Mindfulness-based stress management: Findings from randomized controlled trials

The use of Mindfulness has become increasingly popular in the field of psychotherapy and counselling, and is now finding application in unexpected places. Is it just another therapeutic fad or an evidence-based intervention with lasting value? ROBERT KING provides a timely review of the research literature to provide a summary of the findings of randomised control trials of the clinical efficacy or effectiveness of Mindfulness as a stress reduction intervention.

A randomized trial of a telephone-delivered exercise intervention for non-urban dwelling women newly diagnosed with breast cancer : exercise for health

Physical activity is important following breast cancer. Trials of non-face-to-face interventions are needed to assist in reaching women living outside major metropolitan areas. This study seeks to evaluate the feasibility and effectiveness of a telephone-delivered, mixed aerobic and resistance exercise intervention for non-urban Australian women with breast cancer. A randomized controlled trial comparing an 8-month intervention delivered by exercise physiologists (n = 73) to usual care (n = 70). Sixty-one percent recruitment rate and 96% retention at 12 months; 79% of women in the intervention group received at least 75% of calls; odds (OR, 95% CI) of meeting intervention targets favored the intervention group for resistance training (OR 3.2; 1.2, 8.9) and aerobic (OR 2.1; 0.8, 5.5) activity. Given the limited availability of physical activity programs for non-urban women with breast cancer, results provide strong support for feasibility and modest support for the efficacy of telephone-delivered interventions.

The next generation health intervention tool - Can smart phone applications help young people track and moderate alcohol use and potential harms?

Whilst alcohol is a common feature of many social gatherings, there are numerous immediate and long-term health and social harms associated with its abuse. Alcohol consumption is the world’s third largest risk factor for disease and disability with almost 4% of all deaths worldwide attributed to alcohol. Not surprisingly, alcohol use and binge drinking by young people is of particular concern with Australian data reporting that 39% of young people (18-19yrs) admitted drinking at least weekly and 32% drank to levels that put them at risk of alcohol-related harm. The growing market penetration and connectivity of smartphones may be an opportunities for innovation in promoting health-related self-management of substance use. However, little is known about how best to harness and optimise this technology for health-related intervention and behaviour change. This paper explores the utility and interface of smartphone technology as a health intervention tool to monitor and moderate alcohol use. A review of the psychological health applications of this technology will be presented along with the findings of a series of focus groups, surveys and behavioural field trials of several drink-monitoring applications. Qualitative and quantitative data will be presented on the perceptions, preferences and utility of the design, usability and functionality of smartphone apps to monitoring and moderate alcohol use. How these findings have shaped the development and evolution of the OnTrack app will be specifically discussed, along with future directions and applications of this technology in health intervention, prevention and promotion.

A systematic review of baseline psychosocial characterisation in dietary randomised controlled trials for weight loss

BACKGROUND/OBJECTIVE: To investigate the extent of baseline psychosocial characterisation of subjects in published dietary randomised controlled trials (RCTs) for weight loss. SUBJECTS/METHODS: Systematic review of adequately sized (nX10) RCTs comprising X1 diet-alone arm for weight loss were included for this systematic review. More specifically, trials included overweight (body mass index 425 kg/m2) adults, were of duration X8 weeks and had body weight as the primary outcome. Exclusion criteria included specific psychological intervention (for example, Cognitive Behaviour Therapy (CBT)), use of web-based tools, use of supplements, liquid diets, replacement meals and very-low calorie diets. Physical activity intervention was restricted to general exercise only (not supervised or prescribed, for example, VO2 maximum level). RESULTS: Of 176 weight-loss RCTs published during 2008–2010, 15 met selection criteria and were assessed for reported psychological characterisation of subjects. All studies reported standard characterisation of clinical and biochemical characteristics of subjects. Eleven studies reported no psychological attributes of subjects (three of these did exclude those taking psychoactive medication). Three studies collected data on particular aspects of psychology related to specific research objectives (figure scale rating, satiety and quality-of-life). Only one study provided a comprehensive background on psychological attributes of subjects. CONCLUSION: Better characterisation in behaviour-change interventions will reduce potential confounding and enhance generalisability of such studies.

