Relative associations of behavioral and physiological risks for cardiometabolic disease with cognition in bipolar disorder during mid and later-life: findings from the UK biobank.

BACKGROUND: Cardiometabolic disease risk factors are disproportionately prevalent in bipolar disorder (BD) and are associated with cognitive impairment. It is, however, unknown which health risk factors for cardiometabolic disease are relevant to cognition in BD. This study aimed to identify the cardiometabolic disease risk factors that are the most important correlates of cognitive impairment in BD; and to examine whether the nature of the relationships vary between mid and later life. METHODS: Data from the UK Biobank were available for 966 participants with BD, aged between 40 and 69 years. Individual cardiometabolic disease risk factors were initially regressed onto a global cognition score in separate models for the following risk factor domains; (1) health risk behaviors (physical activity, sedentary behavior, smoking, and sleep) and (2) physiological risk factors, stratified into (2a) anthropometric and clinical risk (handgrip strength, body composition, and blood pressure), and (2b) cardiometabolic disease risk biomarkers (CRP, lipid profile, and HbA1c). A final combined multivariate regression model for global cognition was then fitted, including only the predictor variables that were significantly associated with cognition in the previous models. RESULTS: In the final combined model, lower mentally active and higher passive sedentary behavior, higher levels of physical activity, inadequate sleep duration, higher systolic and lower diastolic blood pressure, and lower handgrip strength were associated with worse global cognition. CONCLUSIONS: Health risk behaviors, as well as blood pressure and muscular strength, are associated with cognitive function in BD, whereas other traditional physiological cardiometabolic disease risk factors are not.

Substance use and posttraumatic stress disorder: 12-month outcomes among adults experiencing chronic homelessness in Australia.

INTRODUCTION: Substance use disorder and posttraumatic stress disorder (PTSD) are highly prevalent among individuals who experience homelessness. However, evaluations of interventions that combine housing and mental health services have reported inconsistent mental health and substance use outcomes when compared to usual services. We investigated 12-month change in substance use severity and PTSD symptom severity among adults experiencing chronic homelessness and tested whether observed differences were associated with housing, support from mental health services or the Journey to Social Inclusion (J2SI) program. METHODS: A randomised controlled trial compared the J2SI program with standard service provision (N = 135). Secondary analyses compared those who obtained housing or received mental health services with those who did not. Primary outcomes were alcohol and illicit substance use severity (alcohol, smoking and substance involvement screening test) and PTSD symptom severity (six-item PTSD checklist). RESULTS: There was significant improvement at 12 months in alcohol use severity, illicit substance use severity and PTSD symptoms in the overall sample. Having seen a mental health professional in the previous 12 months was associated with a significant reduction in alcohol and illicit substance use severity but was not associated with changes in PTSD symptom severity. Being housed at 12 months was associated with significantly higher alcohol use severity. DISCUSSION AND CONCLUSIONS: Findings highlight the importance of access to mental health care for people with a history of chronic homelessness. Research is needed to develop and test therapeutic and housing approaches to reduce PTSD symptom severity among people with experience of homelessness.

Arthroscopic hip surgery offers better early patient-reported outcome measures than targeted physiotherapy programs for the treatment of femoroacetabular impingement syndrome: a systematic review and meta-analysis of randomized controlled trials.

Targeted physiotherapy programs (TPP), and surgery, using either open surgical hip dislocation or hip arthroscopy (HA), are the treatment modalities available for femoroacetabular impingement syndrome (FAIS). Randomized controlled trials have recently been performed to compare these treatment options. This review was performed to provide a focused synthesis of the available evidence regarding the relative value of treatment options. A systematic search was performed of Medline, Embase, Cochrane Library and ClinicalTrials.gov databases. Inclusion criteria were randomized controlled trials comparing treatment methods. The Cochrane Risk of Bias assessment tool (RoB2) was used to assess the selected studies. A meta-analysis was performed between homogenous studies. Four trials were identified including 749 patients (392 males). The mean ages of the cohorts ranged between 30.1 and 36.2 years old. Three hundred thirty-five patients underwent HA by 46 surgeons among all trials. Fifty-two patients crossed over from the TPP to the HA group. One of the trials was found to have a high risk of bias, while the other three were between low risk and some concerns. The iHOT-33 was the most commonly used patient-reported outcome measure followed by the HOS ADL and EQ-5D-5L. Others scores were also identified. Scores from two trials could be pooled together for meta-analysis. Apart from SF-12 and GRC, all other scores have shown significantly better outcomes with HA in comparison to TPP at 8- and 12-months follow-up points. HA offers better patient-reported outcomes than TPP for management of FAIS at 8- and 12-months follow-up.

