Cost-utility analysis of adjunct repetitive transcranial magnetic stimulation for treatment resistant bipolar depression.

OBJECTIVE: To evaluate the cost-effectiveness of repetitive transcranial magnetic stimulation (rTMS) as an adjunct to standard care from an Australian health sector perspective, compared to standard care alone for adults with treatment-resistant bipolar depression (TRBD). METHODS: An economic model was developed to estimate the cost per disability-adjusted life-year (DALY) averted and quality-adjusted life-year (QALY) gained for rTMS added to standard care compared to standard care alone, for adults with TRBD. The model simulated the time in three health states (mania, depression, residual) over one year. Response to rTMS was sourced from a meta-analysis, converted to a relative risk and used to modify the time in the depressed state. Uncertainty and sensitivity tested the robustness of results. RESULTS: Base-case incremental cost-effectiveness ratios (ICERs) were $72,299 per DALY averted (95 % Uncertainty Interval (UI): $60,915 to $86,668) and $46,623 per QALY gained (95 % UI: $39,676 - $55,161). At a willingness to pay (WTP) threshold of $96,000 per DALY averted, the base-case had a 100 % probability of being marginally cost-effective. At a WTP threshold of $64,000 per QALY gained, the base-case had a 100 % probability of being cost-effective. Sensitivity analyses decreasing the number of sessions provided, increasing the disability weight or the time spent in the depression state for standard care improved the ICERs for rTMS. CONCLUSIONS: Dependent on the outcome measure utilised and assumptions, rTMS would be considered a very cost-effective or marginally cost-effective adjunct to standard care for TRBD compared to standard care alone.

Age at first drink and its influence on alcohol use behaviours in young adulthood: Evidence from an Australian household-based panel study.

BACKGROUND: Public health guidelines recommend delaying the initiation age for alcohol. However, the causal link between age-at-first-drink (AFD) and future alcohol use in young adulthood is uncertain. This study examined the association between AFD and alcohol-related outcomes at age 20 years using an Australian sample. METHODS: Data were obtained from Waves 1-19 (years 2001-2019) of the Household, Income and Labour Dynamics in Australia Survey on 20-year-olds with responses across ≥3 consecutive waves (n = 2278). The AFD for each respondent (between 15 and 20 years) was analysed relative to Australian legal drinking age (18 years). Inverse probability treatment weighting was used to evaluate associations between AFD and four outcomes at age 20 years: risk of current alcohol use; quantity of weekly alcohol consumption; risk of binge drinking; and frequency of binge drinking. Adjustments were made for confounders (e.g., heavy drinking by parents). Robustness of study findings was evaluated using several diagnostic tests/sensitivity analyses. RESULTS: Among 20-year-olds, those with an AFD of 15-16 years consumed significantly more alcohol per week compared to an AFD of 18 years. Additionally, 20-year-old drinkers with an AFD of 16 years were significantly more likely to binge drink (though this association was likely confounded). An inverse dose-response relationship was observed between AFD and weekly alcohol consumption at 20 years, where a higher AFD led to lower alcohol consumption. CONCLUSION: Study findings indicate an association between a higher AFD and consuming less alcohol in young adulthood, which could potentially support the scale-up of prevention programs to delay AFD among Australian adolescents.

Health service and medication costs associated with common mental disorders and subthreshold symptoms in women: Findings from the Geelong Osteoporosis Study in Australia.

