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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.

Background Internet-based parental programmes may improve parental wellbeing and mitigate the burden of mental health issues during the perinatal period. However, few studies have explored the cost and clinical impacts of such interventions. In the present study, we sought to evaluate the cost-effectiveness associated with an online cognitive behaviour therapy intervention ( Baby Steps Wellbeing) to an information-only programme (Baby Care). Methods An alongside-trial cost-effectiveness analysis was undertaken using data from a randomised clinical trial comparing the Baby Steps Wellbeing intervention to Baby Care. Direct healthcare costs, as well as indirect costs attributed to income loss, were considered. The Assessment of Quality of Life-8 Dimensions multi-attribute utility instrument was used to estimate participant utilities, and subsequently calculate quality-adjusted life years (QALYs). Incremental cost-effectiveness ratios were calculated to assess the cost-effectiveness of the intervention. The economic evaluation adopted a societal perspective. Results In total, 496 parents were randomised to either the Baby Steps Wellbeing intervention or the Baby Care control arm. No significant differences in costs (−$27, 95% confidence interval (CI): −$1189–$1134) or QALYs (0.051, 95% CI: −0.097–0.200) were identified. Bootstrapped results showed that the Baby Steps Wellbeing programme was cost-saving and health improving in 38% of simulations and cost-effective in another 37% of simulations. Conclusions The Baby Steps Wellbeing programme was slightly cost-saving with slightly improved health outcomes compared with Baby Care. Bootstrapped results indicate the Baby Steps Wellbeing was cost-effective in 75% of simulations. Overall, the Baby Steps Wellbeing programme is an online programme that is cost-effective. Trial registration Australian & New Zealand Clinical Trials Registry: ANZCTR12614001256662.

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.

The final year of high school is a challenging phase of adolescents’ lives and substance use can play an important role. We examined changes in the frequency and quantity of alcohol and cannabis use, and demographic correlates among Grade 12 students of 2020. Students (N = 844) from nine schools retrospectively self-reported changes in substance use after the easing of COVID-19 lockdowns (back to school), compared to before the pandemic. Changes in use were examined with age, gender, Aboriginal or Torres Islander, parental and family characteristics, and truancy. Thirty-one percent of students reported that they used alcohol less frequently, and 24% reported that they used it more frequently compared to pre-COVID-19. Most students (46%) reported that they used cannabis less, while a subset reported using more frequently (22%). A history of truancy was associated with an increased frequency (OR = 2.13 [1.18–3.83]) of cannabis use. A substantial minority of adolescents used more alcohol and cannabis after the initial COVID-19 lockdown period. Students in their final year who reported increased use may benefit from increased support to manage their substance use.

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.

Young people with cystic fibrosis face significant physical discomfort and an extensive treatment burden that often includes lengthy hospital stays and increased risk for psychological distress. With many treatments being critically important, parents are often compelled to act as translators between the child patient and medical staff. An inadvertent consequence of this dynamic is that young patients can be hindered from freely discussing their personal experiences of cystic fibrosis (CF) and finding ways to ameliorate their distress. In similar situations, social robots (SR) have been shown to help overcome such hindrances. Two studies were conducted. An online study (N = 132) assessed young people’s views of potentially creating a storybook of their experiences with CF and interacting with a SR. Secondly, a feasibility study tested the use of an SR delivering an intervention for CF that has given significant reductions in anxiety—the Metacognitive Intervention of Narrative Imagery (MINI). Eight patients, aged 10–14 years, received three 1-h sessions and were assessed on anxiety, depression, and metacognitive beliefs. Participants showed improvements in anxiety and the metacognitive beliefs of negative meta-worry and superstition, punishment and responsibility, all with large effect sizes. Participants and parents rated the intervention and robot highly on favourability and usability. Participant ratings after interacting with the social robot were considerably higher than other young patients who only viewed a brief video of the robot, indicating conversing with the robot may improve their perception of it. These findings provide additional evidence of the MINI’s effectiveness in reducing anxiety and certain negative metacognitive beliefs. This study also provides preliminary evidence that there may be added benefits from using a social robot to implement the MINI.