N-Acetylcysteine (NAC) in Schizophrenia Resistant to Clozapine: A Double-Blind, Randomized, Placebo-Controlled Trial Targeting Negative Symptoms.

BACKGROUND AND HYPOTHESIS: Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia, yet a significant proportion of individuals on clozapine continue to experience disabling symptoms, despite being treated with an adequate dose. There is a need for adjunct treatments to augment clozapine, notably for negative and cognitive symptoms. One such potential agent is the glutathione precursor N-acetylcysteine (NAC). STUDY DESIGN: A randomized double-blind, multi-center, placebo-controlled trial for clozapine patients with enduring psychotic symptoms (n = 84) was undertaken to investigate the efficacy of adjunctive NAC (2 g daily) for negative symptoms, cognition and quality of life (QoL). Efficacy was assessed at 8, 24, and 52 weeks. STUDY RESULTS: NAC did not significantly improve negative symptoms (P = .62), overall cognition (P = .71) or quality of life (Manchester quality of life: P = .11; Assessment of quality of life: P = .57) at any time point over a 1-year period of treatment. There were no differences in reported side effects between the groups (P = .26). CONCLUSIONS: NAC did not significantly improve schizophrenia symptoms, cognition, or quality of life in treatment-resistant patients taking clozapine. This trial was registered with "Australian and New Zealand Clinical Trials" on the 30 May, 2016 (Registration Number: ACTRN12615001273572).

Rehabilitation for atraumatic shoulder instability in circus arts performers: delivery via telehealth.

BACKGROUND: The Watson Instability Program (WIP1) is current best evidence for conservative management of atraumatic shoulder instability, but it is unknown if this program can be effectively delivered via tele-consultation. The purpose of this longitudinal pre-post intervention study was to determine the effects of the WIP1 on patient-reported outcome measures, scapular position, shoulder strength, and handstand stability in student circus performers with atraumatic shoulder instability when delivered via tele-consultation. METHODS: Student circus performers aged between 15 and 35 years from the National Institute of Circus Arts were recruited. A 12-week shoulder exercise program was delivered via tele-consultation during the Melbourne, Australia COVID-19 (coronavirus disease 2019) lockdown. The primary outcome measures were the Western Ontario Shoulder Instability Index score and the Melbourne Instability Shoulder Scale score. Secondary outcomes measures included the Orebro Musculoskeletal Pain Questionnaire, the Tampa Scale for Kinesiophobia, and physical assessment measures including strength via handheld dynamometry, scapular position using an inclinometer, and handstand stability via center-of-pressure fluctuation. Patient-reported outcomes were collected at baseline and 6-week, 12-week, 6-month, and 9-month time points, and physical outcomes were measured at baseline and 9-month time points. A repeated-measures mixed model (with effect sizes [ESs] and 95% confidence intervals [CIs]) was used to analyze patient-reported outcomes, handstand data, strength, and scapular measures. Significance was set at P < .05. RESULTS: Twenty-three student circus arts performers completed the study. Significant improvements were found in both Western Ontario Shoulder Instability Index scores (effect size [ES], 0.79 [95% CI, 0.31-1.33] at 6 weeks; ES, 1.08 [95% CI, 0.55-1.6] at 12 weeks; ES, 1.17 [95% CI, 0.62-1.78] at 6 months; and ES, 1.31 [95% CI, 0.74-1.95] at 9 months; P < .001) and Melbourne Instability Shoulder Scale scores (ES, 0.70 [95% CI, 0.22-1.22] at 6 weeks; ES, 0.83 [95% CI, 0.34-1.37] at 3 months; ES, 0.98 [95% CI, 0.46-1.54] at 6 months; and ES, 0.98 [95% CI, 0.43-1.50] at 9 months; P < .001), as well as Orebro Musculoskeletal Pain Questionnaire scores at all follow-up time points. The Tampa Scale for Kinesiophobia scores reached significance at 6 weeks and 12 weeks. Following rehabilitation, we found statistically significant increases in shoulder strength in all positions tested and increased scapular upward rotation measured at end-of-range abduction, as well as during loaded external rotation. The affected arm showed greater instability than the unaffected arm with a significant intervention effect on the affected arm showing a greater consistent anterior-posterior movement pattern. CONCLUSION: In a group of circus performers with atraumatic shoulder instability, treatment with the WIP1 via telehealth resulted in clinically and statistically significant improvements in shoulder symptoms and function.

The Demographic Representativeness and Health Outcomes of Digital Health Station Users: Longitudinal Study.

