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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.

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.

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.

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.

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.

In 2007 and 2009, the regulatory approval of the first-in-class complement inhibitor eculizumab revolutionized the clinical management of 2 rare, life-threatening clinical conditions: paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). Although being completely distinct diseases affecting blood cells and the glomerulus, PNH and aHUS remarkably share several features in their etiology and clinical presentation. An imbalance between complement activation and regulation at host surfaces underlies both diseases precipitating in severe thrombotic events that are largely resistant to anticoagulant and/or antiplatelet therapies. Inhibition of the common terminal complement pathway by eculizumab prevents the frequently occurring thrombotic events responsible for the high mortality and morbidity observed in patients not treated with anticomplement therapy. Although many in vitro and ex vivo studies elaborate numerous different molecular interactions between complement activation products and hemostasis, this review focuses on the clinical evidence that links these 2 fields in humans. Several noninfectious conditions with known complement involvement are scrutinized for common patterns concerning a prothrombotic statues and the occurrence of certain complement activation levels. Next to PNH and aHUS, germline-encoded CD59 or CD55 deficiency (the latter causing the disease complement hyperactivation, angiopathic thrombosis, and protein-losing enteropathy), autoimmune hemolytic anemia, (catastrophic) antiphospholipid syndrome, and C3 glomerulopathy are considered. Parallels and distinct features among these conditions are discussed against the background of thrombosis, complement activation, and potential complement diagnostic and therapeutic avenues.

While periodontal disease is associated with many risk factors, socioeconomically disadvantaged communities experience the highest disease burden. The aim of this study was to evaluate the effectiveness of a personalized oral health education program, in combination with routine dental treatment, in participants from a low socioeconomic community. We used a randomized, controlled, examiner-blinded clinical trial. A total of 579 participants (aged 18&ndash, 60 years) were randomly grouped: the intervention group (n = 292) received a personalized oral health education program in combination with routine dental care and the control group (n = 287) received routine dental care. All participants were assessed for improvement in oral health care behaviors, dental plaque, and periodontal status at baseline, 12 months, and 24 months. We found a significant drop (p &lt, 0.001) in the plaque indices, Periodontal Probing Depths (PPD) and Bleeding on Probing (BOP) between baseline and the 12-month follow-up for both groups. For BOP, the number of sites positive was significantly different between baseline and the 24-month follow-up (p = 0.037). No differences were found between the two groups for any evaluated clinical outcome. The personalized oral health education program used in the current study did not appear to add significant improvement to clinical outcomes of periodontal health compared with routine restorative dental care per se.

While significantly elevated distress is repeatedly found amongst young people with cystic fibrosis, their determinants remain largely unknown. This study explored whether metacognitive beliefs and self-efficacy for emotion regulation were associated with anxiety and depression after control for physical functioning, age and gender.Cross-sectional study using a 110-item online questionnaire.An online survey was undertaken by 147 young people with CF aged 10-18 from five countries. Associations of Hospital Anxiety and Depression Scale scores with gender, age, physical functioning, Metacognitive Beliefs Questionnaire for Children (MCQ-C) subscales and Self-Efficacy for Emotion Regulation (SE-ER) were examined using hierarchical multiple linear regressions.Physical functioning, gender and age accounted for 31% of the variance in anxiety and 39% in depression. The MCQ-C and SE-ER added another 45% to the variance of anxiety and 32% to depression. At the final step of both analyses, physical functioning, SE-ER, MCQ-C Negative Meta-Worry and Superstition, PunishmentResponsibility contributed significantly. Older age was also significantly associated with depression.Self-efficacy for emotion regulation, concern about worrying and shame may be particularly important foci for interventions aimed at ameliorating anxiety and depression in young people with CF.

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.

Genomics is revolutionizing biomedical research, medicine and healthcare globally in academic, public and industry sectors alike. Concrete examples around the world show that huge benefits for patients, society and economy can be accrued through effective and responsible genomic research and clinical applications. Unfortunately, Ireland has fallen behind and needs to act now in order to catch up. Here, we identify key issues that have resulted in Ireland lagging behind, describe how genomics can benefit Ireland and its people and outline the measures needed to make genomics work for Ireland and Irish patients. There is now an urgent need for a national genomics strategy that enables an effective, collaborative, responsible, well-regulated, and patient centred environment where genome research and clinical genomics can thrive. We present eight recommendations that could be the pillars of a national genomics health strategy.