OBJECTIVE: This analysis estimated 2013 annual healthcare costs associated with the common mental disorders of mood and anxiety disorders and psychological symptoms within a representative sample of Australian women. METHODS: Data from the 15-year follow-up of women in the Geelong Osteoporosis Study were linked to 12-month Medicare Benefits Schedule and Pharmaceutical Benefits Scheme data. A Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Non-patient edition identified common mental disorders and the General Health Questionnaire 12 assessed psychological symptoms. Participants were categorised into mutually exclusive groups: (1) common mental disorder (past 12 months), (2) subthreshold (no common mental disorder and General Health Questionnaire 12 score ⩾4) or (3) no common mental disorder and General Health Questionnaire 12 score <4. Two-part and hurdle models estimated differences in service use, and adjusted generalised linear models estimated mean differences in costs between groups. RESULTS: Compared to no common mental disorder, women with common mental disorders utilised more Medicare Benefits Schedule services (mean 26.9 vs 20.0, p < 0.001), had higher total Medicare Benefits Schedule cost ($1889 vs $1305, p < 0.01), received more Pharmaceutical Benefits Scheme prescriptions (35.8 vs 20.6, p < 0.001), had higher total Pharmaceutical Benefits Scheme cost ($1226 vs $740, p < 0.05) and had significantly higher annual out-of-pocket costs for Pharmaceutical Benefits Scheme prescriptions ($249 vs $162, p < 0.001). Compared to no common mental disorder, subthreshold women were less likely to use any Medicare Benefits Schedule service (89.6% vs 97.0%, p < 0.01), but more likely to use mental health services (11.4% vs 2.9%, p < 0.01). The subthreshold group received more Pharmaceutical Benefits Scheme prescriptions (mean 43.3 vs 20.6, p < 0.001) and incurred higher total Pharmaceutical Benefits Scheme cost ($1268 vs $740, p < .05) compared to no common mental disorder. CONCLUSIONS: Common mental disorders and subthreshold psychological symptoms place a substantial economic burden on Australian healthcare services and consumers.

Health Service Utilisation of People Living with Psychosis: Validity of Self-report Compared with Administrative Data in a Randomised Controlled Trial.

BACKGROUND: Self-reported service use informs resource utilisation and cost estimates, though its validity for use within economic evaluations is uncertain. OBJECTIVE: The aim of this study is to assess agreement in health resource-use measurement between self-reported and administrative data across different resource categories, over time and between different recall periods by subgroups among Australians living with psychosis. METHODS: Data were obtained for 104 participants with psychotic disorders from a randomised controlled trial. Agreement between self-reported resource-use questionnaires and administrative data on community-based services and medication use was assessed through estimating differences of group mean number of visits and medications used and intraclass correlation coefficients (ICC) over multiple time periods. RESULTS: ICC showed moderate agreement across most time periods for general practitioners, psychiatrists and mental health medications. No clear trends were discernible over time, between varying lengths of recall periods nor across participant subgroups. CONCLUSION: Despite poor agreement, when measuring visits to psychologists and other health professionals, small overall differences in group mean number of visits indicate that self-reported data may still be valid for use in economic evaluations in people living with psychosis.

Ensuring the affordable becomes accessible-lessons from ketamine, a new treatment for severe depression.

In this paper, the case study of ketamine as a new treatment for severe depression is used to outline the challenges of repurposing established medicines and we suggest potential solutions. The antidepressant effects of generic racemic ketamine were identified over 20 years ago, but there were insufficient incentives for commercial entities to pursue its registration, or support for non-commercial entities to fill this gap. As a result, the evaluation of generic ketamine was delayed, piecemeal, uncoordinated, and insufficient to gain approval. Meanwhile, substantial commercial investment enabled the widespread registration of a patented, intranasal s-enantiomeric ketamine formulation (Spravato®) for depression. However, Spravato is priced at $600-$900/dose compared to ~$5/dose for generic ketamine, and the ~AUD$100 million annual government investment requested in Australia (to cover drug costs alone) has been rejected twice, leaving this treatment largely inaccessible for Australian patients 2 years after Therapeutic Goods Administration approval. Moreover, emerging evidence indicates that generic racemic ketamine is at least as effective as Spravato, but no comparative trials were required for regulatory approval and have not been conducted. Without action, this story will repeat regularly in the next decade with a new wave of psychedelic-assisted psychotherapy treatments, for which the original off-patent molecules could be available at low-cost and reduce the overall cost of treatment. Several systemic reforms are required to ensure that affordable, effective options become accessible; these include commercial incentives, public and public-private funding schemes, reduced regulatory barriers and more coordinated international public funding schemes to support translational research.

Economic evaluations of alcohol pharmacotherapy: Systematic review of economic evaluations of pharmacotherapy for the treatment of alcohol use disorder.