BACKGROUND: Digital health stations offer an affordable and accessible platform for people to monitor their health; however, there is limited information regarding the demographic profile of users and the health benefits of this technology. OBJECTIVE: This study aimed to assess the demographic representativeness of health station users, identify the factors associated with repeat utilization of stations, and determine if the health status of repeat users changed between baseline and final health check. METHODS: Data from 180,442 health station users in Australia, including 8441 repeat users, were compared with 2014-2015 Australian National Health Survey (NHS) participants on key demographic and health characteristics. Binary logistic regression analyses were used to compare demographic and health characteristics of repeat and one-time users. Baseline and final health checks of repeat users were compared using McNemar tests and Wilcoxon signed rank tests. The relationship between the number of checks and final health scores was investigated using generalized linear models. RESULTS: The demographic profile of SiSU health station users differs from that of the general population. A larger proportion of SiSU users were female (100,814/180,442, 55.87% vs 7807/15,393, 50.72%), younger (86,387/180,442, 47.88% vs 5309/15,393, 34.49% aged less than 35 years), and socioeconomically advantaged (64,388/180,442, 35.68% vs 3117/15,393, 20.25%). Compared with NHS participants, a smaller proportion of SiSU health station users were overweight or obese, were smokers, had high blood pressure (BP), or had diabetes. When data were weighted for demographic differences, only rates of high BP were found to be lower for SiSU users compared with the NHS participants (odds ratio [OR] 1.26; P<.001). Repeat users were more likely to be female (OR 1.37; P<.001), younger (OR 0.99; P<.001), and from high socioeconomic status areas-those residing in socioeconomic index for areas quintiles 4 and 5 were significantly more likely to be repeat users compared with those residing in quintile 1 (OR 1.243; P<.001 and OR 1.151; P<.001, respectively). Repeat users were more likely to have a higher BMI (OR 1.02; P<.001), high BP (OR 1.15; P<.001), and less likely to be smokers (OR 0.77; P<.001). Significant improvements in health status were observed for repeat users. Mean BMI decreased by 0.97 kg/m2 from baseline to final check (z=-14.24; P<.001), whereas the proportion of people with high BP decreased from 15.77% (1080/6848) to 12.90% (885/6860; χ21=38.2; P<.001). The proportion of smokers decreased from 11.91% (1005/8438) to 10.13% (853/8421; χ21=48.4; P<.001). Number of repeat health checks was significantly associated with smoking status (OR 0.96; P<.048) but not with higher BP (P=.14) or BMI (P=.23). CONCLUSIONS: These findings provide valuable insight into the benefits of health stations for self-monitoring and partially support previous research regarding the effect of demographics and health status on self-management of health.

Exploring the impact of providing men with information about potential prostate cancer treatment options prior to receiving biopsy results.

PURPOSE: There is little research assessing the impact of providing men with information about prostate cancer (PCa) treatment options at the time of referral for a prostate biopsy. Study objectives were to determine whether receiving an information booklet about PCa treatment options prior to receiving biopsy results was acceptable to patients, and if receiving this information influenced levels of anxiety, depression, distress, and treatment decisional conflict. METHODS: Between June 2016 and September 2017, a randomised block design was used to allocate patients from an Australian urology practice into the intervention or control group. Patients in the intervention group were provided with written information about treatment options for localised PCa prior to their biopsy. Outcome measures including the Distress Thermometer, Generalised Anxiety Disorder-7, Patient Health Questionnaire-9, and Decisional Conflict Scale were completed pre-biopsy and 2-3 weeks post-biopsy. Ninety-eight patients referred for an initial prostate biopsy for an elevated PSA test or suspicious digital rectal exam participated in the study (response rate = 78%). RESULTS: Multimodal repeated-measures analyses showed no significant differences between control and intervention groups in changes in distress, anxiety, or depression from pre- to post-biopsy, and in decisional conflict post-diagnosis (all p > .05). Thirty-five (87%) patients believed that the resource made it easier to understand subsequent explanation of treatment options, and 51 patients (98%) who received the intervention preferred to be given information at that time. CONCLUSIONS: Providing patients with information about treatment options prior to biopsy did not impact on changes in psychological distress and decisional conflict post-biopsy. However, the majority of patients preferred to be given such information at this time point.

Increasing Awareness of the Importance of Physical Activity and Healthy Nutrition: Results From a Mixed-Methods Evaluation of a Workplace Program.

