provides a brief, theoretically, and psychometrically robust measure of alcohol craving suitable for use with AUD populations in time-limited clinical and research settings.