OBJECTIVE: Alcohol use disorders confer a significant burden of disease and economic cost worldwide. However, the utilisation of pharmacotherapies to manage alcohol use disorder is poor. We aimed to conduct a systematic review of economic evaluation studies of alcohol use disorder pharmacotherapies. METHODS: A search was conducted in Embase, Medline, CINAHL, PsychINFO and EconLit (August 2019, updated September 2022). Full economic evaluations using pharmacotherapy to treat alcohol use disorders were included. Included studies were stratified by medication and summarised descriptively. The Consensus on Health Economic Criteria list was used to assess the methodological quality. RESULTS: A total of 1139 studies were retrieved, of which 15 met the inclusion criteria. All studies were conducted in high-income countries. Four studies analysed nalmefene, four studies assessed acamprosate, three for naltrexone and four for stand-alone and/or combinations of naltrexone and acamprosate. There were 21 interventions synthesised from 15 studies as some studies evaluated multiple interventions and comparators. More than half of the included studies (73%) reported pharmacotherapy as dominant (less costly and more effective than comparators). From healthcare payer perspectives, five studies found that pharmacotherapy added to psychosocial support was dominant or cost-effective, accruing additional benefits at a higher cost but under accepted willingness to pay thresholds. Three analyses from a societal perspective found pharmacotherapy added to psychosocial support was a dominant or cost-effective strategy. Quality scores ranged from 63% to 95%. CONCLUSION: Pharmacotherapy added to psychosocial support was cost-effective from both healthcare and societal perspectives, emphasising an increased role for pharmacotherapy to reduce the burden of alcohol use disorders.

Economic evidence for prevention and treatment of eating disorders: An updated systematic review.

OBJECTIVE: This systematic review updates an existing review examining the cost-effectiveness of interventions to prevent and treat eating disorders (EDs). METHOD: Literature search was conducted in Academic Search Complete, MEDLINE, CINAHL, PsycINFO, EconLit, Global Health, ERIC, Health Business Elite, and Health Policy Reference Center electronic databases, capturing studies published between March 2017 to April 2023. Hand-searching was conducted as supplementary including gray literature search. Included articles were (1) full economic evaluations or return-on-investment studies, (2) in English and (3) aimed at prevention and treatment of any ED. Included studies were added and synthesized with previously reviewed studies. Screening and extraction followed PRISMA guidelines. Quality assessment was conducted using the Drummond checklist. PROSPERO registration CRD42021287464. RESULTS: A total of 28 studies were identified, including 15 published after the previous review. There were nine prevention, seven anorexia nervosa (AN) treatment, five bulimia nervosa (BN) treatment, four binge-eating disorder (BED), and three non-specific ED treatment studies. Findings indicate value-for-money evidence supporting all interventions. Quality assessment showed studies were fair-to-good quality. DISCUSSION: There has been significant growth in cost-effectiveness studies over the last 5 years. Findings suggest that interventions to prevent and treat ED offer value for money. Interventions such as Featback (ED prevention and non-specific ED treatment); focal psychodynamic therapy, enhanced cognitive behavioral therapy, and high-calorie refeeding (AN treatment); stepped-care with assisted self-help and internet-based cognitive behavioral therapy (BN treatment); and cognitive behavioral therapy guided self-help intervention (BED treatment) have good quality economic evidence. Further research in implementation of interventions is required. PUBLIC SIGNIFICANCE STATEMENT: The increasing prevalence of ED globally has significant impact on healthcare systems, families, and society. This review is showcasing the value for money of interventions of eating disorders prevention and treatment. This review found that existing interventions offers positive economic benefit for the healthcare system.

