Self-monitoring of blood glucose versus self-monitoring of urine glucose in adults with newly diagnosed Type 2 diabetes receiving structured education: a cluster randomized controlled trial.

AIMS: To compare the effectiveness and acceptability of self-monitoring of blood glucose with self-monitoring of urine glucose in adults with newly diagnosed Type 2 diabetes. METHODS: We conducted a multi-site cluster randomized controlled trial with practice-level randomization. Participants attended a structured group education programme, which included a module on self-monitoring using blood glucose or urine glucose monitoring. HbA1c and other biomedical measures as well as psychosocial data were collected at 6, 12 and 18 months. A total of 292 participants with Type 2 diabetes were recruited from 75 practices. RESULTS: HbA1c levels were significantly lower at 18 months than at baseline in both the blood monitoring group [mean (se) -12 (2) mmol/mol; -1.1 (0.2) %] and the urine monitoring group [mean (se) -13 (2) mmol/mol; -1.2 (0.2)%], with no difference between groups [mean difference adjusted for cluster effect and baseline value = -1 mmol/mol (95% CI -3, 2); -0.1% (95% CI -0.3, 0.2)]. Similar improvements were observed for the other biomedical outcomes, with no differences between groups. Both groups showed improvements in total treatment satisfaction, generic well-being, and diabetes-specific well-being, and had a less threatening view of diabetes, with no differences between groups at 18 months. Approximately one in five participants in the urine monitoring arm switched to blood monitoring, while those in the blood monitoring arm rarely switched (18 vs 1% at 18 months; P < 0.001). CONCLUSIONS: Participants with newly diagnosed Type 2 diabetes who attended structured education showed similar improvements in HbA1c levels at 18 months, regardless of whether they were assigned to blood or urine self-monitoring.

Fructose-1, 6-diphosphate (FDP) as a novel antidote for yellow oleander-induced cardiac toxicity: a randomized controlled double blind study

BACKGROUND: Cardiac toxicity due to ingestion of oleander plant seeds in Sri Lanka and some other South Asian countries is very common. At present symptomatic oleander seed poisoning carries a mortality of 10% in Sri Lanka and treatment of yellow oleander poisoning is limited to gastric decontamination and atropine administration. The only proven effective antidote is digoxin antibodies but these are not available for routine use because of the high cost. The main objective of this study is to investigate the effectiveness of a new and inexpensive antidote for patients with life threatening arrhythmias due oleander poisoning. METHOD/DESIGN: We set up a randomised double blind clinical trial to assess the effectiveness of Fructose 1, 6 diphosphate (FDP) in acute yellow oleander poisoning patients admitted to the adult medical wards of a tertiary hospital in Sri Lanka. Patients will be initially resuscitated following the national guidelines and eligible patients will be randomised to receive either FDP or an equal amount of normal saline. The primary outcome measure for this study is the sustained reversion to sinus rhythm with a heart rate greater than 50/min within 2 hours of completion of FDP/placebo bolus. Secondary outcomes include death, reversal of hyperkalaemia on the 6, 12, 18 and 24 hour samples and maintenance of sinus rhythm on the holter monitor. Analysis will be on intention-to-treat. DISCUSSION: This trial will provide information on the effectiveness of FDP in yellow oleander poisoning. If FDP is effective in cardiac glycoside toxicity, it would provide substantial benefit to the patients in rural Asia. The drug is inexpensive and thus could be made available at primary care hospitals if proven to be effective. TRIAL REGISTRATION: Current Controlled trial ISRCTN71018309.