Background Self-care in diabetic foot disease (DFD) is challenging and can contribute to poor outcomes. Motivational Interviewing (MI) engages people in self-care and integrating imagery may further improve its outcomes. No previous studies have trained podiatrists in using MI to address DFD self-care. This was the first study on training podiatrists to conduct imagery-based motivational interviewing (MI) when treating people with diabetes-related foot disease (DFD), and to examine impacts on MI related skills, job satisfaction and subjective experiences in a mixed-methods pilot study. Methods Eleven recruited podiatrists (Median age 35, 9 female) received two 4-hour training sessions and three received later mentoring. MI and imagery skills were rated using validated tools during two clinical sessions per participant at baseline, and 2- and 12-weeks post-training. Job satisfaction was assessed at baseline and 12 weeks. Semi-structured interviews at 12 weeks were analysed using the framework approach. Results Significant improvements over time ( p =.006-.044) with substantial effect sizes (η 2 =.50-.67) were found in three of four global MI related communication skills and two of four MI behaviours. However, effects on these indices were not sustained to 12 weeks, and imagery was rarely used. Job satisfaction was high at baseline and unchanged at follow-up ( p =0.34, η 2 =.100). In qualitative interviews, MI training and skills were valued, but significant challenges in using MI when treating people with DFD were reported. Conclusion Training podiatrists in MI may have potential but more training, observation and mentoring appear needed to obtain sustained communication changes in practice.

Motivational Interviewing is a widely used counselling technique. A fundamental principle of this technique is that hearing oneself argue for change strengthens motivation. This study presents the first analysis of participants' dialogue with an automated motivational interviewer. The objective was to explore communication with, and perceptions of, a technology-delivered adaptation of motivational interviewing (TAMI) delivered by a pre-recorded video-counsellor. Eighteen participants undertook the video interview and evaluated it after one week. Interviews were scored for change and sustain talk. Participants' written evaluations were subjected to thematic analysis. Interviews lasted 10 min 30s (SD 3 min 0 s). Change talk was observed in a mean of 16 of 25 responses (SD 3.35, range 11–21). Sustain talk was less frequent (mean = 3.4 replies, SD = 2.5, range 0 to 8). Participants disliked seeing their own image in the webcam and desired a personalised interaction where each question depended on the answer given to the previous one. Positive appraisals included space to think about motivation and plans, and hearing themselves voicing goals. A brief, generic, automated TAMI elicited change talk and was perceived as motivating., Highlights • First test of a spoken motivational interview with a pre-recorded video-counsellor • Interview elicited considerably more ‘change talk’ than ‘sustain talk’. • Participants found it motivating to hear themselves voicing goals and plans aloud.

Introduction Applications or “mobile apps” are a potentially important source of assistance for serving and ex-serving Defence members with mental health problems. PTSD Coach Australia is a modified version of an application developed by the US Department of Veteran Affairs. Clinician perceptions of mobile apps are important as they influence the dissemination and adoption of apps. This study aimed to explore the perceptions of PTSD Coach Australia by clinicians with experience in assisting Defence members with mental health problems. Method The study involved two samples of participants who were asked about their perceptions of PTSD Coach Australia. The first involved 33 clinicians who participated in one of five focus groups. The second comprised 30 clinicians who were individually interviewed by telephone. Qualitative responses to questions regarding PTSD Coach Australia were analysed to identify representative themes. Participants in the focus group sample also rated the app on the user version of the Mobile Apps Rating Scale (uMARS). Results On the uMARS, clinicians rated the mobile app's subjective quality as ‘average’ to ‘good’. Participants generally saw the app as a useful to help track symptoms, improve engagement and help implement strategies between sessions. However, they also expressed concerns with the app not being user-friendly (e.g. too wordy, poor layout/navigation) and having technical issues (freezing or crashing on Android devices). Discussion PTSD Coach Australia is generally seen as being acceptable and useful by mental health clinicians. However, it is important to include their concerns in future developments of PTSD Coach Australia and similar mobile apps in order to maximize their utilisation in Defence members., Highlights • Mental health clinicians rated the PTSD Coach Australia mobile app’s subjective quality as ‘average’ to ‘good’. • Mental health clinicians believe that the app may help clients improve self-awareness and practice coping strategies. • Military apps should address clinician concerns about technical problems, aesthetics and utility for military personnel.