OBJETIVO: Esta revisión sistemática actualiza una revisión existente que examina la rentabilidad de las intervenciones para prevenir y tratar los trastornos de la conducta alimentaria (TCA). MÉTODO: Se realizó una búsqueda bibliográfica en las bases de datos electrónicas Academic Search Complete, MEDLINE, CINAHL, PsycINFO, EconLit, Global Health, ERIC, Health Business Elite y Health Policy Reference Center, abarcando estudios publicados entre marzo de 2017 y abril de 2023. Se realizó una búsqueda manual como complemento, incluyendo la búsqueda de literatura gris. Los artículos incluidos eran (1) evaluaciones económicas completas o estudios de retorno de inversión, (2) en inglés y (3) dirigidos a la prevención y tratamiento de cualquier TCA. Los estudios incluidos se añadieron y sintetizaron con estudios previamente revisados. El cribado y la extracción siguieron las pautas PRISMA. La evaluación de la calidad se realizó utilizando la lista de verificación de Drummond. Registro en PROSPERO CRD42021287464. RESULTADOS: Se identificaron 28 estudios, incluyendo 15 publicados después de la revisión anterior. Hubo nueve estudios de prevención, siete de tratamiento de anorexia nerviosa (AN), cinco de tratamiento de bulimia nerviosa (BN), cuatro de trastorno por atracón (TpA) y tres de tratamiento de TCA no especificados. Los hallazgos indican evidencia de valor por dinero que respalda todas las intervenciones. La evaluación de la calidad mostró que los estudios eran de calidad aceptable a buena. DISCUSIÓN: Ha habido un crecimiento significativo en los estudios de rentabilidad en los últimos cinco años. Los hallazgos sugieren que las intervenciones para prevenir y tratar los TCA ofrecen valor por dinero. Intervenciones como Featback (prevención de TCA y tratamiento de TCA no específicos); terapia psicodinámica focal, terapia cognitivo-conductual mejorada y rehabilitación nutricional con alto contenido calórico (tratamiento de AN); atención escalonada con autoayuda asistida y terapia cognitivo-conductual en línea (tratamiento de BN); y terapia cognitivo-conductual guiada de autoayuda (tratamiento de TpA) tienen una buena evidencia económica de calidad. Se requiere más investigación en la implementación de intervenciones.

Randomised controlled trial of neurostimulation for symptoms of anorexia nervosa (TRENA study): study protocol.

BACKGROUND: Anorexia nervosa (AN) has amongst the highest mortality rates and the highest treatment costs of any psychiatric disorder. Recently, interest in non-invasive brain stimulation as a novel treatment for AN has grown. These include repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). METHODS: This double-blind, randomised sham-controlled trial will compare the relative acceptability and efficacy of tDCS and rTMS in people with AN. 70 participants will be randomised to active or sham tDCS, or active or sham rTMS treatment (2:1:2:1 ratio) over an 8-week treatment period. Participants will receive treatment as usual across the study duration. The primary outcomes are change on the Eating Disorder Examination Questionnaire and treatment acceptability. Secondary outcomes will include change in weight, cognition, mood, interpersonal functioning, and quality of life. Following the 8-week assessment, all participants will have the option of receiving an additional 12 weeks of at-home tDCS. A follow-up assessment will be conducted at 20 weeks post treatment. DISCUSSION: Research into non-invasive brain stimulation as treatments for AN has potential to improve clinical outcomes for patients by comparing the relative efficacy and acceptability of both treatment modalities in the inpatient and at-home setting (i.e., for at-home tDCS) results from this study will provide important information for informing future larger clinical trials of these treatments for AN. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05788042.

Efficacy and safety of a 4-week course of repeated subcutaneous ketamine injections for treatment-resistant depression (KADS study): randomised double-blind active-controlled trial.

BACKGROUND: Prior trials suggest that intravenous racemic ketamine is a highly effective for treatment-resistant depression (TRD), but phase 3 trials of racemic ketamine are needed. AIMS: To assess the acute efficacy and safety of a 4-week course of subcutaneous racemic ketamine in participants with TRD. Trial registration: ACTRN12616001096448 at www.anzctr.org.au. METHOD: This phase 3, double-blind, randomised, active-controlled multicentre trial was conducted at seven mood disorders centres in Australia and New Zealand. Participants received twice-weekly subcutaneous racemic ketamine or midazolam for 4 weeks. Initially, the trial tested fixed-dose ketamine 0.5 mg/kg versus midazolam 0.025 mg/kg (cohort 1). Dosing was revised, after a Data Safety Monitoring Board recommendation, to flexible-dose ketamine 0.5-0.9 mg/kg or midazolam 0.025-0.045 mg/kg, with response-guided dosing increments (cohort 2). The primary outcome was remission (Montgomery-Åsberg Rating Scale for Depression score ≤10) at the end of week 4. RESULTS: The final analysis (those who received at least one treatment) comprised 68 in cohort 1 (fixed-dose), 106 in cohort 2 (flexible-dose). Ketamine was more efficacious than midazolam in cohort 2 (remission rate 19.6% v. 2.0%; OR = 12.1, 95% CI 2.1-69.2, P = 0.005), but not different in cohort 1 (remission rate 6.3% v. 8.8%; OR = 1.3, 95% CI 0.2-8.2, P = 0.76). Ketamine was well tolerated. Acute adverse effects (psychotomimetic, blood pressure increases) resolved within 2 h. CONCLUSIONS: Adequately dosed subcutaneous racemic ketamine was efficacious and safe in treating TRD over a 4-week treatment period. The subcutaneous route is practical and feasible.

