Trauma and comorbid post-traumatic stress disorder in people with bipolar disorder participating in the Heinz C. Prechter Longitudinal Study.

BACKGROUND: It is estimated that up to 50 % of people with bipolar disorder (BD) also have comorbid post-traumatic stress disorder (PTSD). However, little is known about the presentation and treatment of people with this comorbidity. METHODS: Data from 577 individuals diagnosed with bipolar disorder participating in the Heinz C. Prechter Longitudinal Study of BD were explored at baseline, year two and four. Three trauma groups were created: (i) one trauma (n = 75), (ii) multiple traumas (n = 417), and comorbid PTSD (n = 85). Measures of depression, mania, sleep, number of hospitalisations, suicide attempts, and medication use were analysed using regression modelling to determine differences between the three trauma groups. RESULTS: There was an increase in depression, mania, and sleep scores and a higher number of hospitalisations in participants with comorbid PTSD compared to those experiencing one trauma. Additionally, increased mania and depression scores were reported in participants experiencing multiple traumas compared to those with one trauma. There was no difference in medication use between those who experienced one trauma compared to those with comorbid PTSD. LIMITATIONS: The trauma groups may include confounding with more participants experiencing PTSD than reported in this study due to screening processes. Additionally, the severity of trauma was not recorded, therefore number of traumas was utilised as a proxy. CONCLUSION: Comorbid BD and PTSD is associated with worse symptom scores compared to participants reporting one trauma. Clinical implications include the addition of trauma-informed care to clinical settings to identify PTSD to provide appropriate treatments.

Health risk factors in Australian Stroke Survivors: A latent class analysis.

ISSUES ADDRESSED: To (i) determine the prevalence of health risk factors (physical activity, diet, alcohol, smoking, blood pressure medication use and mental health) in community-dwelling stroke survivors; and (ii) examine how these health risk factors cluster, and identify associations with physical functioning, independent living, or sociodemographic factors. METHODS: A secondary analysis of data obtained during a national randomised controlled trial. Participants had experienced stroke and completed a baseline telephone survey on demographic and stroke characteristics, health risk factors, physical functioning and independence in activities of daily living. A latent class analysis was performed to determine health risk profiles. Univariate logistic regressions were performed to identify if participant characteristics were associated with resulting classes. RESULTS: Data analysed from 399 participants. Two classes of health risk factors were identified: Low Mood, Food & Moves Risk (16% of participants) and Alcohol Use Risk (84% of participants). The Low Mood, Food & Moves Risk group had poorer diet quality, lower physical activity levels and higher levels of depression and anxiety. Lower levels of independence and physical functioning were predictor variables for this group. In contrast, the Alcohol Use Risk group had better physical activity and diet scores, significantly lower probability of depression and anxiety, but a higher probability of risky drinking. CONCLUSIONS: We identified two distinct health risk factor groups in our population. SO WHAT?: Future interventions may benefit from targeting the specific needs and requirements of people who have experienced stroke based on their distinct risk group. Alcohol consumption in poststroke populations requires further attention.

'Quitlink': Outcomes of a randomised controlled trial of peer researcher facilitated referral to a tailored quitline tobacco treatment for people receiving mental health services.

OBJECTIVE: The aim of this study was to test the effectiveness of a tailored quitline tobacco treatment ('Quitlink') among people receiving support for mental health conditions. METHODS: We employed a prospective, cluster-randomised, open, blinded endpoint design to compare a control condition to our 'Quitlink' intervention. Both conditions received a brief intervention delivered by a peer researcher. Control participants received no further intervention. Quitlink participants were referred to a tailored 8-week quitline intervention delivered by dedicated Quitline counsellors plus combination nicotine replacement therapy. The primary outcome was self-reported 6 months continuous abstinence from end of treatment (8 months from baseline). Secondary outcomes included additional smoking outcomes, mental health symptoms, substance use and quality of life. A within-trial economic evaluation was conducted. RESULTS: In total, 110 participants were recruited over 26 months and 91 had confirmed outcomes at 8 months post baseline. There was a difference in self-reported prolonged abstinence at 8-month follow-up between Quitlink (16%, n = 6) and control (2%, n = 1) conditions, which was not statistically significant (OR = 8.33 [0.52, 132.09] p = 0.131 available case). There was a significant difference in favour of the Quitlink condition on 7-day point prevalence at 2 months (OR = 8.06 [1.27, 51.00] p = 0.027 available case). Quitlink costs AU$9231 per additional quit achieved. CONCLUSION: The Quitlink intervention did not result in significantly higher rates of prolonged abstinence at 8 months post baseline. However, engagement rates and satisfaction with the 'Quitlink' intervention were high. While underpowered, the Quitlink intervention shows promise. A powered trial to determine its effectiveness for improving long-term cessation is warranted.

