Long-read sequencing of CYP2D6 may improve psychotropic prescribing and treatment outcomes: A systematic review and meta-analysis.

BACKGROUND: The enzyme expression (i.e. phenotype) of the Cytochrome P450 2D6 (CYP2D6) gene is highly relevant to the metabolism of psychotropic medications, and therefore to precision medicine (i.e. personalised prescribing). AIMS: This review aims to assess the improvement in CYP2D6 phenotyping sensitivity (IPS) and accuracy (IPA) offered by long-read sequencing (LRS), a new genetic testing technology. METHODS: Human DNA samples that underwent LRS genotyping of CYP2D6 in published, peer-reviewed clinical research were eligible for inclusion. A systematic literature search was conducted until 30 September 2023. CYP2D6 genotypes were translated into phenotypes using the international consensus method. IPS was the percentage of non-normal LRS CYP2D6 phenotypes undetectable with FDA-approved testing (AmpliChip). IPA was the percentage of LRS CYP2D6 phenotypes mischaracterised by non-LRS genetic tests (for samples with LRS and non-LRS data). RESULTS: Six studies and 1411 samples were included. In a meta-analysis of four studies, IPS was 10% overall (95% CI = (2, 18); n = 1385), 20% amongst Oceanians (95% CI = (17, 23); n = 582) and 2% amongst Europeans (95% CI = (1, 4); n = 803). IPA was 4% in a large European cohort (95% CI = (2, 7); n = 567). When LRS was used selectively (e.g. for novel or complex CYP2D6 genotypes), very high figures were observed for IPS (e.g. 88%; 95% CI = (72, 100); n = 17; country = Japan) and IPA (e.g. 76%; 95% CI = (55, 98); n = 17; country = Japan). CONCLUSIONS: LRS improves CYP2D6 phenotyping compared to established genetic tests, particularly amongst Oceanian and Japanese individuals, and those with novel or complex genotypes. LRS may therefore assist in optimising personalised prescribing of psychotropic medications. Further research is needed to determine associated clinical benefits, such as increased medication safety and efficacy.

Recurrent Mental Health Presentations to Public Hospital Services: A Focus on Borderline Personality Disorder.

Objective: To investigate associations between patients with borderline personality disorder (BPD)-related symptoms and their hospital presentations as well as the effect of inpatient length of stay (LOS) on time to hospital re-presentation.Methods: A retrospective cohort design was used to investigate mental health emergency department (ED) visits and inpatient admissions. The cohort comprised 13,320 men and 12,290 women with a follow-up period between January 1, 2014, and December 31, 2019.Results: Across all presentations in the study period, approximately 4% of mental health patients were discharged from ED or inpatient admission with primary diagnosis of BPD. Both male and female patients with BPD were at higher risk of hospital re-presentation when compared to patients with any other type of mental disorder (P < .01). Patients with BPD who had LOS > 14 days in their first inpatient admission were, on average, more likely to experience a repeat ED or inpatient presentation 58 days sooner than patients who had LOS < 2 days (P = .036).Conclusions: Findings suggest the need for (a) more accurate recording of BPD and related presentations, (b) more in-depth investigations of BPD care pathways, and (c) identifications of subpopulations who may benefit from a specific inpatient length of stay.Prim Care Companion CNS Disord 2024;26(1):23m03559. Author affiliations are listed at the end of this article.

Much Ado About Nothing? The Role of Land-Based Gambling Venue Employees in Facilitating Problem Gambling Harm Reduction and Help-Seeking.

Over the past decade, greater emphasis has been placed on the role of the land-based gambling industry to respond to problem gambling behaviour in their venues. Despite this, there is a lack of clear information advising best practice responses by gambling venue employees. This article reviews strategies, practices, and policies employed by land-based gambling venues concerning their employees' role in preventing gambling-related harm and responding to problem gambling behaviours. A systematic search strategy was applied to source peer-reviewed literature which identified 49 articles. The synthesised results were arranged and presented across five categories: (1) the identification of gamblers with potential problems in the venue; (2) gambling venue staff responses to gamblers with potential problems; (3) gamblers' perspectives around venue responsibilities and interactions with gamblers with potential problems; (4) corporate social responsibility programs and the identification of gamblers with problems in the venue; and (5) gambling venue staff needs. The results suggest that most activity performed by venue staff concerning their response to problem gambling is limited to observing and documenting risky behaviours and then discussing this internally with other venue staff. Action which moves beyond this, such as approaching and interacting with identified gamblers of concern, rarely occurs. The results of this review suggest that a focus on the identification and intervention specifically with identified gamblers of concern is a particularly unhelpful aspect of the role of venue staff. The results also indicate that a re-thinking of the role frontline staff play in addressing problem gambling is necessary.