BACKGROUND: To evaluate the impact of an online workplace program that promotes physical activity and health, while focusing on performance measures relating to physical activity, nutrition, and overall health. METHODS: The large sample size (more than 18,000 participants) allowed the use of text mining and machine-learning methods to determine what descriptions of the program identify successful outcomes, and hierarchical linear models to determine the most beneficial program modules and features. RESULTS: The program increased overall health and awareness of levels of physical activity and nutrition, especially for people who scored low on these measures initially. Interestingly, although physical activity is the most popular program module, the daily step-tracking process was associated with smaller improvements in overall health. CONCLUSIONS: This study finds that the Virgin Pulse Global Challenge is an effective workplace intervention for improving overall health and awareness of physical activity and nutrition. Effectiveness relates to the holistic approach adopted rather than to individual modules in isolation. Future evaluations of workplace health and exercise programs should explore a variety of outcome measures within the rich context provided by open-ended participant experience feedback. In addition, a control group and a follow-up study are required.

Quality of Life, Psychological Functioning, and Treatment Satisfaction of Men Who Have Undergone Penile Prosthesis Surgery Following Robot-Assisted Radical Prostatectomy.

BACKGROUND: Penile prosthesis surgery is last-line treatment to regaining erectile function after radical prostatectomy (RP) for localized prostate cancer. AIMS: To assess quality of life, psychological functioning, and treatment satisfaction of men who underwent penile implantation after RP; the psychosocial correlates of treatment satisfaction and sexual function after surgery; and the relation between patients' and partners' ratings of treatment satisfaction. METHODS: 98 consecutive patients who underwent penile implantation after RP from 2010 and 2015 and their partners were invited to complete a series of measures at a single time point. Of these, 71 patients and 43 partners completed measures assessing sexual function, psychological functioning, and treatment satisfaction. Proportions of patients who demonstrated good sexual function and satisfaction with treatment and clinical levels of anxiety and depression were calculated. Hierarchical regression analyses were conducted to determine psychosocial factors associated with patient treatment satisfaction and sexual function and patient-partner differences in treatment satisfaction. OUTCOMES: Patients completed the Expanded Prostate Cancer Index Composite Short Form (EPIC-26), Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), Prostate Cancer-Related Quality of Life Scale, Self-Esteem and Relationship Questionnaire (SEAR), Generalized Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-9 (PHQ-9). Partners completed the GAD-7, PHQ-9, EDITS (partner version), and SEAR. RESULTS: 94% of men reported satisfaction with treatment (EDITS score > 50). 77% of men reported good sexual function (EPIC-26 score > 60). Lower depression scores were associated with higher sexual confidence and sexual intimacy, and these were correlated with better treatment satisfaction and sexual function. Patients experienced higher sexual relationship satisfaction (median score = 90.6) than their partners (median score = 81.2), but there was no difference in treatment satisfaction between groups. Higher patient treatment satisfaction was more likely to be reported for couples whose depression scores were more similar. CLINICAL IMPLICATIONS: It is important to provide preoperative penile implant counseling and encourage patients to seek postoperative counseling if needed. STRENGTHS AND LIMITATIONS: This is one of the first Australian-based studies comprehensively assessing treatment satisfaction and psychosocial health of men after penile prosthesis surgery after RP. This was a retrospective cross-sectional study, so there is a possibility of recall bias, and causal associations could not be determined. CONCLUSION: Men in this Australian series who underwent penile prosthesis surgery after RP generally reported good sexual function and treatment satisfaction. Nevertheless, patient and partner mental health influenced their reported experience of the treatment. Pillay B, Moon D, Love C, et al. Quality of Life, Psychological Functioning, and Treatment Satisfaction of Men Who Have Undergone Penile Prosthesis Surgery Following Robot-Assisted Radical Prostatectomy. J Sex Med 2017;14:1612-1620.

An online psychological intervention can improve the sexual satisfaction of men following treatment for localized prostate cancer: outcomes of a Randomised Controlled Trial evaluating My Road Ahead.

BACKGROUND: Prostate cancer treatment often results in significant psycho-sexual challenges for men following treatment; however, many men report difficulty in accessing appropriate care. METHODS: A randomized controlled trial was undertaken to assess the efficacy of a 10-week self-guided online psychological intervention called My Road Ahead (MRA) for men with localized prostate cancer in improving sexual satisfaction. Participants were randomized to 1 of 3 conditions MRA alone or MRA plus online forum, or forum access alone. Pre, post, and follow-up assessments of overall sexual satisfaction were conducted. Mixed models and structural equation modeling were used to analyze the data. RESULTS: One hundred forty-two men (mean age 61 y; SD = 7) participated. The majority of participants had undergone radical prostatectomy (88%) and all men had received treatment for localized prostate cancer. Significant differences were obtained for the 3 groups (P = .026) and a significant improvement in total sexual satisfaction was observed only for participants who were allocated to MRA + forum with a large effect size (P = .004, partial η2  = 0.256). Structural equation modeling indicated that increases in sexual function, masculine self-esteem, and sexual confidence contributed significantly to overall sexual satisfaction for the MRA + forum plus forum condition. CONCLUSIONS: This study is the first, to our knowledge, that has evaluated a self-guided online psychological intervention tailored to the specific needs of men with prostate cancer. The findings indicate the potential for MRA to deliver support that men may not otherwise receive and also highlight the importance of psychological intervention to facilitate improved sexual outcomes.