The Influence of Personality Disorder Symptoms on Treatment Outcomes in Bipolar Disorder: A Secondary Analysis of a Randomised Controlled Trial: L'influence des symptômes du trouble de la personnalité sur les résultats du traitement dans le trouble bipolaire : Une analyse secondaire d'un essai randomisé contrôlé.

OBJECTIVES: Many people who are diagnosed with bipolar disorder also have comorbid personality disorder. Few studies have explored how personality disorder may influence pharmacological treatment outcomes. The aim of this study was to conduct a secondary analysis of data from a clinical trial of adjunctive nutraceutical treatments for bipolar depression, to determine whether maladaptive personality traits influence treatment outcomes. METHODS: Scores on the Standardised Assessment of Personality - Abbreviated Scale screener were used to classify participants as having bipolar disorder with (n = 119) and without (n = 29) above threshold personality disorder symptoms (personality disorder). Outcome measures included: The Montgomery Åsberg Depression Rating Scale, Clinical Global Impressions and Improvement Severity Scales, Patient Global Impressions-Improvement scale, Bipolar Depression Rating Scale, Range of Impaired Functioning Tool, Social and Occupational Functioning Assessment Scale and Quality of Life and Enjoyment Scale (Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form). Generalised estimated equations examined the two-way interactions of personality disorder by time or treatment and investigated personality disorder as a non-specified predictor of outcomes. RESULTS: Over time, the Patient Global Impressions-Improvement scores were significantly higher in those in the personality disorder group. No other significant differences in the two-way interactions of personality disorder by treatment group or personality disorder by time were found. Personality disorder was a significant but non-specific predictor of poorer outcomes on the Bipolar Depression Rating Scale, Range of Impaired Functioning Tool, and Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form, regardless of time or treatment group. CONCLUSIONS: This study highlights the potential impact of maladaptive personality traits on treatment outcomes and suggests that the presence of comorbid personality disorder may confer additional burden and compromise treatment outcomes. This warrants further investigation as does the corroboration of these exploratory findings. This is important because understanding the impact of comorbid personality disorder on bipolar disorder may enable the development of effective psychological and pharmacotherapeutic options for personalised treatments.

Surf therapy for improving child and adolescent mental health: A pilot randomised control trial.

The aim of this pilot randomised control trial (RCT) was to test, 1) feasibility and acceptability of a surf therapy program to improve symptoms of mental ill-health among children and adolescents, and 2) the design and procedures of an evaluative study. This pilot RCT compared a 6-week mentor-supported surf therapy program with a wait list control group, in Australian children and adolescents aged 8-18yrs (M age = 11.28, SD = 2.34; 15 females), who were help seeking for issues relating to their mental health. Exclusion criteria included if an individual was actively suicidal or experiencing a psychotic episode or being unavailable for program dates. The primary outcome was the feasibility and acceptability of the intervention and study design assessed via 11 pre-defined criteria. A secondary outcome was to investigate the effectiveness signal of the intervention on child indicators of depression and anxiety, assessed via the Revised Children's Anxiety and Depression Scale-Short Form and the Strengths and Difficulties Questionnaire. Random allocation was computer generated and while it was not possible to blind participants, researchers collecting assessments were blinded to group allocation. Thirty-six youth were randomised (intervention = 18; wait list controls = 18), representing an 84% participation rate among eligible youth. Of the 11 a priori feasibility and acceptability criteria, 4 of 5 relating to the intervention, and 4 of 6 addressing the study design were fully met, with the unmet factors guiding program revision. At the completion of the intervention, children and adolescents receiving the intervention reported reductions in symptoms of depression (ES = 0.57), anxiety (ES = 0.43), emotional problems, (ES = 0.79), peer problems (ES = 0.56), hyperactivity/inattention (ES = 0.28), and overall difficulties (ES = 0.64). These reductions were not sustained 6-weeks after completion of the intervention. Surf therapy is an acceptable and feasible intervention for addressing symptoms of mental ill-health among children and adolescents. Preliminary evidence suggests that surf therapy improves symptoms of mental ill-health in the short-term but that these improvements were not sustained after the intervention is ceased.

Does Post-traumatic Stress Disorder Impact Treatment Outcomes within a Randomised Controlled Trial of Mitochondrial Agents for Bipolar Depression?