Barriers and facilitators to the implementation of the Flinders Chronic Condition Management Program in outpatient drug and alcohol settings in Australia.

INTRODUCTION: There has been a growing call for drug and/or alcohol dependence to be managed as a chronic condition. The Flinders Chronic Condition Management Program (Flinders Program) was implemented in a drug and alcohol service in Australia in 2019-2022 to explore the feasibility of chronic condition management in outpatient clinics. Implementation involved: adaptation of the Flinders Program; adaptation of clinical procedures; training clinicians and managers; training Flinders Program Accredited Trainers; and system integration. This study aims to explore barriers and enablers to implementation. METHODS: A qualitative formative evaluation was undertaken. Data included implementation documents (n = 7), responses to open-ended questions in post-training surveys (n = 27), and focus groups and interviews with implementation staff, clinicians, managers and a trainer (n = 16). Data were analysed using the Consolidated Framework for Implementation Research in a 'coding reliability' approach to thematic analysis. RESULTS: Participants responded positively to the Flinders Program's philosophy, processes, tools and training. However, barriers were identified across three Consolidated Framework for Implementation Research domains: (i) outer setting (client suitability and incompatibility with external policies and incentives); (ii) characteristics of individuals (low self-efficacy); and (iii) inner setting (lack of system and workflow integration). DISCUSSION AND CONCLUSIONS: Executive support and systems integration are important for the implementation of the Flinders Program in drug and alcohol services. This needs to be achieved within externally mandated key performance indicators for outpatient services. Further research is needed to fully evaluate the potential of a chronic condition management framework in Australian outpatient drug and alcohol services.

Comparison of short and long forms of the Flinders program of chronic disease SELF-management for participants starting SGLT-2 inhibitors for congestive heart failure (SELFMAN-HF): protocol for a prospective, observational study.

Introduction: Congestive heart failure (CHF) causes significant morbidity and mortality. It is an epidemic, and costs are escalating. CHF is a chronic disease whose trajectory includes stable phases, periods of decompensation, and finally palliation. Health services and medical therapies must match the various patient needs. Chronic disease self-management (CDSM) programmes that are patient-focused, identify problems and set actionable goals that appear as a logical, cost-friendly method to navigate patient journeys. There have been challenges in standardising and implementing CHF programmes. Methods and analysis: SELFMAN-HF is a prospective, observational study to evaluate the feasibility and validity of the SCRinHF tool, a one-page self-management and readmission risk prediction tool for CHF, with an established, comprehensive CDSM tool. Eligible patients will have CHF with left ventricular ejection fraction <40% and commenced sodium glucose co-transporter-2 inhibitors (SGLT2-i) within 6 months of recruitment. The primary endpoint is the 80% concordance in readmission risk predicted by the SCRinHF tool. The study will recruit >40 patients and is expected to last 18 months. Ethics and dissemination: This study has been approved by the St Vincent's ethics committee (approval no. LRR 177/21). All participants will complete a written informed consent prior to enrolment in the study. The study results will be disseminated widely via local and international health conferences and peer-reviewed publications.

Gambling problems predict suicidality in recently transitioned military veterans.

OBJECTIVE: This study investigated associations between gambling problems and suicidality in Australian veterans. METHODS: Data drawn from n = 3,511 Australian Defence Force veterans who had recently transitioned to civilian life. Gambling problems were assessed using the Problem Gambling Severity Index (PGSI) and suicidal ideation and behaviour were assessed using items adapted from the National Survey of Mental Health and Wellbeing. RESULTS: At-risk gambling and problem gambling were associated with increased odds of suicidal ideation [at-risk gambling: odds ratio (OR), 1.93; 95% confidence interval (CI), 1.47‒2.53; problem gambling: OR, 2.75; 95% CI 1.86‒4.06] and suicide planning or attempts (at-risk gambling: OR, 2.07; 95% CI, 1.39‒3.06; problem gambling: OR 4.22, 95% CI, 2.61‒6.81). The association with total scores on the PGSI and any suicidality was substantially reduced and became non-significant when controlling for the effects of depressive symptoms, but not financial hardship or social support. CONCLUSIONS: Gambling problems and harms are important risk factors for suicide in veterans, and should be recognised in veteran-specific suicide prevention policies and programs, along with co-occurring mental health problems. IMPLICATIONS FOR PUBLIC HEALTH: A comprehensive public health approach to reducing gambling harm should feature in suicide prevention efforts in veteran and military populations.