N-acetylcysteine (NAC) in schizophrenia resistant to clozapine: a double blind randomised placebo controlled trial targeting negative symptoms.

BACKGROUND: Clozapine is an effective treatment for a proportion of people with schizophrenia (SZ) who are resistant to the beneficial effects of other antipsychotic drugs. However, anything from 40-60 % of people on clozapine experience residual symptoms even on adequate doses of the medication, and thus could be considered 'clozapine resistant'. Agents that could work alongside clozapine to improve efficacy whilst not increasing the adverse effect burden are both desired and necessary to improve the lives of individuals with clozapine-resistant SZ. N-Acetylcysteine (NAC) is one such possible agent. Previous research from our research group provided promising pilot data suggesting the efficacy of NAC in this patient population. The aim of the study reported here is to expand this work by conducting a large scale clinical trial of NAC in the treatment of clozapine-resistant SZ. METHODS: This study is an investigator initiated, multi-site, randomised, placebo-controlled trial. It aims to include 168 patients with clozapine-resistant SZ, divided into an intervention group (NAC) and a control group (placebo). Participants in the intervention group will receive 2 g daily of NAC. The primary outcome measures will be the negative symptom scores of the Positive and Negative Syndrome Scale (PANSS). Secondary outcome measures will include: changes in quality of life (QoL) as measured by the Lancashire Quality of Life Profile (LQoLP) and cognitive functioning as measured by the total score on the MATRICS. Additionally we will examine peripheral and cortical glutathione (GSH) concentrations as process outcomes. DISCUSSION: This large scale clinical trial will investigate the efficacy of NAC as an adjunctive medication to clozapine. This trial, if successful, will establish a cheap, safe and easy-to-use agent (NAC) as a 'go to' adjunct in patients that are only partly responsive to clozapine. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registration Number: Current Randomised Controlled Trial ACTRN12615001273572 . The date of registration 23 November 2015.

Fusing Data Mining, Machine Learning and Traditional Statistics to Detect Biomarkers Associated with Depression.

BACKGROUND: Atheoretical large-scale data mining techniques using machine learning algorithms have promise in the analysis of large epidemiological datasets. This study illustrates the use of a hybrid methodology for variable selection that took account of missing data and complex survey design to identify key biomarkers associated with depression from a large epidemiological study. METHODS: The study used a three-step methodology amalgamating multiple imputation, a machine learning boosted regression algorithm and logistic regression, to identify key biomarkers associated with depression in the National Health and Nutrition Examination Study (2009-2010). Depression was measured using the Patient Health Questionnaire-9 and 67 biomarkers were analysed. Covariates in this study included gender, age, race, smoking, food security, Poverty Income Ratio, Body Mass Index, physical activity, alcohol use, medical conditions and medications. The final imputed weighted multiple logistic regression model included possible confounders and moderators. RESULTS: After the creation of 20 imputation data sets from multiple chained regression sequences, machine learning boosted regression initially identified 21 biomarkers associated with depression. Using traditional logistic regression methods, including controlling for possible confounders and moderators, a final set of three biomarkers were selected. The final three biomarkers from the novel hybrid variable selection methodology were red cell distribution width (OR 1.15; 95% CI 1.01, 1.30), serum glucose (OR 1.01; 95% CI 1.00, 1.01) and total bilirubin (OR 0.12; 95% CI 0.05, 0.28). Significant interactions were found between total bilirubin with Mexican American/Hispanic group (p = 0.016), and current smokers (p<0.001). CONCLUSION: The systematic use of a hybrid methodology for variable selection, fusing data mining techniques using a machine learning algorithm with traditional statistical modelling, accounted for missing data and complex survey sampling methodology and was demonstrated to be a useful tool for detecting three biomarkers associated with depression for future hypothesis generation: red cell distribution width, serum glucose and total bilirubin.

The Diagnostic Validity and Reliability of an Internet-Based Clinical Assessment Program for Mental Disorders.