Background Young Australians (16-25 years) have the highest rates of past-month cannabis use in the world. Cannabis use increases the risk of alcohol and other drug disorders and depressive disorders, and has a robust dose-response association with psychotic experiences (PEs) and disorders. PEs are subthreshold positive psychotic symptoms, including delusions and hallucinations, which increase the risk of substance use, depressive or anxiety disorders, and psychotic disorders. Access to effective web-based early interventions targeting both cannabis use and PEs could reduce such risk in young people. Objective The objective of this study is to determine the efficacy and cost-effectiveness of the Keep it Real web-based program compared to an information-only control website among young cannabis users (16-25 years) with PEs. Methods Participants are recruited online, and consenting individuals meeting inclusion criteria (aged 16-25 years, who have used cannabis in the past month and experienced PEs in the past 3 months) are automatically randomized to either the Keep it Real web-based program (n=249) or an information-only control website (n=249). Both websites are self-guided (fully automated). The baseline and follow-up assessments at 3, 6, 9, and 12 months are self-completed online. Primary outcome measures are weekly cannabis use, PEs, and the relative cost-effectiveness for quality-adjusted life years. Secondary outcomes include other substance use and related problems, PE-related distress, cannabis intoxication experiences, severity of cannabis dependence, depression/anxiety symptoms, suicidality, and mental well-being and functioning. Results Recruitment commenced in February 2019, and the results are expected to be submitted for publication in mid-2021. Conclusions This study protocol describes a large randomized controlled trial of a new web-based program for young cannabis users experiencing PEs. If effective, the accessibility and scalability of Keep it Real could help reduce growing public health concerns about the significant social, economic, and health impacts of cannabis use. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12618001107213; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374800 International Registered Report Identifier (IRRID) DERR1-10.2196/15803

BACKGROUND Adolescence 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. OBJECTIVE We 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. METHODS A 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. RESULTS Young 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. CONCLUSIONS Niggle 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 and Aims Ravulizumab is a long-acting C5 inhibitor, derived from eculizumab, that is dosed every 8 weeks. Ravulizumab was approved in the United States for patients with atypical haemolytic uraemic syndrome (aHUS) and it is currently under evaluation in the EU based on the phase 3 trial (NCT02949128) efficacy and safety results at 26 weeks in patients with aHUS. Here, we report longer term efficacy and safety of ravulizumab obtained from the trial during the ongoing extension period. Method This phase 3 trial was a single arm, global, open label study in adults (≥18 years of age) with aHUS naïve to complement-inhibitor therapy. Ravulizumab was administered by intravenous infusion (IV) every 8 weeks during the maintenance phase. Patients fulfilling laboratory criteria for active TMA, ADAMTS13>5%, and negative STEC-HUS testing were eligible. Patients that completed the 26-week initial evaluation period could enter the extension period. The primary endpoint was complete TMA response (normalisation of platelet count and lactate dehydrogenase [LDH], and ≥ 25% improvement in serum creatinine from baseline, measured at 2 separate assessments obtained at least 28 days apart). Secondary endpoints included changes from baseline in haematological parameters, kidney function, and FACIT-fatigue scores. Treatment emergent adverse events were also evaluated. Here, interim cumulative data on primary and secondary endpoints through at least 52 weeks are reported. Results Forty-seven of 56 enrolled patients completed the initial evaluation period and received at least one dose of ravulizumab in the extension period. All patients achieved complete inhibition of terminal complement as demonstrated by sustained suppression of free-C5 ( Although three new SAEs were reported during the extension period, there were no further fatal adverse events. As in the primary analysis period, no meningococcal infections occurred through the last patient follow-up. Conclusion In the extension period of the phase 3 trial, ravulizumab continued to have a good benefit: risk profile. At last follow-up, the cumulative efficacy of ravulizumab to treat complement mediated TMA in patients with aHUS improved to 61% from 54% in the initial evaluation period. Most AEs occurred in the first 26 weeks, and there were no meningococcal infections identified in the study. These results suggest that with ravulizumab further improvement in efficacy is possible with longer treatment with no compromise in safety and improved convenience of 8-week dosing intervals.