Massed v. standard prolonged exposure therapy for PTSD in military personnel and veterans: 12-month follow-up of a non-inferiority randomised controlled trial.

BACKGROUND: The utilisation of massed therapy for treating posttraumatic stress disorder (PTSD) is gaining strength, especially prolonged exposure. However, it is unknown whether massed prolonged exposure (MPE) is non-inferior to standard prolonged exposure (SPE) protocols in the long term. The current study aimed to assess whether MPE was non-inferior to SPE at 12 months post-treatment, and to ascertain changes in secondary measure outcomes. METHODS: A multi-site non-inferiority randomised controlled trial (RCT) compared SPE with MPE in 12 clinics. The primary outcome was PTSD symptom severity (CAPS-5) at 12 months post-treatment commencement. Secondary outcome measures included symptoms of depression, anxiety, anger, disability, and quality of life at 12 weeks and 12 months post-treatment commencement. Outcome assessors were blinded to treatment allocation. The intention-to-treat sample included 138 Australian military members and veterans and data were analysed for 134 participants (SPE = 71, MPE = 63). RESULTS: Reductions in PTSD severity were maintained at 12 months and MPE remained non-inferior to SPE. Both treatment groups experienced a reduction in depression, anxiety, anger, and improvements in quality of life at 12 weeks and 12 months post-treatment commencement. Treatment effects for self-reported disability in the SPE group at 12 weeks were not maintained, with neither group registering significant effects at 12 months. CONCLUSIONS: The emergence of massed protocols for PTSD is an important advancement. The current study provides RCT evidence for the longevity of MPE treatment gains at 12 months post-treatment commencement and demonstrated non-inferiority to SPE. Promisingly, both treatments also significantly reduced the severity of comorbid symptoms commonly occurring alongside PTSD.

Comorbidities and their management in women with breast cancer-an Australian survey of breast cancer survivors.

PURPOSE: Breast cancer survivors experience significant burden from comorbid chronic conditions, but little is known about how well these conditions are managed. We conducted a national survey of Australian breast cancer survivors to examine the burden of chronic conditions, their impact and care alignment with the principles of chronic condition management. METHODS: A study-specific survey incorporated questions about chronic conditions using the Charlson Comorbidity Index (CCI), functional status using the Vulnerable Elders Survey (VES) and perceived quality of care for cancer and non-cancer conditions using the Patient Assessment of Care for Chronic Conditions Survey (PACIC). Members of Breast Cancer Network Australia (BCNA) were invited via email to complete the survey either online or through direct mail. RESULTS: The survey was sent to 2198 BCNA members and 177 responses were received (8.1%). Respondents were women aged 32-88 years (median 60.1 years). The majority were married (116; 67.7%) and had private insurance (137; 80.0%) and reported good to excellent health (119; 73.5%). Other health conditions were reported by 157 (88.7%), the most common being chronic pain (27.1%) and fatigue (22.0%). When asked about management of comorbidities or cancer, less than 20% were routinely asked about management goals, helped to set goals or asked about health habits. CONCLUSIONS: In this population of survivors with good health status and high rates of private insurance, comorbidities were common and their management, as well as management of breast cancer, was poorly aligned with chronic condition management principles.

Malthusian Trajectory for Heart Failure and Novel Translational Ambulatory Technologies.

INTRODUCTION: It has been estimated that congestive heart failure (CHF) will reach epidemic proportions and contribute to large unsustainable impacts on health budgets for any cardiovascular condition. Against other major trends in cardiovascular outcomes, readmission and disease burden continue to rise as the demographics shift. METHODS: The rise in heart failure with preserved ejection fraction (HFpEF) among elderly women will present new challenges. Gold standard care delivers sustainable and cost-effective health improvements using organised care programs. When coordinated with large hospitals, this can be replicated universally. RESULTS: A gradient of outcomes and ambulatory care needs to be shifted from established institutions and shared with clients and community health services, being a sizeable proportion of CHF care. CONCLUSION: In this review, we explore health technologies as an emerging opportunity to address gaps in CHF management.

The Australian version of IAPT: clinical outcomes of the multi-site cohort study of NewAccess.

