Thomas Hamborg

Effectiveness of a Web-Based Cognitive-Behavioral Tool to Improve Mental Well-Being in the General Population: Randomized Controlled Trial

Background Interventions to promote mental well-being can bring benefits to the individual and to society. The Internet can facilitate the large-scale and low-cost delivery of individually targeted health promoting interventions. Objective To evaluate the effectiveness of a self-directed Internet-delivered cognitive-behavioral skills training tool in improving mental well-being in a population sample. Methods This was a randomized trial with a waiting-list control. Using advertisements on a national health portal and through its mailing list, we recruited 3070 participants aged 18 or over, resident in England, and willing to give their email address and access a fully automated Web-based intervention. The intervention (MoodGYM) consisted of 5 interactive modules that teach cognitive-behavioral principles. Participants in the intervention arm received weekly email reminders to access the intervention. The control group received access to the intervention after the trial was completed and received no specific intervention or email reminders. Outcomes were assessed by using self-completion questionnaires. The primary outcome was mental well-being measured with the Warwick-Edinburgh Mental Well-being Scale (WEMWBS). Secondary outcomes were Center for Epidemiologic Studies Depression scale (CES-D) depression scores, Generalized Anxiety Disorder 7-item scale (GAD-7) anxiety scores, EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D) quality of life scores, physical activity, and health service use. All outcomes were measured at baseline, and at 6- and 12-week follow-ups. Results A total of 1529 (49.80%) participants completed final follow-up at 12 weeks. Retention was 73.11% (1123/1536) in the control arm and 26.47% (406/1534) in the intervention arm. No relationship between baseline measures and withdrawal could be established. The analysis of WEMWBS mental well-being scores using a linear mixed model for repeated measures showed no difference between intervention and control group at baseline (difference –0.124 points, 95% CI –0.814 to 0.566), and significant improvements for the intervention group at 6 weeks (2.542 points, 95% CI 1.693-3.390) and at 12 weeks (2.876 points, 95% CI 1.933-3.819). The model showed a highly significant (P<.001) intervention by time interaction effect. There were also significant improvements in self-rated scores of depression and anxiety. Given the high level of attrition, a sensitivity analysis with imputed missing values was undertaken that also showed a significant positive effect of the intervention. Conclusions Participants allocated to the intervention arm had an average increase of approximately 3 points on the WEMWBS scale compared to no increase for participants in the control group. Three points on this scale is approximately one-third of a standard deviation. In a low-cost automated intervention designed to shift the population distribution of mental well-being, a small difference per individual could yield a major benefit in population terms. In common with other Web-based interventions, there were high rates of attrition. Further work is needed to improve acceptability, to evaluate against placebo effect, and to disaggregate the effect on mental well-being from the effect on depression and anxiety. Trial Registration International Standard Randomised Controlled Trial Number Register ISRCTN 48134476; http://www.controlled-trials.com/ISRCTN48134476 (Archived by WebCite® at http://www.webcitation.org/6DFgW2p3Q)

The changing face of cardiovascular disease 2000–2012: An analysis of the world health organisation global health estimates data

The pattern and global burden of disease has evolved considerably over the last two decades, from primarily communicable, maternal, and perinatal causes to non-communicable disease (NCD). Cardiovascular disease (CVD) has become the single most important and largest cause of NCD deaths worldwide at over 50%. The World Health Organisation (WHO) estimates that 17.6 million people died of CVD worldwide in 2012. Proportionally, this accounts for an estimated 31.43% of global mortality, with ischaemic heart disease (IHD) accounting for approximately 7.4 million deaths, 13.2% of the total. IHD was also the greatest single cause of death in 2000, accounting for an estimated 6.0 million deaths. The global burden of CVD falls, principally, on the low and middle-income (LMI) countries, accounting for over 80% of CVD deaths. Individual populations face differing challenges and each population has unique health burdens, however, CVD remains one of the greatest health challenges both nationally and worldwide.

Adaptive Designs for Confirmatory Clinical Trials with Subgroup Selection

Growing interest in stratified medicine is leading to increasing importance of subgroup analyses in confirmatory clinical trials. Conventionally, confirmatory clinical trials either focus on a subgroup identified in advance or assess subgroup effects once the trial is completed. The focus of this article is methodology for adaptive clinical trials that both identify whether a treatment is particularly effective in a predefined subgroup, potentially enabling alteration of recruitment, and assess the effectiveness in the subgroup and/or whole population. Methods for such adaptive trials are described and compared, and the logistical and regulatory issues associated with such approaches are discussed.

Predicting maintenance of attendance at walking groups: Testing constructs from three leading maintenance theories.