BACKGROUND: Internet-based assessment has the potential to assist with the diagnosis of mental health disorders and overcome the barriers associated with traditional services (eg, cost, stigma, distance). Further to existing online screening programs available, there is an opportunity to deliver more comprehensive and accurate diagnostic tools to supplement the assessment and treatment of mental health disorders. OBJECTIVE: The aim was to evaluate the diagnostic criterion validity and test-retest reliability of the electronic Psychological Assessment System (e-PASS), an online, self-report, multidisorder, clinical assessment and referral system. METHODS: Participants were 616 adults residing in Australia, recruited online, and representing prospective e-PASS users. Following e-PASS completion, 158 participants underwent a telephone-administered structured clinical interview and 39 participants repeated the e-PASS within 25 days of initial completion. RESULTS: With structured clinical interview results serving as the gold standard, diagnostic agreement with the e-PASS varied considerably from fair (eg, generalized anxiety disorder: κ=.37) to strong (eg, panic disorder: κ=.62). Although the e-PASS' sensitivity also varied (0.43-0.86) the specificity was generally high (0.68-1.00). The e-PASS sensitivity generally improved when reducing the e-PASS threshold to a subclinical result. Test-retest reliability ranged from moderate (eg, specific phobia: κ=.54) to substantial (eg, bulimia nervosa: κ=.87). CONCLUSIONS: The e-PASS produces reliable diagnostic results and performs generally well in excluding mental disorders, although at the expense of sensitivity. For screening purposes, the e-PASS subclinical result generally appears better than a clinical result as a diagnostic indicator. Further development and evaluation is needed to support the use of online diagnostic assessment programs for mental disorders. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN121611000704998; http://www.anzctr.org.au/trial_view.aspx?ID=336143 (Archived by WebCite at http://www.webcitation.org/618r3wvOG).

Preliminary results of a randomised controlled trial of an online psychological intervention to reduce distress in men treated for localised prostate cancer.

BACKGROUND: Prostate cancer (PCa) poses many emotional and physical challenges for men following treatment. The unmet support needs of these men are well documented, and access to psychosocial support remains problematic. OBJECTIVES: To assess the efficacy of an online psychological intervention for men who have localised PCa. DESIGN, SETTING, AND PARTICIPANTS: We undertook a randomised controlled trial to evaluate the intervention. Participants were randomly allocated to one of three conditions: My Road Ahead (MRA) alone (MRA Only), MRA plus access to an online forum (MRA+Forum), and access to the forum alone (Forum). INTERVENTION: The intervention was a 10-week self-guided online psychological intervention called My Road Ahead that consisted of six themed modules designed to facilitate improved emotional well-being in the context of PCa as well as a moderated peer forum. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Pre- and postintervention assessments of psychological distress (the 21-question Depression, Anxiety and Stress Scale) [1] and the Prostate Cancer-related Quality of Life scale [2] were conducted. Multivariate analysis of variance, regression, and structural equation modelling were used to analyse the data. RESULTS AND LIMITATIONS: In total, 142 participants were randomly allocated to one of the three intervention arms. The mean age of participants was 61 yr of age (standard deviation: 7), and 88% had undergone radical prostatectomy. A significant improvement in psychological distress was observed for participants who had access to the combined condition (MRA+Forum) with a moderate effect size (p=0.02; partial η(2)=0.07). In particular, the decline in the mean level of psychological distress was 8.8 units larger for the MRA+Forum group than the Forum group (95% confidence interval [CI], 0.9-16.7). Although the decline in the mean level of psychological distress was 7.0 units larger for the MRA+Forum group than for the MRA Only group, this difference was not significant (95% CI, 1.1-15.1). Structural equation modelling indicated that reductions in health worry and regret contributed significantly to the reductions in psychological distress for the MRA+Forum condition. CONCLUSIONS: This study is the first, to our knowledge, that has evaluated a self-guided online psychological intervention tailored to the specific needs of men who have PCa. The findings of this study indicate the potential for this programme to deliver support that men may not otherwise receive. PATIENT SUMMARY: This study found that men who have localised prostate cancer who received access to the online psychological intervention called My Road Ahead combined with the online peer discussion forum had significantly improved reductions in distress compared with those who received access to the online intervention alone or the forum alone.

Pretreatment attrition and formal withdrawal during treatment and their predictors: an exploratory study of the anxiety online data.