BACKGROUND: The United Kingdom IAPT (Improving Access to Psychological Therapies) approach of delivering low intensity therapies for symptoms of depression and anxiety was adapted for Australia and named NewAccess. Clinical outcomes of the service were evaluated in three sites between October 2013 and 2016. AIMS: This paper describes the clinical outcomes in the Australian health setting. METHODS: Prospective cohort study with repeated measures. Both intent-to-treat and per protocol analyses were conducted for primary outcomes measures Patient Health Questionnaire-9 (nine item), and Generalised Anxiety Disorder (seven item). Secondary measures were Phobia Scale and Work and Social Adjustment Scale. RESULTS: Three thousand nine hundred and forty-six individuals were assessed, and 3269 attended at least two treatment sessions. Forty percent were males. There was a clinically meaningful reduction (improvement) shown by reliable recovery rates in both depression and anxiety symptoms at post-treatment assessment (68%; 95% CI: 66-70%) with large effect sizes (1.23 for depression and 1.25 for anxiety). Outcomes in PHQ-9 and GAD-7 were not influenced by age or sex, but recovery rates were significantly reduced by relationship status (single or separated). Unemployment reduced PHQ-9 outcomes but not GAD-7 outcomes. CONCLUSION: NewAccess demonstrated positive clinical outcomes in Australia, that compared favourably with international studies with the same methodology.

Effect of massed v. standard prolonged exposure therapy on PTSD in military personnel and veterans: a non-inferiority randomised controlled trial.

BACKGROUND: A short, effective therapy for posttraumatic stress disorder (PTSD) could decrease barriers to implementation and uptake, reduce dropout, and ameliorate distressing symptoms in military personnel and veterans. This non-inferiority RCT evaluated the efficacy of 2-week massed prolonged exposure (MPE) therapy compared to standard 10-week prolonged exposure (SPE), the current gold standard treatment, in reducing PTSD severity in both active serving and veterans in a real-world health service system. METHODS: This single-blinded multi-site non-inferiority RCT took place in 12 health clinics across Australia. The primary outcome was PTSD symptom severity measured by the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) at 12 weeks. 138 military personnel and veterans with PTSD were randomised. 71 participants were allocated to SPE, with 63 allocated to MPE. RESULTS: The intention-to-treat sample included 138 participants, data were analysed for 134 participants (88.1% male, M = 46 years). The difference between the mean MPE and SPE group PTSD scores from baseline to 12 weeks-post therapy was 0.94 [95% confidence interval (CI) -4.19 to +6.07]. The upper endpoint of the 95% CI was below +7, indicating MPE was non-inferior to SPE. Significant rates of loss of PTSD diagnosis were found for both groups (MPE 53.8%, SPE 54.1%). Dropout rates were 4.8% (MPE) and 16.9% (SPE). CONCLUSIONS: MPE was non-inferior to SPE in significantly reducing symptoms of PTSD. Significant reductions in symptom severity, low dropout rates, and loss of diagnosis indicate MPE is a feasible, accessible, and effective treatment. Findings demonstrate novel methods to deliver gold-standard treatments for PTSD should be routinely considered.

The Wider Considerations in Closing Chronic Disease Gaps - Focus on Heart Failure and Implementation.

BACKGROUND: Heart failure (HF) is predominately a chronic disease. There are overlaps in HF and chronic disease research and care. Chronic disease and HF research are conducted with multiple goals. The overarching goal is "optimized patient outcomes at maximum costeffectiveness". However, observations on patients can come with many variables; thus, we see differences in clinical translation. This document discusses an argument for three important gaps common to HF and chronic disease, i.e., screening, self-management, and patient-reported outcomes (PRO), and provides a glance of how it could fit into the evidence tree. Pertinent arguments for a framework for health services and models of care are provided as a prelude to future consensus. METHODOLOGY: 1) A preliminary literature review to identify a taxonomy for cardiovascular research, and 2) a review of the published literature describing the translation of research studies into clinical practice for cardiovascular disorders. A spectrum from observational to large randomized controlled trials to post-marketing studies were identified. DISCUSSION: A brief discussion on traditional research and differences focusing on screening, mixed methods research concepts, and chronic diseases models of care. Six steps to facilitate this: 1) Research design; 2) Research application (translation) i. routine ii. challenges; 3. Transforming research to translational level; 4. Funding and infrastructure; 5. Clinical Centres of Research Excellence (CCRE) and collaboration; 6. Governance and cost-effectiveness. CONCLUSION: Implementation research that aims to link research findings to improved patient outcomes in an efficient and effective way is a neglected area. Skills required to perform implementation research are complex. Ways to maximize translational impacts for chronic disease research to clinical practice are described in a HF context.