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.

Pregnancy and postpartum are high-risk periods for different forms of thrombotic microangiopathy (TMA). However, the management of pregnancy-associated TMA remains ill defined. This report, by an international multidisciplinary working group of obstetricians, nephrologists, hematologists, intensivists, neonatologists, and complement biologists, summarizes the current knowledge of these potentially severe disorders and proposes a practical clinical approach to diagnose and manage an episode of pregnancy-associated TMA. This approach takes into account the timing of TMA in pregnancy or postpartum, coexisting symptoms, first-line laboratory workup, and probability-based assessment of possible causes of pregnancy-associated TMA. Its aims are: to rule thrombotic thrombocytopenic purpura (TTP) in or out, with urgency, using ADAMTS13 activity testing; to consider alternative disorders with features of TMA (preeclampsia/eclampsia; hemolysis elevated liver enzymes low platelets syndrome; antiphospholipid syndrome); or, ultimately, to diagnose complement-mediated atypical hemolytic uremic syndrome (aHUS; a diagnosis of exclusion). Although they are rare, diagnosing TTP and aHUS associated with pregnancy, and postpartum, is paramount as both require urgent specific treatment.

Ravulizumab is a long-acting C5 inhibitor engineered from eculizumab with increased elimination half-life, allowing an extended dosing interval from two to eight weeks. Here we evaluate the efficacy and safety of ravulizumab in adults with atypical hemolytic uremic syndrome presenting with thrombotic microangiopathy. In this global, phase 3, single arm study in complement inhibitor-naive adults (18 years and older) who fulfilled diagnostic criteria for atypical hemolytic uremic syndrome, enrolled patients received ravulizumab through a 26-week initial evaluation period. The primary endpoint was complete thrombotic microangiopathy response defined as normalization of platelet count and lactate dehydrogenase and 25% or more improvement in serum creatinine. Secondary endpoints included changes in hematologic variables and renal function. Safety was also evaluated. Ravulizumab treatment resulted in an immediate, complete, and sustained C5 inhibition in all patients. Complete thrombotic microangiopathy response was achieved in 53.6% of patients. Normalization of platelet count, lactate dehydrogenase and 25% or more improvement in serum creatinine was achieved in 83.9%, 76.8% and 58.9% of patients, respectively. Improvement in estimated glomerular filtration rate by one or more stage was achieved in 68.1% of patients by day 183. No unexpected adverse events were reported across a safety analysis set of 58 patients. Four deaths occurred (three within one month of study initiation, including one in a patient excluded based on eligibility criteria after the first dose) with none considered treatment-related by the study investigator. Thus, treatment with ravulizumab once every eight weeks resulted in rapidly improved hematologic and renal endpoints with no unexpected adverse events in adults with atypical hemolytic uremic syndrome.

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

Background The research explored parents' role constructions for themselves and other caregivers in promoting physical activity, limiting screen time, and ensuring their young child is not sedentary or restrained for extended periods. Method Using a qualitative social constructionist epistemological position, 10 mothers and 10 fathers (aged 22–49 years) from different households in South East Queensland, Australia, were interviewed. The interviews were transcribed verbatim and analysed using thematic analysis. Results Thirteen themes emerged in parents' descriptions of their role, aligning with three of the four key influences on parents' role constructions for involvement in their child's behaviour: beliefs about desired child outcomes, beliefs about who is responsible for the outcomes, and parental behaviours related to the beliefs and expectations. Conclusions Current findings indicate that parents commonly describe active manifestations of parent role constructions that are conducive to facilitating childhood physical activity‐related behaviours. Because many young Australian children are still not sufficiently active, future interventions should seek to target processes influencing parents' ability to fulfil their constructed roles and translate them into actions, including knowledge and skills, self‐efficacy for helping their child, and developing the ability to manage the mix of demands on their time.