Objective: Bipolar disorder often co-occurs with post-traumatic stress disorder, yet few studies have investigated the impact of post-traumatic stress disorder in bipolar disorder on treatment outcomes. The aim of this sub-analysis was to explore symptoms and functioning outcomes between those with bipolar disorder alone and those with comorbid bipolar disorder and post-traumatic stress disorder. Methods: Participants (n = 148) with bipolar depression were randomised to: (i) N-acetylcysteine alone; (ii) a combination of nutraceuticals; (iii) or placebo (in addition to treatment as usual) for 16 weeks (＋4 weeks discontinuation). Differences between bipolar disorder and comorbid bipolar disorder and post-traumatic stress disorder on symptoms and functioning at five timepoints, as well as on the rate of change from baseline to week 16 and baseline to week 20, were examined. Results: There were no baseline differences between bipolar disorder alone and comorbid bipolar disorder and post-traumatic stress disorder apart from the bipolar disorder alone group being significantly more likely to be married (p = 0.01). There were also no significant differences between bipolar disorder alone and comorbid bipolar disorder and post-traumatic stress disorder on symptoms and functioning. Conclusion: There were no differences in clinical outcomes over time within the context of an adjunctive randomised controlled trial between those with bipolar disorder alone compared to those with comorbid bipolar disorder and post-traumatic stress disorder. However, differences in psychosocial factors may provide targets for areas of specific support for people with comorbid bipolar disorder and post-traumatic stress disorder.

Metabolic regulation to treat bipolar depression: mechanisms and targeting by trimetazidine.

Bipolar disorder's core feature is the pathological disturbances in mood, often accompanied by disrupted thinking and behavior. Its complex and heterogeneous etiology implies that a range of inherited and environmental factors are involved. This heterogeneity and poorly understood neurobiology pose significant challenges to existing drug development paradigms, resulting in scarce treatment options, especially for bipolar depression. Therefore, novel approaches are needed to discover new treatment options. In this review, we first highlight the main molecular mechanisms known to be associated with bipolar depression-mitochondrial dysfunction, inflammation and oxidative stress. We then examine the available literature for the effects of trimetazidine in said alterations. Trimetazidine was identified without a priori hypothesis using a gene-expression signature for the effects of a combination of drugs used to treat bipolar disorder and screening a library of off-patent drugs in cultured human neuronal-like cells. Trimetazidine is used to treat angina pectoris for its cytoprotective and metabolic effects (improved glucose utilization for energy production). The preclinical and clinical literature strongly support trimetazidine's potential to treat bipolar depression, having anti-inflammatory and antioxidant properties while normalizing mitochondrial function only when it is compromised. Further, trimetazidine's demonstrated safety and tolerability provide a strong rationale for clinical trials to test its efficacy to treat bipolar depression that could fast-track its repurposing to address such an unmet need as bipolar depression.

How does a family history of psychosis influence the risk of methamphetamine-related psychotic symptoms: Evidence from longitudinal panel data.

AIMS: To determine whether the risk of psychotic symptoms during weeks of methamphetamine use was dependent on, increased by, or independent of having a family history of psychosis. DESIGN: Secondary analysis of 13 contiguous 1-week periods of data (1370 weeks). A risk modification framework was used to test each scenario. SETTING: Geelong, Wollongong and Melbourne, Australia. PARTICIPANTS: Participants in a randomized controlled trial of treatment for methamphetamine dependence (n = 148) who did not have a primary psychotic disorder on enrolment. MEASUREMENTS: Psychotic symptoms in the previous week were defined as a score of 3+ on any of the Brief Psychiatric Rating Scale items of hallucinations, unusual thought content or suspiciousness. Any (vs no) methamphetamine use in the previous week was assessed using the Timeline Followback method. Self-reported family history of psychosis was assessed using the Diagnostic Interview for Psychosis. FINDINGS: The risk of psychotic symptoms in the past week was independently associated with methamphetamine use in that week (relative risk [RR] = 2.3, 95% CI = 1.3-4.3) and with having a family history of psychosis (RR = 2.4, 95% CI = 0.9-7.0); the joint risk among participants with a family history of psychosis during weeks when they were using methamphetamine was large (RR = 4.0, 95% CI = 2.0-7.9). There was no significant interaction between a family history of psychosis and methamphetamine use in predicting psychotic symptoms (interaction RR = 0.7 95% CI = 0.3-1.8), but there was a small non-significant excess risk due to the interaction (0.20 95% CI = -1.63 to 2.03). CONCLUSIONS: Among people dependent on methamphetamine, the relative risk of psychotic symptoms during weeks of methamphetamine use does not appear to be dependent on, or increased by, having a family history of psychosis. However, a family history of psychosis does appear to be an independent risk factor that contributes to the absolute risk of psychotic symptoms in this population.