Depression scores predict adherence in a dietary weight loss intervention trial

Background & aims Depression has a complex association with cardiometabolic risk, both directly as an independent factor and indirectly through mediating effects on other risk factors such as BMI, diet, physical activity, and smoking. Since changes to many cardiometabolic risk factors involve behaviour change, the rise in depression prevalence as a major global health issue may present further challenges to long-term behaviour change to reduce such risk. This study investigated associations between depression scores and participation in a community-based weight management intervention trial. Methods A group of 64 overweight (BMI > 27), otherwise healthy adults, were recruited and randomised to follow either their usual diet, or an isocaloric diet in which saturated fat was replaced with monounsaturated fat (MUFA), to a target of 50% total fat, by adding macadamia nuts to the diet. Subjects were assessed for depressive symptoms at baseline and at ten weeks using the Beck Depression Inventory (BDI-II). Both control and intervention groups received advice on National Guidelines for Physical Activity and adhered to the same protocol for food diary completion and trial consultations. Anthropometric and clinical measurements (cholesterol, inflammatory mediators) also were taken at baseline and 10 weeks. Results During the recruitment phase, pre-existing diagnosed major depression was one of a range of reasons for initial exclusion of volunteers from the trial. Amongst enrolled participants, there was a significant correlation (R = −0.38, p < 0.05) between BDI-II scores at baseline and duration of participation in the trial. Subjects with a baseline BDI ≥10 (moderate to severe depression symptoms) were more likely to dropout of the trial before week 10 (p < 0.001). BDI-II scores in the intervention (MUFA) diet group decreased, but increased in the control group over the 10-week period. Univariate analysis of variance confirmed these observations (adjusted R2 = 0.257, p = 0.01). Body weight remained static over the 10-week period in the intervention group, corresponding to a relative increase in the control group (adjusted R2 = 0.097, p = 0.064). Conclusions Depression symptoms have the potential to affect enrolment in and adherence to dietbased risk reduction interventions, and may consequently influence the generalisability of such trials. Depression scores may therefore be useful for characterising, screening and allocating subjects to appropriate treatment pathways.

COX-derived prostanoid pathways in gastrointestinal cancer development and progression : novel targets for prevention and intervention

Arachidonic acid metabolism through cyclooxygenase (COX) pathways leads to the generation of biologically active eicosanoids. Eicosanoid expression levels vary during development and progression of gastrointestinal (GI) malignancies. COX-2 is the major COX-isoform responsible for G.I. cancer development/progression. COX-2 expression increases during progression from a normal to cancerous state. Evidence from observational studies has demonstrated that chronic NSAID use reduces the risk of cancer development, while both incidence and risk of death due to G.I. cancers were significantly reduced by daily aspirin intake. A number of randomized controlled trials (APC trial, Prevention of Sporadic Adenomatous Polyps trial, APPROVe trial) have also shown a significant protective effect in patients receiving selective COX-2 inhibitors. However, chronic use of selective COX-2 inhibitors at high doses was associated with increased cardiovascular risk, while NSAIDs have also been associated with increased risk. More recently, downstream effectors of COX-signaling have been investigated in cancer development/progression. PGE 2, which binds to both EP and PPAR receptors, is the major prostanoid implicated in the carcinogenesis of G.I. cancers. The role of TXA 2 in G.I. cancers has also been examined, although further studies are required to uncover its role in carcinogenesis. Other prostanoids investigated include PGD 2 and its metabolite 15d-PGJ2, PGF 1α and PGI 2. Targeting these prostanoids in G.I. cancers has the promise of avoiding cardiovascular toxicity associated with chronic selective COX-2 inhibition, while maintaining anti-tumor reactivity.A progressive sequence from normal to pre-malignant to a malignant state has been identified in G.I. cancers. In this review, we will discuss the role of the COX-derived prostanoids in G.I. cancer development and progression. Targeting these downstream prostanoids for chemoprevention and/or treatment of G.I. cancers will also be discussed. Finally, we will highlight the latest pre-clinical technologies as well as avenues for future investigation in this highly topical research field. © 2011 Elsevier B.V.

