Online insomnia treatment and the reduction of anxiety symptoms as a secondary outcome in a randomised controlled trial: The role of cognitive-behavioural factors.

OBJECTIVE: Insomnia and anxiety commonly co-occur, yet the mechanisms underlying this remain unclear. The current paper describes the impact of an Internet-based intervention for insomnia on anxiety, and explores the influence of two cognitive-behavioural constructs - dysfunctional beliefs about sleep and sleep-threat monitoring. METHODS: A large-scale, 9-week, two-arm randomised controlled trial ( N = 1149) of community-dwelling Australian adults with insomnia and elevated yet subclinical depression symptoms was conducted, comparing a cognitive behavioural therapy-based online intervention for insomnia (Sleep Healthy Using The Internet) with an attention-matched online control intervention (HealthWatch). Symptoms of anxiety were assessed at pretest, posttest, and 6-month follow-up. Dysfunctional beliefs about sleep and sleep threat monitoring were assessed only at pretest. RESULTS: Sleep Healthy Using The Internet led to a greater reduction in anxiety symptoms at both posttest ( t724.27 = -6.77, p < 0.001) and at 6-month follow-up ( t700.67 = -4.27, p < 0.001) than HealthWatch. At posttest and follow-up, this effect was found to moderated by sleep-threat monitoring ( t713.69 = -2.39, p < 0.05 and t694.77 = -2.98, p < 0.01 respectively) but not by dysfunctional beliefs about sleep at either posttest or follow-up ( t717.53 = -0.61, p = 0.55 and t683.79 = 0.22, p = 0.83 respectively). Participants in the Sleep Healthy Using The Internet condition with higher levels of sleep-threat monitoring showed a greater reduction in anxiety than those with lower levels from pretest to posttest, ( t724.27 = -6.77, p < 0.001) and through to 6-month follow-up ( t700.67 = -4.27, p < 0.001). This result remained after controlling for baseline anxiety levels. CONCLUSION: The findings suggest that online cognitive behavioral therapy interventions for insomnia are beneficial for reducing anxiety regardless of people's beliefs about their sleep and insomnia, and this is particularly the case for those with high sleep-threat monitoring. This study also provides further evidence for cognitive models of insomnia.

Effectiveness of a Web-Based Self-Help Program for Suicidal Thinking in an Australian Community Sample: Randomized Controlled Trial.

BACKGROUND: Treatment for suicidality can be delivered online, but evidence for its effectiveness is needed. OBJECTIVE: The goal of our study was to examine the effectiveness of an online self-help intervention for suicidal thinking compared to an attention-matched control program. METHODS: A 2-arm randomized controlled trial was conducted with assessment at postintervention, 6, and, 12 months. Through media and community advertizing, 418 suicidal adults were recruited to an online portal and were delivered the intervention program (Living with Deadly Thoughts) or a control program (Living Well). The primary outcome was severity of suicidal thinking, assessed using the Columbia Suicide Severity Rating Scale. RESULTS: Intention-to-treat analyses showed significant reductions in the severity of suicidal thinking at postintervention, 6, and 12 months. However, no overall group differences were found. CONCLUSIONS: Living with Deadly Thoughts was of no greater effectiveness than the control group. Further investigation into the conditions under which this program may be beneficial is now needed. Limitations of this trial include it being underpowered given the effect size ultimately observed, a high attrition rate, and the inability of determining suicide deaths or of verifying self-reported suicide attempts. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12613000410752; https://www.anzctr.org.au/ Trial/Registration/TrialReview.aspx?id=364016 (Archived by WebCite at http://www.webcitation.org/6vK5FvQXy); Universal Trial Number U1111-1141-6595.

Trajectories of change and long-term outcomes in a randomised controlled trial of internet-based insomnia treatment to prevent depression.