The Impact of N-acetylcysteine on Major Depression: Qualitative Observation and Mixed Methods Analysis of Participant Change during a 12-week Randomised Controlled Trial.

Objective: N-acetylcysteine (NAC) is a novel therapeutic agent with multiple mechanisms of action in the central nervous system and a favourable side effect profile. Clinical evidence indicates that adjunctive NAC may reduce the severity of depressive symptoms in individuals with major depressive disorder (MDD). Methods: A 12-week randomised controlled trial of 2,000 mg/day adjunctive NAC for MDD found no significant improvement at the primary endpoint (week 12) but did see improvements at the post-discontinuation interview (week 16). Within the context of patient-centered treatment, mixed-methods qualitative analysis was also included to explore factors that may determine individual responses to adjunctive NAC treatment. These data were drawn, under blinded conditions, from clinician notes recorded in the case report form. Using the DSM-5 symptom profile for MDD as the initial framework, themes were developed and explored. Frequencies were compared between placebo and NAC groups. Results: Per protocol analysis of individual themes across the six interviews revealed group differences in favour of NAC for overall depressive affect, optimism, relationships and reduced functional impairment. Conclusion: This study provides further evidence for the utility of the mixed methods approach complimenting the primary findings using traditional quantitative analyses, as well as being able to capture additional, often more subtle, evidence of individual symptom-level change that reflects improvement in functional abilities in response to NAC supplementation. The use of mixed methods to explore outcomes from psychiatric studies should be considered in future to work towards improved patient-centred care and both confirm quantitative findings and generate novel hypotheses.

Interpersonal Trauma and Depression Severity Among Individuals With Bipolar Disorder: Findings From the Prechter Longitudinal Study of Bipolar Disorder.

Background: Experiences of interpersonal trauma, both in childhood and in adulthood, can affect the trajectory of bipolar disorder (BD). However, the degree to which childhood and/or adult trauma impacts the longitudinal trajectory of depression severity among individuals with BD actively receiving treatment remains unclear.Methods: The effects of childhood trauma (Childhood Trauma Questionnaire) and adult trauma (Life Events Checklist) on depression severity (Hamilton Depression Rating Scale) were investigated in a treatment-receiving subsample with BD (DSM-IV) of the Prechter Longitudinal Study of Bipolar Disorder (2005-present). A mixed-effects linear regression model was used to assess the trajectory of depression severity over 4 years.Results: Depression severity was evaluated in 360 participants, of whom 267 (74.8%) reported a history of interpersonal trauma. A history of childhood trauma alone (n = 110) and childhood and adult trauma combined (n = 108)-but not adult trauma alone (n = 49) -were associated with greater depression severity at the 2-year and 6-year follow-up assessments. However, the trajectory of depression severity (ie, change over time) was similar between participants with a history of childhood trauma, those with a history of adult trauma, and those with no history of interpersonal trauma. Interestingly, participants with a history of both types of trauma showed more improvement in depression severity (ie, from year 2 to year 4: ß = 1.67, P = .019).Conclusions: Despite actively receiving treatment for BD, participants with a history of interpersonal trauma-particularly childhood trauma-presented with more severe depressive symptoms at several follow-up assessments. Hence, interpersonal trauma may represent an essential treatment target.

Minocycline as Treatment for Psychiatric and Neurological Conditions: A Systematic Review and Meta-Analysis.

Minocycline has anti-inflammatory, antioxidant, and anti-apoptotic properties that explain the renewed interest in its use as an adjunctive treatment for psychiatric and neurological conditions. Following the completion of several new clinical trials using minocycline, we proposed an up-to-date systematic review and meta-analysis of the data available. The PICO (patient/population, intervention, comparison and outcomes) framework was used to search 5 databases aiming to identify randomized controlled trials that used minocycline as an adjunctive treatment for psychiatric and neurological conditions. Search results, data extraction, and risk of bias were performed by two independent authors for each publication. Quantitative meta-analysis was performed using RevMan software. Literature search and review resulted in 32 studies being included in this review: 10 in schizophrenia, 3 studies in depression, and 7 in stroke, with the benefit of minocycline being used in some of the core symptoms evaluated; 2 in bipolar disorder and 2 in substance use, without demonstrating a benefit for using minocycline; 1 in obsessive-compulsive disorder, 2 in brain and spinal injuries, 2 in amyotrophic lateral sclerosis, 1 in Alzheimer's disease, 1 in multiple systems atrophy, and 1 in pain, with mixes results. For most of the conditions included in this review the data is still limited and difficult to interpret, warranting more well-designed and powered studies. On the other hand, the studies available for schizophrenia seem to suggest an overall benefit favoring the use of minocycline as an adjunctive treatment.