A systematic review of economic evaluations for opioid misuse, cannabis and illicit drug use prevention.

BACKGROUND: Substance use disorders negatively affect global disease burden. Effective preventive interventions are available, but whether they provide value for money is unclear. AIMS: This review looks at the cost-effectiveness evidence of preventive interventions for cannabis use, opioid misuse and illicit drug use. METHOD: Literature search was undertaken in Medline, CINAHL, PsycINFO, EconLit through EBSCOhost and EMBASE, up to May 2021. Grey literature search was conducted as supplement. Studies included were full economic evaluations or return-on-investment (ROI) analyses for preventing opioid misuse, cannabis and illicit drug use. English-language restriction was used. Outcomes extracted were incremental cost-effectiveness ratios (ICER) or ROI ratios, with costs presented in 2019 United States dollars. Quality was assessed with the Drummond checklist. RESULTS: Eleven full economic evaluation studies were identified from 5674 citations, with all studies conducted in high-income countries. Most aimed to prevent opioid misuse (n = 4), cannabis (n = 3) or illicit drug use (n = 5). Modelling was the predominant methodology (n = 7). Five evaluated school-based universal interventions targeting children and adolescents (aged <18 years). Five cost-benefit studies reported cost-savings. One cost-effectiveness and two cost-utility analysis studies supported the cost-effectiveness of interventions, as ICERs fell under prespecified value-for-money thresholds. CONCLUSIONS: There are limited economic evaluations of preventive interventions for opioid misuse, cannabis and illicit drug use. Family-based intervention (ParentCorps), school-based interventions (Social and Emotional Training and Project ALERT) and a doctor's programme to assess patient risk of misusing narcotics ('the Network System to Prevent Doctor-Shopping for Narcotics') show promising cost-effectiveness and warrant consideration.

Interventions to prevent alcohol use: systematic review of economic evaluations.

BACKGROUND: Alcohol use is a leading risk factor for death and disability worldwide. AIMS: We conducted a systematic review on the cost-effectiveness evidence for interventions to prevent alcohol use across the lifespan. METHOD: Electronic databases (EMBASE, Medline, PsycINFO, CINAHL and EconLit) were searched for full economic evaluations and return-on-investment studies of alcohol prevention interventions published up to May 2021. The methods and results of included studies were evaluated with narrative synthesis, and study quality was assessed by the Drummond ten-point checklist. RESULTS: A total of 69 studies met the inclusion criteria for a full economic evaluation or return-on-investment study. Most studies targeted adults or a combination of age groups, seven studies comprised children/adolescents and one involved older adults. Half of the studies found that alcohol prevention interventions are cost-saving (i.e. more effective and less costly than the comparator). This was especially true for universal prevention interventions designed to restrict exposure to alcohol through taxation or advertising bans; and selective/indicated prevention interventions, which involve screening with or without brief intervention for at-risk adults. School-based interventions combined with parent/carer interventions were cost-effective in preventing alcohol use among those aged under 18 years. No interventions were cost-effective for preventing alcohol use in older adults. CONCLUSIONS: Alcohol prevention interventions show promising evidence of cost-effectiveness. Further economic analyses are needed to facilitate policy-making in low- and middle-income countries, and among child, adolescent and older adult populations.

The association between outpatient continuation/maintenance electroconvulsive therapy, readmission risk and total direct cost in patients with depressive, bipolar and psychotic disorders: A naturalistic retrospective cohort study.