Prevention and treatment of acute radiation-induced skin reactions : a systematic review and meta-analysis of randomized controlled trials

Background Radiation-induced skin reaction (RISR) is a common side effect that affects the majority of cancer patients receiving radiation treatment. RISR is often characterised by swelling,redness, pigmentation, fibrosis, and ulceration, pain, warmth, burning, and itching of the skin. The aim of this systematic review was to assess the effects of interventions which aim to prevent or manage RISR in people with cancer. Methods We searched the following databases up to November 2012: Cochrane Skin Group Specialised Register, CENTRAL (2012, Issue 11), MEDLINE (from 1946), EMBASE (from 1974), PsycINFO (from 1806), CINAHL (from 1981) and LILACS (from 1982). Randomized controlled trials evaluating interventions for preventing or managing RISR in cancer patients were included. The primary outcomes were development of RISR, and levels of RISR and symptom severity. Secondary outcomes were time taken to develop erythema or dry desquamation; quality of life; time taken to heal, a number of skin reaction and symptom severity measures; cost, participant satisfaction; ease of use and adverse effects. Where appropriate, we pooled results of randomized controlled trials using mean differences (MD) or odd ratios (OR) with 95% confidence intervals (CI). Results Forty-seven studies were included in this review. These evaluated six types of interventions (oral systemic medications; skin care practices; steroidal topical therapies; non-steroidal topical therapies; dressings and other). Findings from two meta-analyses demonstrated significant benefits of oral Wobe-Mugos E for preventing RISR (OR 0.13 (95% CI 0.05 to 0.38)) and limiting the maximal level of RISR (MD −0.92 (95% CI −1.36 to −0.48)). Another meta-analysis reported that wearing deodorant does not influence the development of RISR (OR 0.80 (95% CI 0.47 to 1.37)). Conclusions Despite the high number of trials in this area, there is limited good, comparative research that provides definitive results suggesting the effectiveness of any single intervention for reducing RISR. More research is required to demonstrate the usefulness of a wide range of products that are being used for reducing RISR. Future efforts for reducing RISR severity should focus on promising interventions, such as Wobe-Mugos E and oral zinc.

The role of the arachidonic acid pathway in NSCLC development and progression : novel approaches for therapeutic intervention

Arachidonic acid metabolism through cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P-450 epoxygenase (EPOX) pathways is responsible for the formation of biologically active eicosanoids, including prostanoids, leukotrienes, hydroxyeicosatetraenoic acid, epoxyeicosatrienoic acid and hydroperoxyeicosatetraenoic acids. Altered eicosanoid expression levels are commonly observed during tumour development and progression of a range of malignancies, including non-small cell lung cancer (NSCLC). Arachidonic acid-derived eicosanoids affect a range of biological phenomena to modulate tumour processes such as cell growth, survival, angiogenesis, cell adhesion, invasion and migration and metastatic potential. Numerous studies have demonstrated that eicosanoids modulate NSCLC development and progression, while targeting these pathways has generally been shown to inhibit tumour growth/progression. Modulation of these arachidonic acid-derived pathways for the prevention and/or treatment of NSCLC has been the subject of significant interest over the past number of years, with a number of clinical trials examining the potential of COX and LOX inhibitors in combination with traditional and novel molecular approaches. However, results from these trials have been largely disappointing. Furthermore, enthusiasm for the use of selective COX-2 inhibitors for cancer prevention/treatment waned, due to their association with adverse cardiovascular events in chemoprevention trials. While COX and LOX targeting may both retain promise for NSCLC prevention and/or treatment, there is an urgent need to understand the downstream signalling mechanisms through which these and other arachidonic acid-derived signalling pathways mediate their effects on tumourigenesis. This will allow for development of safer and potentially more effective strategies for NSCLC prevention and/or treatment. Chemoprevention studies with PGI2 analogues have demonstrated considerable promise, while binding to/signalling through PGE2 receptors have also been the subject of interest for NSCLC treatment. In this chapter, the role of the eicosanoid signalling pathways in non-small cell lung cancer will be discussed. In particular, the effect of the eicosanoids on tumour cell proliferation, their roles in induction of cell death, effects on angiogenesis, migration, invasion and their regulation of the immune response will be assessed, with signal transduction pathways involved in these processes also discussed. Finally, novel approaches targeting these arachidonic acid-derived eicosanoids (using pharmacological or natural agents) for chemoprevention and/or treatment of NSCLC will be outlined. Elucidating the molecular mechanisms underlying the effects of specific or general arachidonic acid pathway modulators may lead to the design of biologically and pharmacologically targeted therapeutic strategies for NSCLC prevention/treatment, which may be used alone or in combination with conventional therapies.