Childhood trauma and depressive symptoms in bipolar disorder: A network analysis.

BACKGROUND: Childhood trauma is related to an increased number of depressive episodes and more severe depressive symptoms in bipolar disorder. The evaluation of the networks of depressive symptoms-or the patterns of relationships between individual symptoms-among people with bipolar disorder with and without a history of childhood trauma may assist in further clarifying this complex relationship. METHODS: Data from over 500 participants from the Heinz C. Prechter Longitudinal Study of Bipolar Disorder were used to construct a series of regularised Gaussian Graphical Models. The networks of individual depressive symptoms-self-reported (Patient Health Questionnaire-9; n = 543) and clinician-rated (Hamilton Depression Rating Scale-17; n = 529)-among participants with bipolar disorder with and without a history of childhood trauma (Childhood Trauma Questionnaire) were characterised and compared. RESULTS: Across the sets of networks, depressed mood consistently emerged as a central symptom (as indicated by strength centrality and expected influence); regardless of participants' history of childhood trauma. Additionally, feelings of worthlessness emerged as a key symptom in the network of self-reported depressive symptoms among participants with-but not without-a history of childhood trauma. CONCLUSION: The present analyses-although exploratory-provide nuanced insights into the impact of childhood trauma on the presentation of depressive symptoms in bipolar disorder, which have the potential to aid detection and inform targeted intervention development.

Personality traits as mediators of the relationship between childhood trauma and depression severity in bipolar disorder: A structural equation model.

BACKGROUND: Childhood trauma is negatively associated with depression severity in bipolar disorder; however, the underlying mechanisms remain unclear. We investigated whether personality traits (neuroticism, extraversion, openness, agreeableness, conscientiousness) mediate the relationship between childhood trauma and the severity of bipolar depression. METHODS: Data from 209 individuals with bipolar disorder recruited for the Prechter Longitudinal Study of Bipolar Disorder were analysed. Using structural equation modelling, we examined the direct and indirect associations between childhood trauma (Childhood Trauma Questionnaire) and depression severity (Hamilton Depression Rating Scale) - with the personality traits (NEO Personality Inventory-Revised) as mediators. RESULTS: The direct effect of childhood trauma on depression severity (standardised ß = 0.32, 95% bootstrap confidence interval [CI] = 0.20-0.45, p < 0.001) and the indirect effect via neuroticism (standardised ß = 0.03, 95% bootstrap CI [0.002, 0.07], p = 0.039) were significant; supporting a partial mediation model. The indirect effect accounted for 9% of the total effect of childhood trauma on depression severity (standardised ß = 0.09, 95% bootstrap CI [0.002, 0.19], p = 0.046). The final model had a good fit with the data (comparative fit index = 0.96; root mean square error of approximation = 0.05, 90% CI = [0.02, 0.07]). CONCLUSION: Personality traits may be relevant psychological mediators that link childhood trauma to a more severe clinical presentation of bipolar depression. Consequently, a person's personality structure may be a crucial operative factor to incorporate in therapeutic plans when treating individuals with bipolar disorder who report a history of childhood trauma.

Diagnostic accuracy for self-reported methamphetamine use versus oral fluid test as the reference standard in a methamphetamine-dependent intervention trial population.

AIMS: Treatment of methamphetamine dependence requires monitoring of recent use or abstinence. Self-report is commonly used for routine monitoring, but the accuracy of self-report is not established. For the treating clinician, the key accuracy statistic is the negative predictive value (NPV). The study aim was to estimate the NPV of self-reported non-use of methamphetamine compared with an oral fluid reference standard. DESIGN, SETTING AND PARTICIPANTS: This study was a secondary (subgroup) analysis from a randomized controlled pharmacotherapy trial. Three Australian outpatient addiction services took part. Particpants were 139 people dependent on methamphetamine. MEASUREMENTS: Weekly oral fluid samples over 12 weeks to determine methamphetamine (and amphetamine) concentrations were used as the reference standard. Self-report of any methamphetamine use in the previous 7 days by the time-line follow-back method was the index test. Standard diagnostic accuracy statistics were calculated for all available paired episodes (n = 1134). Three NPV values were calculated: unadjusted NPV and NPV adjusted for clustering of observations through logistic regression and generalized estimating equation (GEE). We also calculated the NPVs for a range of prevalence rates of methamphetamine use, for the calculated levels of sensitivity and specificity. FINDINGS: Sensitivity was 96.4% [95% confidence interval (CI) = 95-97.5], specificity was 63.7% (95% CI = 57.3-69.8) and positive predictive value (PPV) was 90.8% (95% CI = 88.8-92.6). The unadjusted NPV was 82.7% (95% CI = 76.5-87.9), adjusted NPV by logistic regression 82.7% (95% CI = 73.9-91.5) and GEE 76.8% (95% CI = 66.8-86.8). At a methamphetamine use prevalence of 5%, the estimated NPV would be 99.7% (95% CI = 99.6-99.9) and at 95% prevalence, 48.2% (95% CI = 39.6-57.0). CONCLUSIONS: Self-report of no recent methamphetamine use appears to be sufficiently accurate to be clinically useful at the expected prevalence rates of methamphetamine use in clinical treatment settings. If generalizable to clinical settings, where these tests are routinely conducted, this may permit a reduction in the frequency and cost of oral fluid assays.