BACKGROUND: The transdiagnostic effect of continuation/maintenance ECT (CM-ECT) across mood and psychotic disorders on hospital psychiatric readmission risk and total direct cost remains unclear. METHODS: A naturalistic retrospective analysis of 540 patients who received inpatient acute ECT treatment from May 2017 to Mar 2021 in a tertiary psychiatric institution. Patients were assessed with validated clinical rating scales pre-ECT and after the first 6 treatments of a course of inpatient acute ECT. After discharge, patients who continued with CM-ECT were compared with those not receiving CM-ECT using survival analysis of hospital readmission. Total direct cost (hospitalisation and ECT treatment cost) was also analysed. All patients were subjected to a standard post-discharge monitoring program with case managers checking in on the patients regularly after discharge and ensuring they were given an outpatient appointment within a month of discharge. RESULTS: Both cohorts had significant improvement in their rating scales scores after their first six 6 sessions of inpatient acute ECT. Patients who continued with CM-ECT after completing their inpatient acute ECT (mean number of acute ECT: N = 9.9, SD 5.3), had a significantly lower risk of readmission [adjusted hazard ratio of 0.68 (95 % CI: 0.49-0.94, p = 0.020)]. Patients who received CM-ECT also had a significantly lower average total direct cost compared to those who did not (SGD$35,259 vs SGD$61,337). For patients with mood disorders, the CM-ECT group had a significantly lower inpatient ECT cost, hospitalisation cost and total direct costs compared to those without CM-ECT. LIMITATIONS: The naturalistic study cannot prove a causal relationship between CM-ECT and reduced readmission and lower healthcare costs. CONCLUSION: CM-ECT is associated with lower readmission risks and lower total direct healthcare costs for the treatment of mood and psychotic disorders, especially for mood disorders.

Low-Intensity mental health Support via a Telehealth Enabled Network for adults with diabetes (LISTEN): protocol for a hybrid type 1 effectiveness implementation trial.

BACKGROUND: Mental health problems are common among people with diabetes. However, evidence-based strategies for the prevention and early intervention of emotional problems in people with diabetes are lacking. Our aim is to assess the real-world effectiveness, cost-effectiveness, and implementation of a Low-Intensity mental health Support via a Telehealth Enabled Network (LISTEN), facilitated by diabetes health professionals (HPs). METHODS: A hybrid type I effectiveness-implementation trial, including a two-arm parallel randomised controlled trial, alongside mixed methods process evaluation. Recruited primarily via the National Diabetes Services Scheme, Australian adults with diabetes (N = 454) will be eligible if they are experiencing elevated diabetes distress. Participants are randomised (1:1 ratio) to LISTEN-a brief, low-intensity mental health support program based on a problem-solving therapy framework and delivered via telehealth (intervention) or usual care (web-based resources about diabetes and emotional health). Data are collected via online assessments at baseline (T0), 8 weeks (T1) and 6 months (T2, primary endpoint) follow-up. The primary outcome is between-group differences in diabetes distress at T2. Secondary outcomes include the immediate (T1) and longer-term (T2) effect of the intervention on psychological distress, general emotional well-being, and coping self-efficacy. A within-trial economic evaluation will be conducted. Implementation outcomes will be assessed using mixed methods, according to the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. Data collection will include qualitative interviews and field notes. DISCUSSION: It is anticipated that LISTEN will reduce diabetes distress among adults with diabetes. The pragmatic trial results will determine whether LISTEN is effective, cost-effective, and should be implemented at scale. Qualitative findings will be used to refine the intervention and implementation strategies as required. TRIAL REGISTRATION: This trial has been registered with the Australian New Zealand Clinical Trials Registry (ACTRN: ACTRN12622000168752) on 1 February, 2022.

The PRESIDE (PhaRmacogEnomicS In DEpression) Trial: a double-blind randomised controlled trial of pharmacogenomic-informed prescribing of antidepressants on depression outcomes in patients with major depressive disorder in primary care.