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.

Recessive mutations in diacylglycerol kinase epsilon (DGKE) display genetic pleiotropy, with pathological features reported as either thrombotic microangiopathy or membranoproliferative glomerulonephritis (MPGN), and clinical features of atypical hemolytic uremic syndrome (aHUS), nephrotic syndrome or both. Pathophysiological mechanisms and optimal management strategies have not yet been defined. In prospective and retrospective studies of aHUS referred to the United Kingdom National aHUS service and prospective studies of MPGN referred to the National Registry of Rare Kidney Diseases for MPGN we defined the incidence of DGKE aHUS as 0.009/million/year and so-called DGKE MPGN as 0.006/million/year, giving a combined incidence of 0.015/million/year. Here, we describe a cohort of sixteen individuals with DGKE nephropathy. One presented with isolated nephrotic syndrome. Analysis of pathological features reveals that DGKE mutations give an MPGN-like appearance to different extents, with but more often without changes in arterioles or arteries. In 15 patients presenting with aHUS, ten had concurrent substantial proteinuria. Identified triggering events were rare but coexistent developmental disorders were seen in six. Nine with aHUS experienced at least one relapse, although in only one did a relapse of aHUS occur after age five years. Persistent proteinuria was seen in the majority of cases. Only two individuals have reached end stage renal disease, 20 years after the initial presentation, and in one, renal transplantation was successfully undertaken without relapse. Six individuals received eculizumab. Relapses on treatment occurred in one individual. In four individuals eculizumab was withdrawn, with one spontaneously resolving aHUS relapse occurring. Thus we suggest that DGKE-mediated aHUS is eculizumab non-responsive and that in individuals who currently receive eculizumab therapy it can be safely withdrawn. This has important patient safety and economic implications., Graphical abstract

BackgroundMethamphetamine has been consistently associated with positive psychotic symptoms, but little is known about whether the reverse also occurs.AimsThis study determined whether the relationship between methamphetamine use and positive psychotic symptoms is bidirectional over 12 months. The impact of lifetime psychotic disorders and methamphetamine dependence on these relationships was also examined.MethodA total of 201 regular (at least monthly) primary methamphetamine users were recruited from free needle and syringe programmes in three Australian cities. Data on the frequency of methamphetamine and other drug use (from Timeline Followback inteviews) and the severity of positive psychotic symptoms (using the Brief Psychiatric Rating Scale) in the past 2 weeks were collected in 12 contiguous monthly face-to-face interviews (mean of 9.14/11 (s.d. = 3.16) follow-ups completed). Diagnoses were derived using the Psychiatric Research Interview for DSM-IV Substance and Mental Disorders.ResultsThe mean age of participants was 31.71 years (s.d. = 8.19) and 39% (n = 77) were women. At baseline 55% (n = 110) were dependent on methamphetamine and 51% (n = 102) had a lifetime psychotic disorder. Cross-lagged dynamic panel models found a significant bidirectional relationship between psychotic symptoms and methamphetamine use (Comparative Fit Index (CFI) = 0.94, standardised root mean square residual (SRMR) = 0.05, root mean square error of approximation (RMSEA) = 0.05, 95% CI 0.04–0.06). The magnitude of the relationship in each direction was similar, and the presence of methamphetamine dependence or a lifetime psychotic disorder did not have an impact on results.ConclusionsA dynamic, bidirectional relationship between methamphetamine and psychotic symptoms of similar magnitude in each direction was found over 1 year. This suggests integrated treatments that target methamphetamine, psychotic symptoms and their interrelationship may be of most benefit.