The Impact of Posttraumatic Stress Disorder on Pharmacologic Intervention Outcomes for Adults With Bipolar Disorder: A Systematic Review.

BACKGROUND: The prevalence of posttraumatic stress disorder (PTSD) co-occurring in people with bipolar disorder (BD) is high. People with BD and PTSD may experience different outcomes and quality of life after pharmacologic treatment than those with BD alone. This review systematically explores the impact of PTSD on pharmacologic treatment outcomes for adults with BD. METHODS: We conducted a systematic search up to November 25, 2021, using MEDLINE Complete, Embase, American Psychological Association PsycInfo, and the Cochrane Central Register of Controlled Trials to identify randomized and nonrandomized studies of pharmacologic interventions for adults with BD that assessed for comorbid PTSD. We used the Newcastle-Ottawa Scale and Cochrane Risk of Bias tool to assess the risk of bias. RESULTS: The search identified 5093 articles, and we reviewed 62 full-text articles. Two articles met inclusion criteria (N = 438). One article was an observational study, and the other was a randomized comparative effectiveness trial. The observational study examined lithium response rates and found higher response rates in BD alone compared with BD plus PTSD over 4 years. The randomized trial reported more severe symptoms in the BD plus PTSD group than in those with BD alone following 6 months of quetiapine treatment. There was no significant difference in the lithium treatment group at follow-up. CONCLUSIONS: Comorbid PTSD may affect quetiapine and lithium treatment response in those with BD. Because of the high risk of bias and low quality of evidence, however, these results are preliminary. Specific studies exploring comorbid BD and PTSD are required to inform pharmacotherapy selection and guidelines appropriately. (International Prospective Register of Systematic Reviews ID: CRD42020182540).

The value of compassionate support to address smoking: A qualitative study with people who experience severe mental illness.

Introduction: People experiencing severe mental illness (SMI) smoke at much higher rates than the general population and require additional support. Engagement with existing evidence-based interventions such as quitlines and nicotine replacement therapy (NRT) may be improved by mental health peer worker involvement and tailored support. This paper reports on a qualitative study nested within a peer researcher-facilitated tobacco treatment trial that included brief advice plus, for those in the intervention group, tailored quitline callback counseling and combination NRT. It contextualizes participant life experience and reflection on trial participation and offers insights for future interventions. Methods: Qualitative semi-structured interviews were conducted with 29 participants in a randomized controlled trial (intervention group n = 15, control group n = 14) following their 2-month (post-recruitment) follow-up assessments, which marked the end of the "Quitlink" intervention for those in the intervention group. Interviews explored the experience of getting help to address smoking (before and during the trial), perceptions of main trial components including assistance from peer researchers and tailored quitline counseling, the role of NRT, and other support received. A general inductive approach to analysis was applied. Results: We identified four main themes: (1) the long and complex journey of quitting smoking in the context of disrupted lives; (2) factors affecting quitting (desire to quit, psychological and social barriers, and facilitators and reasons for quitting); (3) the perceived benefits of a tailored approach for people with mental ill-health including the invitation to quit and practical resources; and (4) the importance of compassionate delivery of support, beginning with the peer researchers and extended by quitline counselors for intervention participants. Subthemes were identified within each of these overarching main themes. Discussion: The findings underscore the enormity of the challenges that our targeted population face and the considerations needed for providing tobacco treatment to people who experience SMI. The data suggest that a tailored tobacco treatment intervention has the potential to assist people on a journey to quitting, and that compassionate support encapsulating a recovery-oriented approach is highly valued. Clinical trial registration: The Quitlink trial was registered with ANZCTR (www.anzctr.org.au): ACTRN12619000244101 prior to the accrual of the first participant and updated regularly as per registry guidelines.