BACKGROUND: The evidence for the clinical utility of pharmacogenomic (PGx) testing is growing, and guidelines exist for the use of PGx testing to inform prescribing of 13 antidepressants. Although previous randomised controlled trials of PGx testing for antidepressant prescribing have shown an association with remission of depression in clinical psychiatric settings, few trials have focused on the primary care setting, where most antidepressant prescribing occurs. METHODS: The PRESIDE Trial is a stratified double-blinded randomised controlled superiority trial that aims to evaluate the impact of a PGx-informed antidepressant prescribing report (compared with standard prescribing using the Australian Therapeutic Guidelines) on depressive symptoms after 12 weeks, when delivered in primary care. Six hundred seventy-two patients aged 18-65 years of general practitioners (GPs) in Victoria with moderate to severe depressive symptoms, measured using the Patient Health Questionnaire-9 (PHQ-9), will be randomly allocated 1:1 to each arm using a computer-generated sequence. Participants and GPs will be blinded to the study arm. The primary outcome is a difference between arms in the change of depressive symptoms, measured using the PHQ-9 after 12 weeks. Secondary outcomes include a difference between the arms in change in PHQ-9 score at 4, 8 and 26 weeks, proportion in remission at 12 weeks, a change in side effect profile of antidepressant medications, adherence to antidepressant medications, change in quality of life and cost-effectiveness of the intervention. DISCUSSION: This trial will provide evidence as to whether PGx-informed antidepressant prescribing is clinically efficacious and cost-effective. It will inform national and international policy and guidelines about the use of PGx to select antidepressants for people with moderate to severe depressive symptoms presenting in primary care. TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry ACTRN12621000181808. Registered on 22 February 2021.

Economic consequences of injury in female Australian footballers: A prospective observational study of emergency department presentations.

OBJECTIVE: Investigate the economic consequences of injuries to female Australian footballers from a health sector and societal perspective. METHODS: This prospective observational study invited 242 females to complete an online questionnaire 3-6 months following an Australian football injury which involved presentation to an ED in Victoria, Australia. The questionnaire inquired regarding healthcare use, time off work, return to playing football and extent of recovery following injury. Relevant information was also extracted from respondents' medical records regarding injury-type, body part injured, investigations and treatments. Healthcare costs were determined for each respondent's ED presentation, hospital admission/s (when relevant), and subsequent healthcare use. Societal costs were determined as lost income to the respondent and/or carer. RESULTS: A total of 108 people responded to the questionnaire. Sprains/strains and fractures accounted for 84.2% of respondents' injuries. Sixteen respondents (14.8%) required admission to hospital at the time of injury and 81 (75.0%) required subsequent healthcare appointments following discharge from the ED or hospital. Time off work or school following the injury was common (64.8% of respondents) and 27.8% of respondents had a carer take time off work. More than 80% of respondents missed training and matches following the injury. The median healthcare cost per respondent was AUD$753 and the median cost due to work absence was AUD$1393. One-quarter of respondents reported a full recovery. CONCLUSIONS: Injuries to female Australian footballers can produce substantial healthcare and societal costs, which has important implications for healthcare provision and prioritising and implementing injury prevention programmes and post-injury rehabilitation.

Feasibility, Acceptability, and Safety of Faecal Microbiota Transplantation in the Treatment of Major Depressive Disorder: A Pilot Randomized Controlled Trial.

OBJECTIVES: Perturbations of the intestinal microbiota have been associated with mental health disorders, including major depressive disorder (MDD). Therefore, faecal microbiota transplantation (FMT) holds promise as a microbiota-modulating treatment for MDD. Yet, to date, there are no published controlled studies evaluating the use of FMT for MDD. This study aimed to address this gap by evaluating the feasibility, acceptability, and safety of FMT for MDD. METHODS: The study was an 8-week, double-blind, 2:1 parallel group, randomized controlled pilot trial (n = 15) of enema-delivered FMT (n = 10) compared with a placebo enema (n = 5) in adults with moderate-to-severe MDD. RESULTS: Recruitment was completed within 2 months, with 0% attrition and 100% attendance at key study appointments. There were no major protocol deviations. The placebo and blinding strategies were considered successful; nurses and participants correctly guessing their treatment allocation at a rate similar to that anticipated by chance. No serious or severe adverse events were reported in either group, and there were no significant differences in mild-to-moderate adverse events between groups (median of 2 adverse events per participant reported in both groups). Furthermore, the 12/15 participants who completed the Week 2 participant satisfaction survey agreed or strongly agreed that the enema delivery was tolerable and that they would have the treatment again if required. Whilst the study was not designed to measure clinical outcomes, exploratory data also suggested that the active FMT treatment may lead to improvements in gastrointestinal symptoms and quality of life in this population, noting that irritable bowel syndrome is commonly comorbid with MDD. CONCLUSIONS: All feasibility targets were met or exceeded. This study found that enema-delivered FMT is feasible, acceptable, well-tolerated, and safe in patients with MDD. The findings of this study support further research to evaluate clinical efficacy, and the use of this protocol is supported.