OBJECTIVE Little is known about the processes and factors that account for maintenance, with several theories existing that have not been subject to many empirical tests. The aim of this study was to test how well theoretical constructs derived from the Health Action Process Approach, Rothmans theory of maintenance, and Verplankens approach to habitual behavior predicted maintenance of attendance at walking groups. METHOD 114 participants, who had already attended walking groups in the community for at least 3 months, completed a questionnaire assessing theoretical constructs regarding maintenance. An objective assessment of attendance over the subsequent 3 months was gained. Multilevel modeling was used to predict maintenance, controlling for clustering within walking groups. RESULTS Recovery self-efficacy predicted maintenance, even after accounting for clustering. Satisfaction with social outcomes, satisfaction with health outcomes, and overall satisfaction predicted maintenance, but only satisfaction with health outcomes significantly predicted maintenance after accounting for clustering. Self-reported habitual behavior did not predict maintenance despite mean previous attendance being 20.7 months. CONCLUSIONS Recovery self-efficacy, and satisfaction with health outcomes of walking group attendance appeared to be important for objectively measured maintenance, whereas self-reported habit appeared not to be important for maintenance at walking groups. The findings suggest that there is a need for intervention studies to boost recovery self-efficacy and satisfaction with outcomes of walking group attendance, to assess impact on maintenance.

Functional Cardiovascular Reserve Predicts Survival Pre-Kidney and Post-Kidney Transplantation

Exercise intolerance is an important comorbidity in patients with CKD. Anaerobic threshold (AT) determines the upper limits of aerobic exercise and is a measure of cardiovascular reserve. This study investigated the prognostic capacity of AT on survival in patients with advanced CKD and the effect of kidney transplantation on survival in those with reduced cardiovascular reserve. Using cardiopulmonary exercise testing, cardiovascular reserve was evaluated in 240 patients who were waitlisted for kidney transplantation between 2008 and 2010, and patients were followed for ≤5 years. Survival time was the primary endpoint. Cumulative survival for the entire cohort was 72.6% (24 deaths), with cardiovascular events being the most common cause of death (54.2%). According to Kaplan-Meier estimates, patients with AT <40% of predicted peak VO2 had a significantly reduced 5-year cumulative overall survival rate compared with those with AT ≥40% (P<0.001). Regarding the cohort with AT <40%, patients who underwent kidney transplantation (6 deaths) had significantly better survival compared with nontransplanted patients (17 deaths) (hazard ratio, 4.48; 95% confidence interval, 1.78 to 11.38; P=0.002). Survival did not differ significantly among patients with AT ≥40%, with one death in the nontransplanted group and no deaths in the transplanted group. In summary, this is the first prospective study to demonstrate a significant association of AT, as the objective index of cardiovascular reserve, with survival in patients with advanced CKD. High-risk patients with reduced cardiovascular reserve had a better survival rate after receiving a kidney transplant.

A high-fidelity virtual environment for the study of paranoia

Psychotic disorders carry social and economic costs for sufferers and society. Recent evidence highlights the risk posed by urban upbringing and social deprivation in the genesis of paranoia and psychosis. Evidence based psychological interventions are often not offered because of a lack of therapists. Virtual reality (VR) environments have been used to treat mental health problems. VR may be a way of understanding the aetiological processes in psychosis and increasing psychotherapeutic resources for its treatment. We developed a high-fidelity virtual reality scenario of an urban street scene to test the hypothesis that virtual urban exposure is able to generate paranoia to a comparable or greater extent than scenarios using indoor scenes. Participants (n = 32) entered the VR scenario for four minutes, after which time their degree of paranoid ideation was assessed. We demonstrated that the virtual reality scenario was able to elicit paranoia in a nonclinical, healthy group and that an urban scene was more likely to lead to higher levels of paranoia than a virtual indoor environment. We suggest that this study offers evidence to support the role of exposure to factors in the urban environment in the genesis and maintenance of psychotic experiences and symptoms. The realistic high-fidelity street scene scenario may offer a useful tool for therapists.

Decision-theoretic designs for small trials and pilot studies : A review

Pilot studies and other small clinical trials are often conducted but serve a variety of purposes and there is little consensus on their design. One paradigm that has been suggested for the design of such studies is Bayesian decision theory. In this article, we review the literature with the aim of summarizing current methodological developments in this area. We find that decision-theoretic methods have been applied to the design of small clinical trials in a number of areas. We divide our discussion of published methods into those for trials conducted in a single stage, those for multi-stage trials in which decisions are made through the course of the trial at a number of interim analyses, and those that attempt to design a series of clinical trials or a drug development programme. In all three cases, a number of methods have been proposed, depending on the decision maker’s perspective being considered and the details of utility functions that are used to construct the optimal design.