Long-term azithromycin for Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease (Bronchiectasis Intervention Study) : a multicentre, double-blind, randomised controlled trial

Background Indigenous children in high-income countries have a heavy burden of bronchiectasis unrelated to cystic fibrosis. We aimed to establish whether long-term azithromycin reduced pulmonary exacerbations in Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease. Methods Between Nov 12, 2008, and Dec 23, 2010, we enrolled Indigenous Australian, Maori, and Pacific Island children aged 1—8 years with either bronchiectasis or chronic suppurative lung disease into a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial. Eligible children had had at least one pulmonary exacerbation in the previous 12 months. Children were randomised (1:1 ratio, by computer-generated sequence with permuted block design, stratified by study site and exacerbation frequency [1—2 vs ≥3 episodes in the preceding 12 months]) to receive either azithromycin (30 mg/kg) or placebo once a week for up to 24 months. Allocation concealment was achieved by double-sealed, opaque envelopes; participants, caregivers, and study personnel were masked to assignment until after data analysis. The primary outcome was exacerbation (respiratory episodes treated with antibiotics) rate. Analysis of the primary endpoint was by intention to treat. At enrolment and at their final clinic visits, children had deep nasal swabs collected, which we analysed for antibiotic-resistant bacteria. This study is registered with the Australian New Zealand Clinical Trials Registry; ACTRN12610000383066. Findings 45 children were assigned to azithromycin and 44 to placebo. The study was stopped early for feasibility reasons on Dec 31, 2011, thus children received the intervention for 12—24 months. The mean treatment duration was 20·7 months (SD 5·7), with a total of 902 child-months in the azithromycin group and 875 child-months in the placebo group. Compared with the placebo group, children receiving azithromycin had significantly lower exacerbation rates (incidence rate ratio 0·50; 95% CI 0·35—0·71; p<0·0001). However, children in the azithromycin group developed significantly higher carriage of azithromycin-resistant bacteria (19 of 41, 46%) than those receiving placebo (four of 37, 11%; p=0·002). The most common adverse events were non-pulmonary infections (71 of 112 events in the azithromycin group vs 132 of 209 events in the placebo group) and bronchiectasis-related events (episodes or investigations; 22 of 112 events in the azithromycin group vs 48 of 209 events in the placebo group); however, study drugs were well tolerated with no serious adverse events being attributed to the intervention. Interpretation Once-weekly azithromycin for up to 24 months decreased pulmonary exacerbations in Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease. However, this strategy was also accompanied by increased carriage of azithromycin-resistant bacteria, the clinical consequences of which are uncertain, and will need careful monitoring and further study.

Building resilience in transcultural adults (BRiTA) : developing a novel preventative intervention

There is a dearth of preventative programs that enhance the Australian culturally and linguistically diverse (CALD) adults’ resilience to cope with the acculturation process. This article introduces the reader to the BRiTA Futures for Adults and Parents, a culture and language sensitive program for the CALD. The conceptual framework and the development process are described. The manualised program consisting of one introductory and eight intervention modules is presented. A training program is also developed to train facilitators, who can deliver the program in English or other languages. Preliminary trials indicated that the program was received well by the consumers. A block mode, instead of the traditional weekly sessions, appeared to be more practical for the small population for which it was trialled. Implications and future directions are discussed.