Burden and preference-based quality of life associated with bullying in children.

The objectives of this study are to assess the association between childhood bullying and preference-based health-related quality of life (QoL) in Australian school children and their parents and estimate quality-adjusted life years (QALYs) associated with bullying chronicity. Children aged 8-10 years completed the child health utilities (CHU-9D), while parents completed the Australian quality of life (AQoL-8D). Children were grouped into four categories of bullying involvement (no bullying, victim, perpetrator, or both perpetrator and victim) based on the Revised Olweus Bully/Victim Questionnaire. Parental data were compared across two bullying involvement groups (bullying vs. no bullying). QALYs were calculated for children over two years and comparisons made based on the number of assessments where bullying was reported (baseline, 1- and 2-year follow up). Children who were involved in bullying (victims and/or perpetrators) reported statistically significantly lower mean utility scores compared to children who were not involved in bullying. Parents whose child was involved in bullying had significantly lower mean utility scores compared to parents of children not involved with bullying. There appeared to be a dose-response relationship, with higher QALY losses associated with increasing frequency of reported bullying. Bullying among Australian school children was associated with significantly lower preference-based QoL for themselves and their parents. This study also confirmed the significant burden of disease for bullying among children measured by an incremental decrease in QALY with an increasing chronicity of bullying over time.

Systematic review of the efficacy, effectiveness, and cost-effectiveness of stepped-care interventions for the prevention and treatment of problematic substance use.

BACKGROUND: Stepped-care is a commonly recommended and implemented care model across health care domains, including substance use. Despite their presumed efficient allocation of treatment resources, a current and robust evidence synthesis is needed on the efficacy, effectiveness and cost-effectiveness of stepped-care for substance use. METHODS: This systematic review analyzed articles describing evaluations of stepped-care models that measured the use of acutely psychoactive substances (i.e., alcohol, cannabis, hallucinogens, inhalants, opioids, sedatives, hypnotics, anxiolytics, and stimulants) as a primary or secondary outcome, in participants over 18 years old. The analysis investigated model and participant characteristics associated with treatment outcomes. RESULTS: The study team conducted a search of five databases of literature (PsychINFO, MEDLINE, Embase, Cochrane Library and Scopus) published between January 1, 2010, and November 1, 2020. The search yielded 1051 unique articles, 19 of which were included in the analysis. The studies had considerable variability in sample sizes (n = 18-2310), time to follow-up (4.5 months to 3 years), and retention rates (35.1-100 %). Studies examined outcomes for either alcohol alone (n = 9), alcohol and other drug use (n = 9), or drug use alone (n = 1). Most studies (n = 13;) were rated as good quality. Three (15.8 %) were rated as fair and three (15.8 %) were rated as poor quality. The evidence regarding the efficacy, effectiveness and cost-effectiveness of stepped-care approaches is limited, but four of seven studies found that adaptive-care interventions delivered in the context of other systemic interventions produced greater benefit than control conditions in relation to at least one alcohol-related outcome. We have insufficient evidence to determine whether the modes or intensity of interventions included in the models, or decision rules used to step people up or down to differing levels of care, have an impact on outcome. CONCLUSION: Heterogeneity between studies with regard to model and evaluation design limited the degree to which the analysis could draw robust conclusions. Sample recruitment and statistical power are particular challenges, and the field needs more innovative evaluation designs to assess the efficacy, effectiveness, and cost-effectiveness of stepped-care models.