Adapting Peer Researcher Facilitated Strategies to Recruit People Receiving Mental Health Services to a Tobacco Treatment Trial.

Introduction: One of the most challenging aspects of conducting intervention trials among people who experience severe mental illness (SMI) and who smoke tobacco, is recruitment. In our parent "QuitLink" randomized controlled trial (RCT), slower than expected peer researcher facilitated recruitment, along with the impact of COVID-19 pandemic restrictions, necessitated an adaptive recruitment response. The objectives of the present study were to: (i) describe adaptive peer researcher facilitated recruitment strategies; (ii) explore the effectiveness of these strategies; (iii) investigate whether recruitment strategies reached different subgroups of participants; and (iv) examine the costs and resources required for implementing these strategies. Finally, we offer experience-based lessons in a Peer Researcher Commentary. Methods: People were included in the RCT if they smoked at least 10 cigarettes a day and were accessing mental health support from the project's two partnering mental health organizations in Victoria, Australia. The majority of people accessing these services will have been diagnosed with SMI. Recruitment occurred over 2 years. We began with peer facilitated recruitment strategies delivered face-to-face, then replaced this with direct mail postcards followed by telephone contact. In the final 4 months of the study, we began online recruitment, broadening it to people who smoked and were accessing support or treatment (including from general practitioners) for mental health and/or alcohol or other drug problems, anywhere in the state of Victoria. Differences between recruitment strategies on key participant variables were assessed. We calculated the average cost per enrolee of the different recruitment approaches. Results: Only 109 people were recruited from a target of 382: 29 via face-to-face (March 2019 to April 2020), 66 from postcards (May 2020 to November 2020), and 14 from online (November to December 2020 and January to March 2021) strategies. Reflecting our initial focus on recruiting from supported independent living accommodation facilities, participants recruited face-to-face were significantly more likely to be living in partially or fully supported independent living (n = 29, <0.001), but the samples were otherwise similar. After the initial investment in training and equipping peer researchers, the average cost of recruitment was AU$1,182 per participant-~US$850. Face-to-face recruitment was the most expensive approach and postcard recruitment the least (AU$1,648 and AU$928 per participant). Discussion: Peer researcher facilitated recruitment into a tobacco treatment trial was difficult and expensive. Widely dispersed services and COVID-19 restrictions necessitated non-face-to-face recruitment strategies, such as direct mail postcards, which improved recruitment and may be worthy of further research. Clinical Trial Registration: The trial is registered with ANZCTR (www.anzctr.org.au): ACTRN12619000244101 prior to the accrual of the first participant and updated regularly as per registry guidelines. The trial sponsor was the University of Newcastle, NSW, Australia.

Access to and Use of Internet and Social Media by Low-Morbidity Stroke Survivors Participating in a National Web-Based Secondary Stroke Prevention Trial: Cross-sectional Survey.

BACKGROUND: eHealth applications for stroke are a growing area of research that has yielded promising results. However, little is known about how stroke survivors engage with the internet, social media, and other digital technologies on a day-to-day basis. OBJECTIVE: This study had three main objectives: to describe the type, frequency, and purpose of technology use among a cohort of low-morbidity stroke survivors; to investigate associations between social media use and participant factors, including sociodemographics, physical function, and independence in activities of daily living; and to investigate associations between stroke-related health risk factors and the use of the internet to search for health and medical information. METHODS: This study is a secondary analysis of data obtained during a national randomized controlled trial-Prevent 2nd Stroke. The participants were stroke survivors recruited from 2 Australian stroke registries who completed 2 telephone-administered surveys to collect data on demographics and stroke characteristics; health risk factors (diet quality, physical activity, blood pressure medication, alcohol intake, anxiety and depression, and smoking status); physical functioning; independence in activities of daily living; and questions about what technology they had access to, how often they used it, and for what purposes. Participants were eligible if they had no more than a moderate level of disability (modified Rankin score ≤3) and had access to the internet. Multivariable logistic regression was used to assess the associations between social media use and sociodemographics, physical function, and independence in activities of daily living as well as associations between stroke-related health risk factors and the use of the internet to search for health and medical information. RESULTS: Data from 354 participants were included in the analysis. Approximately 79.1% (280/354) of participants used the internet at least daily, 40.8% (118/289) accessed social media on their phone or tablet daily, and 46.4% (134/289) looked up health and medical information at least monthly. Women were 2.7 times more likely to use social media (adjusted odds ratio 2.65, 95% CI 1.51-4.72), and people aged >75 years were significantly less likely to use social media compared with those aged <55 years (adjusted odds ratio 0.17, 95% CI 0.07-0.44). Health risk factors were not found to be associated with searching for health- or medical-related information. CONCLUSIONS: The internet appears to be a viable platform to engage with stroke survivors who may not be high-morbidity to conduct research and provide information and health interventions. This is important given that they are at high risk of recurrent stroke regardless of their level of disability. Exploring the technology use behaviors and the possibility of eHealth among survivors who experience higher levels of morbidity or disability because of their stroke is an area of research that warrants further study.