Managing electromyogram contamination in scalp recordings: An approach identifying reliable beta and gamma EEG features of psychoses or other disorders.

OBJECTIVE: In publications on the electroencephalographic (EEG) features of psychoses and other disorders, various methods are utilized to diminish electromyogram (EMG) contamination. The extent of residual EMG contamination using these methods has not been recognized. Here, we seek to emphasize the extent of residual EMG contamination of EEG. METHODS: We compared scalp electrical recordings after applying different EMG-pruning methods with recordings of EMG-free data from 6 fully paralyzed healthy subjects. We calculated the ratio of the power of pruned, normal scalp electrical recordings in the six subjects, to the power of unpruned recordings in the same subjects when paralyzed. We produced "contamination graphs" for different pruning methods. RESULTS: EMG contamination exceeds EEG signals progressively more as frequencies exceed 25 Hz and with distance from the vertex. In contrast, Laplacian signals are spared in central scalp areas, even to 100 Hz. CONCLUSION: Given probable EMG contamination of EEG in psychiatric and other studies, few findings on beta- or gamma-frequency power can be relied upon. Based on the effectiveness of current methods of EEG de-contamination, investigators should be able to reanalyze recorded data, reevaluate conclusions from high-frequency EEG data, and be aware of limitations of the methods.

The epigenetic reader PHF21B modulates murine social memory and synaptic plasticity-related genes.

Synaptic dysfunction is a manifestation of several neurobehavioral and neurological disorders. A major therapeutic challenge lies in uncovering the upstream regulatory factors controlling synaptic processes. Plant homeodomain (PHD) finger proteins are epigenetic readers whose dysfunctions are implicated in neurological disorders. However, the molecular mechanisms linking PHD protein deficits to disease remain unclear. Here, we generated a PHD finger protein 21B-depleted (Phf21b-depleted) mutant CRISPR mouse model (hereafter called Phf21bΔ4/Δ4) to examine Phf21b's roles in the brain. Phf21bΔ4/Δ4 animals exhibited impaired social memory. In addition, reduced expression of synaptic proteins and impaired long-term potentiation were observed in the Phf21bΔ4/Δ4 hippocampi. Transcriptome profiling revealed differential expression of genes involved in synaptic plasticity processes. Furthermore, we characterized a potentially novel interaction of PHF21B with histone H3 trimethylated lysine 36 (H3K36me3), a histone modification associated with transcriptional activation, and the transcriptional factor CREB. These results establish PHF21B as an important upstream regulator of synaptic plasticity-related genes and a candidate therapeutic target for neurobehavioral dysfunction in mice, with potential applications in human neurological and psychiatric disorders.

Prevalence of gambling problems, help-seeking, and relationships with trauma in veterans.

BACKGROUND AND AIMS: Veterans who have recently left the military (i.e., transitioned) may be vulnerable to the development of psychiatric disorders, but little is known about gambling problems in this population. This study investigated the prevalence and risk factors of gambling problems, help-seeking amongst veterans with gambling problems, and relationships with trauma and posttraumatic psychopathology. METHODS: Cross-sectional self-report survey data from 3,511 Australian Defence Force members who left the military within the past five years. Surveys included measures of gambling problems (PGSI); depressive symptoms (PHQ-9); posttraumatic stress disorder (PCL-5); help-seeking behaviours; military and non-military-related trauma. RESULTS: Prevalence rates for problem gambling (PGSI ≥ 5) were 4.6%, while an additional 8.8% were classified in terms of at-risk gambling (PGSI = 1-4). Time since leaving the military was not associated with gambling problems. Only 2.1% of veterans with problem gambling reported help-seeking for their gambling. While trauma exposure, depression, and Posttraumatic Stress Disorder (PTSD) were all related to gambling problems at the bivariate level, only arousal and dysphoric-related affect were uniquely associated with gambling problems when adjusting for covariates. DISCUSSION: Gambling problems may be under-recognised relative to other psychiatric issues. Posttraumatic mental health problems, rather than trauma exposure per se, may explain the relationship between trauma and gambling problems. CONCLUSIONS: Some veterans are in a period of vulnerability during transition out of military service, and harms associated with gambling problems may be exacerbated during this period.