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

Background The high burden of chronic kidney disease in First Nations peoples requires urgent attention. Empowering people to self-manage their own condition is key, along with promotion of traditional knowledge and empowerment of First Nations communities. This study explores the potential of a culturally responsive tool, already found to have high acceptability and feasibility among First Nations people, to support self-management for First Nations people with kidney failure. The Stay Strong app is a holistic wellbeing intervention. This study explores the suitability of the Stay Strong app to support self-management as shown by the readiness of participants to engage in goal setting. Data were collected during a clinical trial which followed adaption of research tools and procedures through collaboration between content and language experts, and community members with lived experience of kidney failure. Methods First Nations (i.e., Aboriginal and Torres Strait Islander) participants receiving haemodialysis in the Northern Territory (n = 156) entered a three-arm, waitlist, single-blind randomised controlled trial which provided collaborative goal setting using the Stay Strong app at baseline or at 3 months. Qualitative data gathered during delivery of the intervention were examined using both content and thematic analysis. Results Almost all participants (147, 94%) received a Stay Strong session: of these, 135 (92%) attended at least two sessions, and 83 (56%) set more than one wellbeing goal. Using a deductive approach to manifest content, 13 categories of goals were identified. The three most common were to: ‘connect with family or other people’, ‘go bush/be outdoors’ and ‘go home/be on country’. Analysis of latent content identified three themes throughout the goals: ‘social and emotional wellbeing’, ‘physical health’ and ‘cultural connection’. Conclusion This study provides evidence of the suitability of the Stay Strong app for use as a chronic condition self-management tool. Participants set goals that addressed physical as well as social and emotional wellbeing needs, prioritising family, country, and cultural identity. The intervention aligns directly with self-management approaches that are holistic and prioritise individual empowerment. Implementation of self-management strategies into routine care remains a key challenge and further research is needed to establish drivers of success.

Social robots have been used to promote health education and coaching to provide health information. Important behaviors to address and monitor include actions that can be modified, such as physical activity. These behaviours often require different personalised recommendations. Robots could be an effective way to give personalised health feedback based on scores, including in acute medical settings. This trial involved an automated social robot interaction in a health clinic to collect health data and provide personalized feedback on four key factors: exercise, diet, alcohol and cigarette use. Patients completed an 20-minute health questionnaire with a Pepper Robot in a clinic room during a health visit. The interaction was programmed to run autonomously with automatic scoring and feedback based on health scores. Instructions were delivered using co-verbal speech and detailed text on the tablet. Questions also included ratings on comfort to discuss health topics with a human or robot. Patients could choose to receive an optional follow-up in four weeks’ time. A total of 47 patients completed the session. Patients reported being as comfortable to discuss health-related topics with a robot or human for exercise, diet, alcohol, cigarette use, and mental health. Program evaluation received moderate ratings for the robot on ease of use, usefulness and motivation to change a health behavior. No significant health changes were found 30 days later due to high initial health scores, leaving little room for improvement. This initial proof-of-concept trial found that a robot-delivered service could be deployed in a live health clinic in conjunction with patient visits.

Objective To understand health practitioners' attitudes towards the acceptability and usability of the Head to Health digital gateway. Design Feedback surveys were completed by health care practitioners to identify experiences with and perceptions of the digital mental health gateway Head to Health. Data from the surveys were evaluated via thematic analysis. Settings and participants Health care practitioners working in mental health settings participated in three digital mental health workshops facilitated by Queensland University of Technology in 2018. A total of 43 participants explored key features of the Head to Health site and provided feedback via a post‐workshop survey. Main outcome measures Clinician feedback about usability, utility, barriers to integration and promotion of the Head to Health digital mental health gateway. Results Practitioner feedback highlighted that although many were unaware of the website, overall perceptions were positive with 79% stating they will recommend the site to clients in the future. Thematic analysis revealed four overarching thematic headings; “utility of the Head to Health portal,” “usability,” “clinician recommendations” and “clinician‐led” promotional strategies. Health professionals identified a number of roles they can play in assisting to promote Head to Health more widely. Conclusion Overall Head to Health is perceived to be a quality resource of value to health practitioners. There is a need for ongoing government and clinician‐led promotion of Head to Health both generally and in the rural setting. Guidelines are required on integration of digital mental health resources into clinical practice.