Reduced functional measure of cardiovascular reserve predicts admission to critical care unit following kidney transplantation

Background There is currently no effective preoperative assessment for patients undergoing kidney transplantation that is able to identify those at high perioperative risk requiring admission to critical care unit (CCU). We sought to determine if functional measures of cardiovascular reserve, in particular the anaerobic threshold (VO2AT) could identify these patients. Methods Adult patients were assessed within 4 weeks prior to kidney transplantation in a University hospital with a 37-bed CCU, between April 2010 and June 2012. Cardiopulmonary exercise testing (CPET), echocardiography and arterial applanation tonometry were performed. Results There were 70 participants (age 41.7±14.5 years, 60% male, 91.4% living donor kidney recipients, 23.4% were desensitized). 14 patients (20%) required escalation of care from the ward to CCU following transplantation. Reduced anaerobic threshold (VO2AT) was the most significant predictor, independently (OR = 0.43; 95% CI 0.27–0.68; p<0.001) and in the multivariate logistic regression analysis (adjusted OR = 0.26; 95% CI 0.12–0.59; p = 0.001). The area under the receiver-operating-characteristic curve was 0.93, based on a risk prediction model that incorporated VO2AT, body mass index and desensitization status. Neither echocardiographic nor measures of aortic compliance were significantly associated with CCU admission. Conclusions To our knowledge, this is the first prospective observational study to demonstrate the usefulness of CPET as a preoperative risk stratification tool for patients undergoing kidney transplantation. The study suggests that VO2AT has the potential to predict perioperative morbidity in kidney transplant recipients.

High-intensity interval training versus moderate-intensity steady-state training in UK cardiac rehabilitation programmes (HIIT or MISS UK): study protocol for a multicentre randomised controlled trial and economic evaluation

Introduction Current international guidelines for cardiac rehabilitation (CR) advocate moderate-intensity exercise training (MISS, moderate-intensity steady state). This recommendation predates significant advances in medical therapy for coronary heart disease (CHD) and may not be the most appropriate strategy for the ‘modern’ patient with CHD. High-intensity interval training (HIIT) appears to be a safe and effective alternative, resulting in greater improvements in peak oxygen uptake (VO2 peak). To date, HIIT trials have predominantly been proof-of-concept studies in the laboratory setting and conducted outside the UK. The purpose of this multicentre randomised controlled trial is to compare the effects of HIIT and MISS training in patients with CHD attending UK CR programmes. Methods and analysis This pragmatic study will randomly allocate 510 patients with CHD to 8 weeks of twice weekly HIIT or MISS training at 3 centres in the UK. HIIT will consist of 10 high-intensity (85–90% peak power output (PPO)) and 10 low-intensity (20–25% PPO) intervals, each lasting 1 min. MISS training will follow usual care recommendations, adhering to currently accepted UK guidelines (ie, >20 min continuous exercise at 40–70% heart rate reserve). Outcome measures will be assessed at baseline, 8 weeks and 12 months. The primary outcome for the trial will be change in VO2 peak as determined by maximal cardiopulmonary exercise testing. Secondary measures will assess physiological, psychosocial and economic outcomes. Ethics and dissemination The study protocol V.1.0, dated 1 February 2016, was approved by the NHS Health Research Authority, East Midlands—Leicester South Research Ethics Committee (16/EM/0079). Recruitment will start in August 2016 and will be completed in June 2018. Results will be published in peer-reviewed journals, presented at national and international scientific meetings and are expected to inform future national guidelines for exercise training in UK CR. Trial registration number NCT02784873; pre-results.

Randomised feasibility trial into the effects of low-frequency electrical muscle stimulation in advanced heart failure patients

Objectives Low-frequency electrical muscle stimulation (LF-EMS) may have the potential to reduce breathlessness and increase exercise capacity in the chronic heart failure population who struggle to adhere to conventional exercise. The study’s aim was to establish if a randomised controlled trial of LF-EMS was feasible. Design and setting Double blind (participants, outcome assessors), randomised study in a secondary care outpatient cardiac rehabilitation programme. Participants Patients with severe heart failure (New York Heart Association class III–IV) having left ventricular ejection fraction <40% documented by echocardiography were eligible. Interventions Participants were randomised (remotely by computer) to 8 weeks (5×60 mins per week) of either LF-EMS intervention (4 Hz, continuous, n=30) or sham placebo (skin level stimulation only, n=30) of the quadriceps and hamstrings muscles. Participants used the LF-EMS straps at home and were supervised weekly Outcome measures Recruitment, adherence and tolerability to the intervention were measured during the trial as well as physiological outcomes (primary outcome: 6 min walk, secondary outcomes: quadriceps strength, quality of life and physical activity). Results Sixty of 171 eligible participants (35.08%) were recruited to the trial. 12 (20%) of the 60 patients (4 LF-EMS and 8 sham) withdrew. Forty-one patients (68.3%), adhered to the protocol for at least 70% of the sessions. The physiological measures indicated no significant differences between groups in 6 min walk distance(p=0.13) and quality of life (p=0.55) although both outcomes improved more with LF-EMS. Conclusion Patients with severe heart failure can be recruited to and tolerate LF-EMS studies. A larger randomised controlled trial (RCT) in the advanced heart failure population is technically feasible, although adherence to follow-up would be challenging. The preliminary improvements in exercise capacity and quality of life were minimal and this should be considered if planning a larger trial. Trial registration number ISRCTN16749049