BACKGROUND: Although in its infancy, the field of e-mental health interventions has been gaining popularity and afforded considerable research attention. However, there are many gaps in the research. One such gap is in the area of attrition predictors at various stages of assessment and treatment delivery. OBJECTIVE: This exploratory study applied univariate and multivariate analysis to a large dataset provided by the Anxiety Online (now called Mental Health Online) system to identify predictors of attrition in treatment commencers and in those who formally withdrew during treatment based on 24 pretreatment demographic and personal variables and one clinical measure. METHODS: Participants were assessed using a complex online algorithm that resulted in primary and secondary diagnoses in accordance with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). Those who received a primary or secondary diagnosis of 1 of 5 anxiety disorders (generalized anxiety disorder, social anxiety disorder, obsessive-compulsive disorder, posttraumatic stress disorder, and panic disorder) were offered an online 12-week disorder-specific treatment program. RESULTS: Of 9394 potential participants, a total of 3880 clients enrolled and 5514 did not enroll in one of the treatment programs following the completion of pretreatment assessment measures (pretreatment attrition rate: 58.70%). A total of 3199 individuals did not formally withdraw from the 12-week treatment cycle, whereas 142 individuals formally dropped out (formal withdrawal during treatment dropout rate of 4.25%). The treatment commencers differed significantly (P<.001-.03) from the noncommencers on several variables (reason for registering, mental health concerns, postsecondary education, where first heard about Anxiety Online, Kessler-6 score, stage of change, quality of life, relationship status, preferred method of learning, and smoking status). Those who formally withdrew during treatment differed significantly (P=.002-.03) from those who did not formally withdraw in that they were less likely to express concerns about anxiety, stress, and depression; to rate their quality of life as very poor, poor, or good; to report adequate level of social support; and to report readiness to make or were in the process of making changes. CONCLUSIONS: This exploratory study identified predictors of pretreatment attrition and formal withdrawal during treatment dropouts for the Anxiety Online program. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN121611000704998; http://www.anzctr.org.au/trial_view.aspx?ID=336143 (Archived by WebCite at http://www.webcitation.org/618r3wvOG).

My Road Ahead study protocol: a randomised controlled trial of an online psychological intervention for men following treatment for localised prostate cancer.

BACKGROUND: There is a need for psychosocial interventions for men with prostate cancer to promote adaptive coping with the challenges and distress associated with diagnosis, treatment and recovery. In addition, interventions are needed that help to overcome barriers to psychosocial treatment such as limited face-to-face psychosocial support services, a shortage of adequately trained professionals, geographical distance, perceived and personal stigma and a preference for consumer-centric and self-directed learning. My Road Ahead is an online cognitive behaviour therapy (CBT) intervention for prostate cancer. This protocol describes a randomised controlled trial (RCT) that will evaluate the efficacy of this online intervention alone, the intervention in combination with a moderated online forum, and the moderated online forum alone. METHODS/DESIGN: This study utilises a RCT design with three groups receiving: 1) the 6-module My Road Ahead intervention alone; 2) the My Road Ahead intervention plus a moderated online forum; and 3) the moderated online forum alone. It is expected that 150 men with localised prostate cancer will be recruited into the RCT. Online measures will assess men's psychological distress as well as sexual and relationship adjustment at baseline, post-intervention, 3 month follow-up and 6 month follow-up. The study is being conducted in Australia and participants will be recruited from April 2012 to Feb 2014. The primary aim of this study is to evaluate the efficacy of My Road Ahead in reducing psychological distress. DISCUSSION: To our knowledge, My Road Ahead is the first self-directed online psychological intervention developed for men who have been treated for localised prostate cancer. The RCT will assess the efficacy of this intervention in improving psychological well-being, sexual satisfaction, relationship satisfaction and overall quality of life. If successful, this intervention could provide much needed support to men receiving treatment for localised prostate cancer in a highly accessible manner. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12611000278932.

Incorporation of OSI-7836 into DNA of Calu-6 and H460 xenograft tumors.