Mixed Methods Thematic Analysis of a Randomised Controlled Trial of Adjunctive Mitochondrial Agents for Bipolar Depression.

Objective: There is often a shortfall in recovery following treatment for an episode of bipolar disorder (BD). Exploration of participant's experience provides vital information to enhance statistical outcomes for novel therapy trials. This study used mixed-methods to explore participants' experience of a trial testing N -acetyl cysteine (NAC) and mitochondrially active nutraceuticals for BD depression. Case: report forms from a randomised controlled trial (RCT) of BD depression (n = 148) were analysed using a pragmatic adaption of grounded theory and thematic analysis. Results: Thematic analysis of 148 study participants indicated numerous changes in participant experience over time. For example, perceived environmental stressors reported by participants decreased over the trial in both treatment groups. Quantitative analysis of the themes revealed more positive theme reports in the combination treatment arm compared to the placebo arm and there were more negative themes identified in the placebo arm, compared to the NAC arm. Conclusion: This approach revealed additional results not elucidated in the primary quantitative analysis. This emphasises the value of mixed-methods research in capturing participants' experiences in RCTs and detecting possible latent benefits and risks. Such methods can detect latent target signals in novel therapy trials conducted in BD and generate novel hypotheses.

Evaluation of an online intervention for improving stroke survivors' health-related quality of life: A randomised controlled trial.

BACKGROUND: The aim of this trial was to evaluate the effectiveness of an online health behaviour change intervention-Prevent 2nd Stroke (P2S)-at improving health-related quality of life (HRQoL) amongst stroke survivors at 6 months of follow-up. METHODS AND FINDINGS: A prospective, blinded-endpoint randomised controlled trial, with stroke survivors as the unit of randomisation, was conducted between March 2018 and November 2019. Adult stroke survivors between 6 and 36 months post-stroke with capacity to use the intervention (determined by a score of ≥4 on the Modified Rankin Scale) and who had access and willingness to use the internet were recruited via mail-out invitations from 1 national and 1 regional stroke registry. Participants completed baseline (n = 399) and 6-month follow-up (n = 356; 89%) outcome assessments via computer-assisted telephone interviewing (CATI). At baseline the sample had an average age of 66 years (SD 12), and 65% were male. Randomisation occurred at the end of the baseline survey; CATI assessors and independent statisticians were blind to group allocation. The intervention group received remote access for a 12-week period to the online-only P2S program (n = 199; n = 28 lost at follow-up). The control group were emailed and posted a list of internet addresses of generic health websites (n = 200; n = 15 lost at follow-up). The primary outcome was HRQoL as measured by the EuroQol Visual Analogue Scale (EQ-VAS; self-rated global health); the outcome was assessed for differences between treatment groups at follow-up, adjusting for baseline measures. Secondary outcomes were HRQoL as measured by the EQ-5D (descriptive health state), diet quality, physical activity, alcohol consumption, smoking status, mood, physical functioning, and independent living. All outcomes included the variable 'stroke event (stroke/transient ischaemic attack/other)' as a covariate, and analysis was intention-to-treat. At 6 months, median EQ-VAS HRQoL score was significantly higher in the intervention group than the control group (85 vs 80, difference 5, 95% CI 0.79-9.21, p = 0.020). The results were robust to the assumption the data were missing at random; however, the results were not robust to the assumption that the difference in HRQoL between those with complete versus missing data was at least 3 points. Significantly higher proportions of people in the intervention group reported no problems with personal care (OR 2.17, 95% CI 1.05-4.48, p = 0.0359) and usual activities (OR 1.66, 95% CI 1.06-2.60, p = 0.0256) than in the control group. There were no significant differences between groups on all other secondary outcomes. The main limitation of the study is that the sample comprises mostly 'well' stroke survivors with limited to no disability. CONCLUSIONS: The P2S online healthy lifestyle program improved stroke survivors' self-reported global ratings of HRQoL (as measured by EQ-VAS) at 6-month follow-up. Online platforms represent a promising tool to engage and support some stroke survivors. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12617001205325.