The relationship between mental well-being and distress in young people is unclear but important for both theoretical and practical reasons. This study tests these relationships using both dimensional and categorical measures of mental well-being and distress. Two thousand and eighty-two Australians’ (16–25 years) completed an online survey. A subsample (n = 389) completed diagnostic telephone interviews to identify 12-month DSM-IV mood, anxiety and substance use disorders. Five competing models of the relationship between mental well-being and distress were compared. Only the bifactor model fit the data, indicating both mental well-being and distress are important subcomponents of a young person’s overall level of mental health. Over 90% of young people had flourishing or moderate well-being and only 6% were languishing. Those with past year mental disorders were only 15% less likely to be flourishing and 4% more likely to be languishing. These findings highlight the well-being potential of young people living with and without mental disorders.

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.

Violent threats are common and, in the majority of cases, innocuous expressions of emotion. However, some threats result in violence and mental illness is a predictor for threat-related violence (T...

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.

Item does not contain fulltext The C3 glomerulopathies are a group of rare kidney diseases characterized by complement dysregulation occurring in the fluid phase and in the glomerular microenvironment, which results in prominent complement C3 deposition in kidney biopsy samples. The two major subgroups of C3 glomerulopathy - dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) - have overlapping clinical and pathological features suggestive of a disease continuum. Dysregulation of the complement alternative pathway is fundamental to the manifestations of C3 glomerulopathy, although terminal pathway dysregulation is also common. Disease is driven by acquired factors in most patients - namely, autoantibodies that target the C3 or C5 convertases. These autoantibodies drive complement dysregulation by increasing the half-life of these vital but normally short-lived enzymes. Genetic variation in complement-related genes is a less frequent cause. No disease-specific treatments are available, although immunosuppressive agents and terminal complement pathway blockers are helpful in some patients. Unfortunately, no treatment is universally effective or curative. In aggregate, the limited data on renal transplantation point to a high risk of disease recurrence (both DDD and C3GN) in allograft recipients. Clinical trials are underway to test the efficacy of several first-generation drugs that target the alternative complement pathway.

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.

Rare variants in the complement factor I (CFI) gene, associated with low serum factor I (FI) levels, are strong risk factors for developing the advanced stages of age-related macular degeneration (AMD). No studies have been undertaken on the prevalence of disease-causing CFI mutations in patients with geographic atrophy (GA) secondary to AMD. A multicenter, cross-sectional, noninterventional study was undertaken to identify the prevalence of pathogenic rare CFI gene variants in an unselected cohort of patients with GA and low FI levels. A genotype-phenotype study was performed. Four hundred and sixty-eight patients with GA secondary to AMD were recruited to the study, and 19.4% (n = 91) demonstrated a low serum FI concentration (below 15.6 μg/ml). CFI gene sequencing on these patients resulted in the detection of rare CFI variants in 4.7% (n = 22) of recruited patients. The prevalence of CFI variants in patients with low serum FI levels and GA was 25%. Of the total patients recruited, 3.2% (n = 15) expressed a CFI variant classified as pathogenic or likely pathogenic. The presence of reticular pseudodrusen was detected in all patients with pathogenic CFI gene variants. Patients with pathogenic CFI gene variants and low serum FI levels might be suitable for FI supplementation in therapeutic trials.