BACKGROUND: Insomnia treatment using an internet-based cognitive-behavioural therapy for insomnia (CBT-I) program reduces depression symptoms, anxiety symptoms and suicidal ideation. However, the speed, longevity and consistency of these effects are unknown. AIMS: To test the following: whether the efficacy of online CBT-I was sustained over 18 months; how rapidly the effects of CBT-I emerged; evidence for distinct trajectories of change in depressive symptoms; and predictors of these trajectories. METHOD: A randomised controlled trial compared the 6-week Sleep Healthy Using the Internet (SHUTi) CBT-I program to an attention control program. Adults (N=1149) with clinical insomnia and subclinical depression symptoms were recruited online from the Australian community. RESULTS: Depression, anxiety and insomnia decreased significantly by week 4 of the intervention period and remained significantly lower relative to control for >18 months (between-group Cohen's d=0.63, 0.47, 0.55, respectively, at 18 months). Effects on suicidal ideation were only short term. Two depression trajectories were identified using growth mixture models: improving (95%) and stable/deteriorating (5%) symptoms. More severe baseline depression, younger age and limited comfort with the internet were associated with reduced odds of improvement. CONCLUSIONS: Online CBT-I produced rapid and long-term symptom reduction in people with subclinical depressive symptoms, although the initial effect on suicidal ideation was not sustained. DECLARATION OF INTEREST: P.J.B. has received grants from the National Health and Medical Research Council (NHMRC) during the conduct of the study. H.C. has received grants from the NHMRC and the Australian Research Council during the conduct of the study. L.M.R. receives research funding from the National Institutes of Health (NIH) that, in part, focuses on insomnia. F.P.T. and L.M.R. have equity ownership in BeHealth Solutions (Charlottesville, VA, USA), a company that develops and makes available products related to the research reported in this manuscript. BeHealth Solutions has licensed the SHUTi program and the software platform on which it was built from the University of Virginia. The terms of this arrangement have been reviewed and approved by the University of Virginia in accordance with its conflict of interest policy. N.G. has received grants from the NHMRC during the conduct of the study and personal fees from Lundbeck, Servier and Janssen outside the submitted work. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

Effectiveness of an online insomnia program (SHUTi) for prevention of depressive episodes (the GoodNight Study): a randomised controlled trial.

BACKGROUND: In view of the high co-occurrence of depression and insomnia, a novel way to reduce the risk of escalating depression might be to offer an insomnia intervention. We aimed to assess whether an online self-help insomnia program could reduce depression symptoms. METHODS: We did this randomised controlled trial at the Australian National University in Canberra, Australia. Internet users (aged 18-64 years) with insomnia and depression symptoms, but who did not meet criteria for major depressive disorder, were randomly assigned (1:1), via computer-generated randomisation, to receive SHUTi, a 6 week, modular, online insomnia program based on cognitive behavioural therapy for insomnia, or HealthWatch, an interactive, attention-matched, internet-based placebo control program. Randomisation was stratified by age and sex. Telephone-based interviewers, statisticians, and chief investigators were masked to group allocation. The primary outcome was depression symptoms at 6 months, as measured with the Patient Health Questionnaire (PHQ-9). The primary analysis was by intention to treat. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12611000121965. FINDINGS: Between April 30, 2013, and June 9, 2014, we randomly assigned 1149 participants to receive SHUTi (n=574) or HealthWatch (n=575), of whom 581 (51%) participants completed the study program assessments at 6 weeks and 504 (44%) participants completed 6 months' follow-up. SHUTi significantly lowered depression symptoms on the PHQ-9 at 6 weeks and 6 months compared with HealthWatch (F[degrees of freedom 2,640·1]=37·2, p<0·0001). Major depressive disorder was diagnosed in 22 (4%) participants at 6 months (n=9 in the SHUTi group and n=13 in the HealthWatch group), with no superior effect of SHUTi versus HealthWatch (Fisher's exact test=0·52; p=0·32). No adverse events were reported. INTERPRETATION: Online cognitive behaviour therapy for insomnia treatment is a practical and effective way to reduce depression symptoms and could be capable of reducing depression at the population level by use of a fully automatised system with the potential for wide dissemination. FUNDING: Australian National Health and Medical Research Council.

Reducing suicidal thoughts in the Australian general population through web-based self-help: study protocol for a randomized controlled trial.