Functional imagery training (FIT) extends multisensory imagery training by involving athletes with goal setting and appraisal. The authors measured the effect of FIT on 24 professional soccer players’ grit, a personality trait associated with perseverance for a long-term goal. In a stepped-wedge design, an immediate (n = 9) and a delayed (n = 10) group received FIT at Week 1 or 6 and were measured at Week 12. A self-selected control group (n = 5) received no intervention. The delayed group was also measured at Week 6 just before their intervention, and at Week 18. Grit scores in both intervention groups increased after the intervention, but the control group’s did not. The delayed group increased in grit between Weeks 6 and 12, showing the effectiveness of the intervention over a relatively short time, and continued to improve to Week 18. In the intervention groups, vividness of goal imagery also increased and players perceived that FIT improved sport performance.

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 Ravulizumab, a humanized anti-complement C5 monoclonal antibody designed by targeted modification of eculizumab to achieve an extended half-life, is approved to treat aHUS in the USA (2019), EU and Japan (2020). Data at 26 weeks (wk) and 1 year (yr) from the phase 3 studies of ravulizumab in adults and children with aHUS have been published. Here we report 2-yr data from these trials. Methods Efficacy and safety data from ravulizumab clinical trials in adults naïve to complement inhibitor treatment (NCT02949128), and in children either naïve to (naïve) or switched from (switch) eculizumab (NCT03131219), were assessed at 2 yr and presented alongside data from the initial 26-wk evaluation periods; patients were dosed every 8 wk (adult), or every 4 or 8 wk (children), according to body weight. Descriptive statistical analyses were conducted on these data. No statistical comparisons between data at 26 wk and 2 yr, or between trials, were conducted. Results Efficacy data in adults and treatment-naïve children are presented in the Table. Complete thrombotic microangiopathy (TMA) response (platelet count normalization, lactate dehydrogenase normalization, and ≥25% improvement in serum creatinine from baseline, met concurrently at 2 separate assessments, at least 4 wk apart) was achieved in more patients at 2 yr vs 26 wk in both studies (adult: 34 [61%) vs 30 [54%]; naïve: 18 [90%] vs 15 [75%]). All complete TMA response components were either numerically improved or maintained at 2 yr vs 26 wk. Kidney function continued to improve, with the median change in estimated glomerular filtration rate from baseline numerically increasing at 2 yr vs 26 wk in both adults (35 vs 29 mL/min/1.73m 2) and naïve children (82.5 vs 80 mL/min/1.73m 2). Most patients receiving dialysis at baseline were able to discontinue dialysis at 26 wk; this was sustained in adults (67% vs 67%) while all naïve children receiving dialysis at baseline had discontinued by 2 yr (83% vs 100%). No patients who discontinued dialysis by 26 wk subsequently restarted. Chronic kidney disease (CKD) stage improved in most patients through 26 wk in both studies (adult, 68%; naïve, 88%); improvements were sustained at 2 yr (adult, 71%; naïve, 94%). No naïve children experienced a worsening of CKD stage at 2 yr. Improvements from baseline in quality of life were seen at both 26 wk and 2 yr, as measured by Functional Assessment of Chronic Illness Therapy-Fatigue (adults: 20 vs 12; naïve: 10 vs 8), EQ-5D-3L visual analog scale (adults: 32 vs 33) and EQ-5D-3L time trade-off (adults: 0.32 vs 0.31). Most adverse events (AEs) and serious AEs (SAEs) occurring in these studies were reported during the initial 26-wk evaluation period, with a general reduction in the number of patients with any new S/AE events being reported at 2 yr. The most common AEs reported through 2 yr, which had not met the 15% reporting threshold through 26 wk, were (n, %): adults - constipation (9, 16%), fatigue (9, 16%) and nasopharyngitis (9, 16%); naïve children - abdominal pain (6, 25%), contusion (5, 21%), cough (5, 21%), nausea (4, 17%), myalgia (4, 17%), rash (4, 17%) and rhinorrhea (4, 17%); switch