Study protocol : a randomised controlled trial of a theory-based online intervention to improve sun safety among Australian adults

Background The effects of exposure to ultraviolet radiation are a significant concern in Australia which has one of the highest incidences of skin cancer in the world. Despite most skin cancers being preventable by encouraging consistent adoption of sun-protective behaviours, incidence rates are not decreasing. There is a dearth of research examining the factors involved in engaging in sun-protective behaviours. Further, online multi-behavioural theory-based interventions have yet to be explored fully as a medium for improving sun-protective behaviour in adults. This paper presents the study protocol of a randomised controlled trial of an online intervention based on the Theory of Planned Behaviour (TPB) that aims to improve sun safety among Australian adults. Methods/Design Approximately 420 adults aged 18 and over and predominantly from Queensland, Australia, will be recruited and randomised to the intervention (n = 200), information only (n = 200) or the control group (n = 20). The intervention focuses on encouraging supportive attitudes and beliefs toward sun-protective behaviour, fostering perceptions of normative support for sun protection, and increasing perceptions of control/self-efficacy over sun protection. The intervention will be delivered online over a single session. Data will be collected immediately prior to the intervention (Time 1), immediately following the intervention (Time 1b), and one week (Time 2) and one month (Time 3) post-intervention. Primary outcomes are intentions to sun protect and sun-protective behaviour. Secondary outcomes are the participants’ attitudes toward sun protection, perceptions of normative support for sun protection (i.e. subjective norms, group norms, personal norms and image norms) and perceptions of control/self-efficacy toward sun protection. Discussion The study will contribute to an understanding of the effectiveness of a TPB-based online intervention to improve Australian adults’ sun-protective behaviour. Trials registry Australian and New Zealand Trials Registry number ACTRN12613000470796

Breathe easier online : evaluation of a randomized controlled pilot trial of an internet-based intervention to improve well-being in children and adolescents with a chronic respiratory condition

Background Chronic respiratory illnesses are the most common group of childhood chronic health conditions and are overrepresented in socially isolated groups. Objective To conduct a randomized controlled pilot trial to evaluate the efficacy of Breathe Easier Online (BEO), an Internet-based problem-solving program with minimal facilitator involvement to improve psychosocial well-being in children and adolescents with a chronic respiratory condition. Methods We randomly assigned 42 socially isolated children and adolescents (18 males), aged between 10 and 17 years to either a BEO (final n = 19) or a wait-list control (final n = 20) condition. In total, 3 participants (2 from BEO and 1 from control) did not complete the intervention. Psychosocial well-being was operationalized through self-reported scores on depression symptoms and social problem solving. Secondary outcome measures included self-reported attitudes toward their illness and spirometry results. Paper-and-pencil questionnaires were completed at the hospital when participants attended a briefing session at baseline (time 1) and in their homes after the intervention for the BEO group or a matched 9-week time period for the wait-list group (time 2). Results The two groups were comparable at baseline across all demographic measures (all F < 1). For the primary outcome measures, there were no significant group differences on depression (P = .17) or social problem solving (P = .61). However, following the online intervention, those in the BEO group reported significantly lower depression (P = .04), less impulsive/careless problem solving (P = .01), and an improvement in positive attitude toward their illness (P = .04) compared with baseline. The wait-list group did not show these differences. Children in the BEO group and their parents rated the online modules very favorably. Conclusions Although there were no significant group differences on primary outcome measures, our pilot data provide tentative support for the feasibility (acceptability and user satisfaction) and initial efficacy of an Internet-based intervention for improving well-being in children and adolescents with a chronic respiratory condition. Trial registration Australian New Zealand Clinical Trials Registry number: ACTRN12610000214033;

Testing the effectiveness of a self-efficacy based exercise intervention for adults with venous leg ulcers : protocol of a randomised controlled trial