OSI-7836 (4'-thio-beta-D-arabinofuranosylcytosine) is a novel nucleoside analog in phase I clinical development for the treatment of cancer. As with other nucleoside analogs, the proposed mechanism of action involves phosphorylation to the triphosphate form followed by incorporation into cellular DNA, leading to cell death. This hypothesis has been examined by measuring and comparing the incorporation of ara-C, OSI-7836, and gemcitabine (dFdC) into DNA of cultured cells and by investigating the role of deoxycytidine kinase in OSI-7836 toxicity. We report here additional studies in which the role of cell cycling on OSI-7836 toxicity was investigated and incorporation of OSI-7836 into DNA of xenograft tumors measured. The role of the cell cycle was examined by comparing the toxicity of OSI-7836 in A549 NSCLC cells that were either in log phase growth or had reached confluence. A novel validated LC-MS/MS assay was developed to quantify the concentrations of OSI-7836 in DNA from Calu-6 and H460 human tumor xenografts in mice. Results showed that apoptosis induced by OSI-7836 was markedly greater in cycling cells than in confluent non-cycling cells despite only a modest increase in intracellular OSI-7836 triphosphate concentration. The LC-MS/MS assay developed to measure OSI-7836 incorporation into DNA had an on-column detection limit of 0.25 fmol, a quantification limit of 0.5 fmol, and a sensitivity of approximately 0.1 pmol OSI-7836/micromol dThy. Concentrations of OSI-7836 in splenic DNA (0.4 pmol OSI-7836/micromol dThy) averaged fivefold less than the average concentration in Calu-6 and H460 xenograft DNA (3.0 pmol OSI-7836/micromol dThy) following a 400 mg/kg dose of OSI-7836. Concentrations of OSI-7836 in Calu-6 tumor DNA isolated 24 h following a dose of 400, 1000, or 1600 mg OSI-7836/kg were approximately 1.3, 1 and 1.3 pmol OSI-7836/micromol dThy, respectively. Concentrations of OSI-7836 in DNA from H460 and Calu-6 xenografts did not appear to increase during repeated administration of 400 mg OSI-7836/kg on days 1, 4, 7, and 10. The majority of OSI-7836 in DNA from Calu-6 and H460 tumors of mice dosed with 1600 mg/kg was located at internal nucleotide linkages, similar to dFdC and ara-C. In conclusion, cell cycling studies supported the hypothesis that OSI-7836 cytotoxicity is dependent upon DNA synthesis. A validated LC-MS/MS assay was developed that could quantify OSI-7836 in DNA from tissues. The assay was used to show that OSI-7836 was incorporated in internal linkages in tumor DNA in a manner that was dose-independent at the doses tested and did not appear to accumulate during repeated dosing. The results suggest that if DNA incorporation is a toxic event, the relationships between administered dose, DNA incorporation, and toxicity are complex.

OSI-211, a novel liposomal topoisomerase I inhibitor, is active in SCID mouse models of human AML and ALL.

OSI-211 (liposomal lurtotecan), was evaluated using several different dose schedules (1mg/kg, d1-5, 1.75 mg/kg d1, 3, 5 and 6 mg/kg d1, 8) in severe combined immunodeficient (SCID) mouse models of acute myelogenous leukemia (AML) and acute lymphocytic leukemia (ALL) with early treatment (ET, days 6-8) or late treatment (LT, days 15-19), examining early and advanced disease, respectively. Due to the aggressive nature of the Molt-4 model, the ET and LT were accelerated to day 3 or 4 and day 8 post-implant, respectively. For each model, 2 x 10(7) (KBM-3B) or 1 x 10(7) (Molt-4, HL-60 and CEM) leukemia cells were injected intravenously into the tail vein. Each control and test group consisted of eight animals. All three schedules (1mg/kg qd1-5, 1.75 mg/kg d1, 3, 5 and 6 mg/kg d1, 8) increased the life span of OSI-211 treated animals in each model, with a tendency toward improved efficacy with the 6 mg/kg d1, 8 schedule. As a result, the activity of the 6 mg/kg d1, 8 schedule is detailed for each model. ET significantly (P<0.005) increased survival in the KBM-3B model with 86% long-term survivors (LTS). Using PRC analysis, human beta-globin gene sequences in one or several tissues were amplified in all but 3 LTS, suggesting minimal residual disease in 26 of the 29 LTS. LT also significantly (P<0.005) improved average life span in the KBM-3B model, with an average ILS=196+/-11% and one LTS. Treatment of HL-60 leukemia animals significantly (P<0.005) increased life span, with an ILS=213+/-9% and two LTS for ET, and with an ILS=219+/-4% and no LTS for LT. Treatment of Molt-4 animals, the most aggressive leukemia model tested, significantly (P<0.005) increased life span, with an average ILS=181+/-3% and no LTS for ET and an average ILS=172+/-1% with no LTS for LT. In the CEM model, ET resulted in a significantly (P<0.005) improved ILS=244+/-24% with one LTS. In comparison to OSI-211, treatment with DaunoXome, the liposomal formulation of daunorubicin, a drug with clinical efficacy in AML and ALL, had no effect on survival in the KBM-3B, nor Molt-4 A4 leukemia models when administered at its maximum or near maximum tolerated doses of 3mg/kg d1, 8. These data demonstrate that OSI-211 has potent antileukemia activity in preclinical SCID mouse AML and ALL leukemia models, supporting the clinical investigation of OSI-211 for hematological malignancies.