children - upper respiratory tract infections (URTI; 4, 40%), oropharyngeal pain (3, 30%), pharyngitis (3, 30%), cough (2, 20%), gastroenteritis (2, 20%), nasopharyngitis (2, 20%), otitis media (2, 20%), viral URTI (2, 20%) and dehydration (2, 20%). No patients discontinued either study due to treatment-emergent AEs after 26 wk. No meningococcal infections were recorded in either study at any timepoints. One adult patient, who had previously met complete TMA response criteria while receiving therapy, discontinued treatment by choice and subsequently experienced recurrent disease, as evidenced by an increase in serum creatinine (SCr). This patient then restarted therapy, leading to improvements in SCr levels. Conclusions In both treatment-naïve adults and children, ravulizumab was associated with numerically sustained or increased improvements in hematologic outcomes and kidney function at 2 yr vs 26 wk. Fewer S/AEs were reported during the extension period of these studies vs the initial 26-wk evaluation periods. Importantly, no meningococcal infections were reported in either study at any timepoint. The data suggest that long-term treatment with ravulizumab is well tolerated and may be associated with continuing improvements in TMA parameters and renal function in adults and children with aHUS. Figure 1 Figure 1. Disclosures Dixon: Apellis Pharmaceuticals: Consultancy; Horizon Pharmaceuticals: Consultancy; Alexion Pharmaceuticals: Consultancy. Kavanagh: Gyroscope Therapeutics: Current equity holder in publicly-traded company, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Apellis: Honoraria, Speakers Bureau; Idorsia: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Alexion Pharmaceuticals: Honoraria, Speakers Bureau. Kang: Alexion Pharmaceuticals: Honoraria, Research Funding; Handok: Honoraria; Kyowa Kirin: Honoraria, Research Funding; Amgen: Research Funding; Bayer: Research Funding. Wang: Alexion, AstraZeneca Rare Disease Inc.: Current Employment. Garlo: Alexion: Current Employment; AstraZeneca: Current Employment. Greenbaum: Alexion Pharmaceuticals: Honoraria, Research Funding. Ogawa: Alexion Pharmaceuticals: Current Employment. Cataland: Ablynx/Sanofi: Consultancy, Research Funding; Sanofi Genzyme: Consultancy; Alexion: Consultancy, Research Funding; Takeda: Consultancy. Miyakawa: Sanofi: Consultancy; Zenyaku Kogyo: Consultancy; Sanofi: Research Funding; argenx: Consultancy, Research Funding.

This paper reports the design and qualitative evaluation of a social robot programmed to deliver a talk-based treatment program to improve health behaviour change for food intake and weight loss. A qualitative study was conducted to investigate factors that influenced human-robot interaction and its relationship to health treatment outcomes. Semi-structured interviews were undertaken on completion of a randomised controlled trial that used an autonomous robot to deliver a 4-week behavioral intervention to help coach people to decrease the consumption of high calorie foods. Questions focused on individuals’ preferences, learnings and outcomes from their participation in the trial. Twenty participants completed the treatment, and 18 conducted an interview. Content analysis found that a social robot to deliver a psychotherapeutic treatment was effective and feasible. Participants did make changes to their health behaviour change with a >50% reduction in high calorie intake and average reduction of 4.4 kilograms in weight loss. The robot received positive evaluations on its interactive nature and sociable persona. Most participants made improvements that were aligned with their chosen health goal after completing the robot-delivered sessions, and reported that the robot sessions helped them to achieve their behaviour change goals, such as consuming fewer high calorie foods. Detailed recommendations are provided for the future design of healthcare interventions by robots, including key considerations for robot behaviour, treatment content, and presentation of the program. Future recommendations are presented for the development of robot personalization to more closely resemble techniques and skills from client-centred counselling.