An Audit of Mental Health Care Plans in Community Mental Health Services for Older Persons in Rural Communities in a State in Australia.

Mental health care planning is an important part of holistic, patient-centred care provision. Rural older adults represent a vulnerable population with unique and complex care needs requiring robust care planning approaches. This study's aim was to audit care plan documentation for rural older Australians against quality standards. A retrospective review of the care plans from electronic case records was performed for all patients who were 65 years or older and managed by rural community mental health teams over a 12-month period. 72.1% of patients had a care plan available. Multiple assessment areas were sparsely documented, such as cognition (32%), self-harm risk assessments (29.8%), visual impairment (5.5%), hearing issues (5%) and Advance Care Directives (35.4%). This study highlighted the need for the development and implementation of a care plan template specific to rural older patients. Further research into care planning processes and barriers to implementation is also required for this population.

Defining Vulnerable Patients with Heart Failure: Opportunistic Lessons from Covid-19.

Congestive Heart Failure is a chronic disease that can be associated with poor outcomes. Some patients are more vulnerable, while others who are vulnerable appear absent or silent to health services. COVID-19 pandemic is a good opportunity to explore this important area. This review focuses on chronic disease, heart failure and those who require greater consideration.

Perspective on 'Phase V' or Logistics and Regression as Logical Progression for Community Heart Failure Triage.

Congestive Heart Filur is an epidemic and its trajectory apppears to be escaling. Undoubtly tremendous gains have seen improvement in life expectancy and quality of life, however, hospital readmissions, resource utilization and health system cost continue to create challenges. In this short perspective, we raise the prospect of extending the research phases the community and real world setting. Logistic have supported service supply chains during the COVID-19 pandemic and there are lesson here to be learned.

Co-occurring depression and insomnia in Australian primary care: recent scientific evidence.

Depression and insomnia commonly co-occur, resulting in greater morbidity for patients, and difficult diagnostic and treatment decisions for clinicians. When patients report symptoms of both depression and insomnia, it is common for medical practitioners to conceptualise the insomnia as a secondary symptom of depression. This implies that there is little purpose in treating insomnia directly, and that management of depression will improve both the depression and insomnia symptoms. In this review, we present an overview of research investigating the comorbidity and treatment approaches for patients presenting with depression and insomnia in primary care. Evidence shows that clinicians should avoid routinely conceptualising insomnia as a secondary symptom of depression. This is because insomnia symptoms: (i) often occur before mood decline and are independently associated with increased risk of future depression; (ii) commonly remain unchanged following depression treatment; and (iii) predict relapse of depression after treatment for depression only. Furthermore, compared with control, cognitive behaviour therapy for insomnia improves symptoms of both depression and insomnia. It is critical that primary care clinicians dedicate specific diagnostic and treatment attention to the management of both depression (eg, psychotherapy, antidepressants) and insomnia (eg, cognitive behaviour therapy for insomnia administered by trained therapists or psychologists through a mental health treatment plan referral, by online programs, or by a general practitioner or nurse) when they co-occur. These treatments may be offered concurrently or sequentially (eg, insomnia treatment followed by depression treatment, or vice versa), depending on presenting symptoms, history, lifestyle factors and other comorbidities.

GamblingLess: A Randomised Trial Comparing Guided and Unguided Internet-Based Gambling Interventions.

There is little evidence relating to the effects of adding guidance to internet-based gambling interventions. The primary aim was to compare the effectiveness of an online self-directed cognitive-behavioural gambling program (GamblingLess) with and without therapist-delivered guidance. It was hypothesised that, compared to the unguided intervention, the guided intervention would result in superior improvements in gambling symptom severity, urges, frequency, expenditure, psychological distress, quality of life and help-seeking. A two-arm, parallel-group, randomised trial with pragmatic features and three post-baseline evaluations (8 weeks, 12 weeks, 24 months) was conducted with 206 gamblers (106 unguided; 101 guided). Participants in both conditions reported significant improvements in gambling symptom severity, urges, frequency, expenditure, and psychological distress across the evaluation period, even after using intention-to-treat analyses and controlling for other low- and high-intensity help-seeking, as well as clinically significant changes in gambling symptom severity (69% recovered/improved). The guided intervention resulted in additional improvements to urges and frequency, within-group change in quality of life, and somewhat higher rates of clinically significant change (77% cf. 61%). These findings, which support the delivery of this intervention, suggest that guidance may offer some advantages but further research is required to establish when and for whom human support adds value.