BACKGROUND: Suicidal thoughts are common in the general population, causing significant disability. However, a substantial number of people struggling with suicidality do not access appropriate services. Online self-help may help overcome barriers to help-seeking. This study aims to examine the effectiveness of an online self-help program targeted at reducing suicidal thoughts compared with an attention-matched control condition in the Australian adult population. This trial is based on a Dutch self-help program, which was found to be effective in reducing suicidal thoughts. METHODS/DESIGN: A total of 570 community-dwelling adults (18 to 65 years old) with suicidal thoughts will be recruited via various media and randomly assigned to the 6-week online program aimed at reducing suicidal thoughts or a 6-week attention-matched control program. Primary outcome measure is the severity of suicidal thoughts. Secondary outcome measures include suicide plans, capacity to cope with suicidal thoughts, reasons for living, symptoms of depression, hopelessness, anxiety/worry, rumination, panic, perceived burdensomeness and thwarted belongingness, acquired capability, alcohol consumption, insomnia, and various cost-effectiveness measures. DISCUSSION: Although the original Dutch trial found web-based self-help to be effective in reducing suicidal thoughts, randomized controlled trials (RCT) of online programs for suicidal thoughts are rare. The present study extends previous research by running the first English language RCT of this sort. As a result of the original study, the current RCT includes refinements to the design, including greater levels of participant anonymity and longer follow-up periods. Limitations of this trial include the potential for high drop-out and the inability to ascertain whether any suicides occur during the study. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) Registration number: ACTRN12613000410752 (15 April 2013). Universal Trial Number (UTN): U1111-1141-6595 (15 April 2013).

The influence of job stress, social support and health status on intermittent and chronic sleep disturbance: an 8-year longitudinal analysis.

OBJECTIVE: To determine the role of health status and social support in the relationship between job stress and sleep disturbance, for both intermittent and chronic sleep disturbance. METHODS: A total of 1946 mid-life adults completed three questionnaires spanning an 8-year time frame. Sleep disturbance was assessed at each time point, and participants were classified as experiencing intermittent, chronic or no sleep disturbance across this 8-year period. Independent variables included a range of job stress measures, social support, physical and mental health, and demographic characteristics. RESULTS: After controlling for physical and mental health, perceived lack of job marketability increased risk of intermittent sleep disturbance (odds ratio (OR)=1.33, p=0.012). No other job stress measures were associated with either intermittent or chronic sleep disturbance after adjusting for years of education, social support, and employment status. Poorer mental and physical health status, although significantly increasing odds for intermittent sleep disturbance, represented a significantly greater increase in the odds for chronic sleep disturbance over and above intermittent disturbance (OR=0.96, p<0.001 for both SF-12 mental and physical health). CONCLUSION: This population-based cohort study found little evidence that job stress had an independent effect on chronic or intermittent sleep disturbance independent of health, social support, and education. Risk profiles for intermittent and chronic sleep disturbance did not differ with regard to job stress; however, various demographic and social support factors were distinguishing factors. Health status, both physical and mental, also showed a significantly greater impact on chronic sleep disturbance than intermittent sleep disturbance. Karasek's model of job strain had little value in predicting sleep disturbance outcomes.

The GoodNight study--online CBT for insomnia for the indicated prevention of depression: study protocol for a randomised controlled trial.

BACKGROUND: Cognitive Behaviour Therapy for Insomnia (CBT-I) delivered through the Internet is effective as a treatment in reducing insomnia in individuals seeking help for insomnia. CBT-I also lowers levels of depression in this group. However, it is not known if targeting insomnia using CBT-I will lower depressive symptoms, and thus reduce the risk of major depressive episode onset, in those specifically at risk for depression. Therefore, this study aims to examine whether Internet delivery of fully automated self-help CBT-I designed to reduce insomnia will prevent depression. METHOD/DESIGN: A sample of 1,600 community-dwelling adults (aged 18-64), who screen positive for both subclinical levels of depressive symptoms and insomnia, will be recruited via various media and randomised to either a 9-week online insomnia treatment programme, Sleep Healthy Using The internet (SHUTi), or an online attention-matched control group (HealthWatch). The primary outcome variable will be depression symptom levels at the 6-month post-intervention on the Patient Heath Questionnaire-9 (PHQ-9). A secondary outcome will be onset of major depressive episodes assessed at the 6-month post-intervention using 'current' and 'time from intervention' criteria from the Mini International Neuropsychiatric Interview. DISCUSSION: This trial is the first randomised controlled trial of an Internet-based insomnia intervention as an indicated preventative programme for depression. If effective, online provision of a depression prevention programme will facilitate dissemination. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR), Registration number: ACTRN12611000121965.