BackgroundAdolescence is a life stage characterized by intense development and increased vulnerability. Yet, young people rarely seek help for mental health, often due to stigma and embarrassment. Alarmingly, even those who do seek help may not be able to receive it. Interventions focused on well-being offer a protective factor against adversity. Highly effective, innovative, theoretically sound, accessible, and engaging mobile health (mHealth) interventions that can be used to look beyond mental ill-health and toward mental well-being are urgently needed.ObjectiveWe aimed to explore how young Australians conceptualize and construct recovery journeys from feeling unwell to being well in order to inform the conceptual design of a youth-led information-, resource-, and support-focused mHealth intervention.MethodsA sample of young people, grouped by age (12-15 years, 16-19 years, and 20-25 years), took part in 3 in-person participatory design workshops (per group). Young people’s understanding and representation of well-being, feeling unwell, and the recovery journey were investigated using visual and linguistic data collection methods: photo elicitation and journey mapping. A social constructionist perspective was used for thematic analysis to produce a conceptual model of the recovery journey. A mobile app was co-designed and all app functions were mapped through iterative development and testing by young people and a team of psychology, research, design and information technology experts.ResultsYoung people (n=25) described a 6-stage journey with specific barriers and coping strategies. The findings, when situated within the personal recovery framework in mental health, emphasize the cyclic and iterative model of change. Through co-design, the new app—Niggle—was conceptualized as a visual representation of an amorphous problem, which can be addressed through app functions corresponding to the most helpful strategies that young people used to progress through the stages of their recovery journey.ConclusionsNiggle is available to offer support to young people for a range of problems and provides a hot link to counseling services in Australia. This paper elaborates on the process of in-depth qualitative data collection through visual, linguistic, and co-design methods. The findings of this study give insight into young people’s understanding of well-being and recovery. This paper could aid the development of high-quality personalized mHealth interventions and support resources.

BACKGROUND: Atypical haemolytic uraemic syndrome (aHUS) is a rare disorder characterised by thrombocytopenia, microangiopathic haemolytic anaemia, and acute kidney injury. The condition is primarily caused by inherited or acquired dysregulation of complement regulatory proteins with ~40% of those affected aged < 18 years. Historically, kidney failure and death were common outcomes, however, improved understanding of the condition has led to discovery of novel therapies. OBJECTIVES: To evaluate the benefits and harms of interventions for aHUS. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies for randomised controlled studies (RCTs) up to 3 September 2020 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. MEDLINE(OVID) 1946 to 27 July 2020 and EMBASE (OVID) 1974 to 27 July 2020 were searched for non‐RCTs. SELECTION CRITERIA: All randomised and non‐randomised clinical trials comparing an intervention with placebo, an intervention with supportive therapy, or two or more interventions for aHUS were included. Given the rare nature of the condition in question, prospective single‐arm studies of any intervention for aHUS were also included. DATA COLLECTION AND ANALYSIS: Two authors independently extracted pre‐specified data from eligible studies and evaluated risk of bias using a newly developed tool based on existing Cochrane criteria. As statistical meta‐analysis was not appropriate, qualitative analysis of data was then performed. MAIN RESULTS: We included five single‐arm studies, all of which evaluated terminal complement inhibition for the treatment of aHUS. Four studies evaluated the short‐acting C5 inhibitor eculizumab and one study evaluated the longer‐acting C5 inhibitor ravulizumab. All included studies within the review were of non‐randomised, single‐arm design. Thus, risk of bias is high, and it is challenging to draw firm conclusions from this low‐quality evidence. One hundred patients were included within three primary studies evaluating eculizumab, with further data reported from 37 patients in a secondary study. Fifty‐eight patients were included in the ravulizumab study. After 26 weeks of eculizumab therapy there were no deaths and a 70% reduction in the number of patients requiring dialysis. Complete thrombotic microangiopathic (TMA) response was observed in 60% of patients at 26 weeks and 65% at two years. After 26 weeks of ravulizumab therapy four patients had died (7%) and complete TMA response was observed in 54% of patients. Substantial improvements were seen in estimated glomerular filtration rate and health‐related quality of life in both eculizumab and ravulizumab studies. Serious adverse events occurred in 42% of patients, and meningococcal infection occurred in two patients, both treated with eculizumab. AUTHORS' CONCLUSIONS: When compared with historical data, terminal complement inhibition appears to offer favourable outcomes in patients with aHUS, based upon very low‐quality evidence drawn from five single‐arm studies. It is unlikely that an RCT will be conducted in aHUS and therefore careful consideration of future single‐arm data as well as longer term follow‐up data will be required to better understand treatment duration, adverse outcomes and risk of disease recurrence associated with terminal complement inhibition.