Background: Exercise and adequate self-management capacity may be important strategies in the management of venous leg ulcers. However, it remains unclear if exercise improves the healing rates of venous leg ulcers and if a self-management exercise program based on self-efficacy theory is well adhered to. Method/Design: This is a randomised controlled in adults with venous leg ulcers to determine the effectiveness of a self-efficacy based exercise intervention. Participants with venous leg ulcers are recruited from 3 clinical sites in Australia. After collection of baseline data, participants are randomised to either an intervention group or control group. The control group receive usual care, as recommended by evidence based guidelines. The intervention group receive an individualised program of calf muscle exercises and walking. The twelve week exercise program integrates multiple elements, including up to six telephone delivered behavioural coaching and goal setting sessions, supported by written materials, a pedometer and two follow-up booster calls if required. Participants are encouraged to seek social support among their friends, self-monitor their weekly steps and lower limb exercises. The control group are supported by a generic information sheet that the intervention group also receive encouraging lower limb exercises, a pedometer for self-management and phone calls at the same time points as the intervention group. The primary outcome is the healing rates of venous leg ulcers which are assessed at fortnightly clinic appointments. Secondary outcomes, assessed at baseline and 12 weeks: functional ability (range of ankle motion and Tinetti gait and balance score), quality of life and self-management scores. Discussion: This study seeks to address a significant gap in current wound management practice by providing evidence for the effectiveness of a home-based exercise program for adults with venous leg ulcers. Theory-driven, evidence-based strategies that can improve an individual’s exercise self-efficacy and self-management capacity could have a significant impact in improving the management of people with venous leg ulcers. Information gained from this study will provide much needed information on management of this chronic disease to promote health and independence in this population. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12612000475842 Trial status: Current follow up

Clinical trials in pediatrics

“Children are not little adults.” Almost all aspects of children's health including clinical trials and drug development are poor cousins of adult health. Over the years, pediatricians worldwide caution against blind extrapolation of adult data to children as it may result in considerable harm [1,2]. Also, it is increasingly recognized that the roots of many chronic diseases in adulthood stem from childhood and tackling health issues in children lead to improved health in adults [3,4]. Furthermore, investment in early childhood has long-term benefits in adults not only in health but also in other aspects of life such as education and crime reduction [4,5]. Arguably, health at birth is the single most important predictor of health in adulthood as the inequality of an infant at birth has intergenerational effects [5]. The Carolina Abecedarian Project showed that early childhood programs that are of high quality result in substantial societal benefits (e.g., reduction of crime, increased earnings, better education) [4,5]. A recent publication from this project found that this benefit also translated into improved adult health outcomes [4]. In a randomized trial, Campbell and colleagues described that disadvantaged children who were randomized to the intervention group (early education, health screenings and nutrition program) had significantly lower rates of metabolic syndrome, obesity and hypertension, when aged in their mid-30s, compared with the control group [4]...

Androgen-targeted therapy-induced epithelial mesenchymal plasticity and neuroendocrine transdifferentiation in prostate cancer : an opportunity for intervention

Androgens regulate biological pathways to promote proliferation, differentiation, and survival of benign and malignant prostate tissue. Androgen receptor (AR) targeted therapies exploit this dependence and are used in advanced prostate cancer to control disease progression. Contemporary treatment regimens involve sequential use of inhibitors of androgen synthesis or AR function. Although targeting the androgen axis has clear therapeutic benefit, its effectiveness is temporary, as prostate tumor cells adapt to survive and grow. The removal of androgens (androgen deprivation) has been shown to activate both epithelial-to-mesenchymal transition (EMT) and neuroendocrine transdifferentiation (NEtD) programs. EMT has established roles in promoting biological phenotypes associated with tumor progression (migration/invasion, tumor cell survival, cancer stem cell-like properties, resistance to radiation and chemotherapy) in multiple human cancer types. NEtD in prostate cancer is associated with resistance to therapy, visceral metastasis, and aggressive disease. Thus, activation of these programs via inhibition of the androgen axis provides a mechanism by which tumor cells can adapt to promote disease recurrence and progression. Brachyury, Axl, MEK, and Aurora kinase A are molecular drivers of these programs, and inhibitors are currently in clinical trials to determine therapeutic applications. Understanding tumor cell plasticity will be important in further defining the rational use of androgen-targeted therapies clinically and provides an opportunity for intervention to prolong survival of men with metastatic prostate cancer.