Cognitive-behavioural factors that predict sleep disturbance 4 years later.

OBJECTIVE: Cognitive models have identified a number of factors that maintain sleep disturbance. It is unknown whether similar factors lead to initial onset. This study tested whether three cognitive-behavioural factors: ruminative style, somatic sensitivity, and behavioural avoidance predicted sleep disturbance onset at four-year follow-up. METHODS: Participants (n=4,042) were assessed using a) a composite measure of Somatic Sensitivity, b) the Ruminative Style Scale, c) the Behavioural Inhibition Scale of the BISBAS and d) sleep-related items from the Goldberg Depression and Anxiety Scale. RESULTS: Sleep disturbance at 4 years was significantly predicted by all three cognitive-behavioural factors--somatic sensitivity, ruminative style and behavioural avoidance--and, in the final analysis, was independently predicted by somatic sensitivity (OR=1.427, p<0.001) and ruminative style (OR=1.035, p=0.002). CONCLUSION: This study tested whether three cognitive-behavioural factors: ruminative style, somatic sensitivity, and behavioural avoidance were predictive of the onset of sleep disturbance after 4 years. Although all three factors were significantly associated with the onset of sleep disturbance, only ruminative style and somatic sensitivity were found to independently predict sleep disturbance, supporting these constructs as predisposing cognitive-behavioural risk factors.

Implication of Wt1 in the pathogenesis of nephrogenic failure in a mouse model of retinoic acid-induced caudal regression syndrome.

Renal malformations are common human birth defects that sometimes occur in the context of the caudal regression syndrome. Here, we found that exposure of pregnant mice to all-trans retinoic acid, at a time when the metanephros has yet to form, causes a failure of kidney development along with caudal regression. Maternal treatment with Am580 (retinoic acid receptor alpha agonist) also induced similar patterns of kidney maldevelopment in the fetus. In metanephroi from retinoic acid-treated pregnancies, renal mesenchyme condensed around the ureteric bud but then failed to differentiate into nephrons, instead undergoing involution by fulminant apoptosis to produce a renal agenesis phenotype. Results of whole organ cultures in serum-free medium, and also tissue recombination experiments, showed that the nephrogenic defect was intrinsic to the kidney and that it resided in the metanephric mesenchyme and not the ureteric bud. Renal mesenchyme from control embryos expressed Wilms' tumor 1 (Wt1), but this transcription factor, which is indispensable for kidney development, failed to express in metanephroi of retinoic acid-exposed embryos. Wt1 expression and organogenesis were both restored, however, when metanephroi from retinoic acid-treated pregnancies were grown in serum-containing media. Our data illuminate the pathobiology of a severe, teratogen-induced kidney malformation.

Ultrastructure of the bladder in classic exstrophy: correlation with development of continence.

PURPOSE: Successful initial surgical management of bladder exstrophy does not always lead to continence. We evaluated the ultrastructure of the exstrophic bladder using electron microscopy (EM) at various stages of reconstruction to determine whether morphology could correlate with the potential for continence. MATERIALS AND METHODS: Bladder specimens obtained from 32 patients undergoing various stages of exstrophy reconstruction were evaluated by EM. Specimens were obtained at primary newborn closure (group 1-10), reclosure following failure (group 2-2), bladder neck reconstruction (group 3-9) and augmentation cystoplasty (group 4-11). Evaluation was performed by a single anatomist with experience with EM. Biopsies were separated into those with good, intermediate or poor ultrastructural parameters and then correlated clinically. RESULTS: In group 1, 4 children had good and 2 had intermediate parameters. All showed increased bladder volumes at followup. Four patients had poor parameters and poor bladder growth. The 2 group 2 children had poor parameters and bladder growth. In group 3, 7 of 9 patients had good and 1 had intermediate parameters. Eight of the 9 patients are doing well. Only 3 of the 11 group 4 children had good parameters and an additional 2 had intermediate parameters. CONCLUSIONS: Ultrastructural evaluation can identify changes in the bladder that may portend a poor prognosis for eventual continence. Although the correlation was good at bladder closure, some patients with good parameters still had failed reconstruction. Since this is a small study, we continue to recommend reconstruction in all patients who have an adequate bladder template.