Web-based alcohol intervention for Māori university students: double-blind, multi-site randomized controlled trial

AIMS: Like many indigenous peoples, New Zealand Māori bear a heavy burden of alcohol-related harm relative to their non-indigenous compatriots, and disparities are greatest among young adults. We tested the effectiveness of web-based alcohol screening and brief intervention (e-SBI) for reducing hazardous drinking among Māori university students. DESIGN: Parallel, double-blind, multi-site, randomized controlled trial. SETTING: Seven of New Zealand's eight universities. PARTICIPANTS: In April 2010, we sent e-mail invitations to all 6697 17-24-year-old Māori students to complete a brief web questionnaire including the Alcohol Use Disorders Identification Test (AUDIT)-C, a screening tool for hazardous and harmful drinking. Those screening positive were computer randomized to: <10 minutes of web-based alcohol assessment and personalized feedback (intervention) or screening alone (control). MEASUREMENTS: We conducted a fully automated 5-month follow-up assessment with observers and participants blinded to study hypotheses, design and intervention delivery. Pre-determined primary outcomes were: (i) frequency of drinking, (ii) amount consumed per typical drinking occasion, (iii) overall volume of alcohol consumed and (iv) academic problems. FINDINGS: Of the participants, 1789 were hazardous or harmful drinkers (AUDIT-C ≥ 4) and were randomized: 850 to control, 939 to intervention. Follow-up assessments were completed by 682 controls (80%) and 733 intervention group members (78%). Relative to controls, participants receiving intervention drank less often [RR = 0.89; 95% confidence interval (CI): 0.82-0.97], less per drinking occasion (RR = 0.92; 95% CI: 0.84-1.00), less overall (RR = 0.78; 95% CI: 0.69-0.89) and had fewer academic problems (RR = 0.81; 95% CI: 0.69-0.95). CONCLUSIONS: Web-based screening and brief intervention reduced hazardous and harmful drinking among non-help-seeking Māori students in a large-scale pragmatic trial. The study has wider implications for behavioural intervention in the important but neglected area of indigenous health.

Health coaching to prevent excessive gestational weight gain: a randomized-controlled trial

OBJECTIVES: The objectives of this study were to evaluate the efficacy of a health coaching (HC) intervention designed to prevent excessive gestational weight gain (GWG), and promote positive psychosocial and motivational outcomes in comparison with an Education Alone (EA) group. DESIGN: Randomized-controlled trial. METHODS: Two hundred and sixty-one women who were <18 weeks pregnant consented to take part. Those allocated to the HC group received a tailored HC intervention delivered by a Health Coach, whilst those in the EA group attended two education sessions. Women completed measures, including motivation, psychosocial variables, sleep quality, and knowledge, beliefs and expectations concerning GWG, at 15 weeks of gestation (Time 1) and 33 weeks of gestation (Time 2). Post-birth data were also collected at 2 months post-partum (Time 3). RESULTS: There was no intervention effect in relation to weight gained during pregnancy, rate of excessive GWG or birth outcomes. The only differences between HC and EA women were higher readiness (b = 0.29, 95% CIs = 0.03-0.55, p < .05) and the importance to achieve a healthy GWG (b = 0.27, 95% CIs = 0.02-0.52, p < .05), improved sleep quality (b = -0.22, 95% CIs = -0.44 to -0.03, p < .05), and increased knowledge for an appropriate amount of GWG that would be best for their baby's health (b = -1.75, 95% CI = -3.26 to -0.24, p < .05) reported by the HC at Time 2. CONCLUSIONS: Whilst the HC intervention was not successful in preventing excessive GWG, several implications for the design of future GWG interventions were identified, including the burden of the intervention commitment and the use of weight monitoring. Statement of contribution What is already known on the subject? Designing interventions to address gestational weight gain (GWG) continues to be a challenge. To date, health behaviour change factors have not been the focus of GWG interventions. What does this study add? Our health coaching (HC) intervention did not reduce GWG more so than education alone (EA). There was an intervention effect on readiness and importance to achieve healthy GWG. Yet there were no group differences regarding confidence to achieve healthy GWG post-intervention.

Effect of increasing dietary calcium through supplements and dairy food on body weight and body composition: a meta-analysis of randomised controlled trials

This meta-analysis of randomised controlled trials assessed the effect of Ca on body weight and body composition through supplementation or increasing dairy food intake. Forty-one studies met the inclusion criteria (including fifty-one trial arms; thirty-one with dairy foods (n 2091), twenty with Ca supplements (n 2711). Ca intake was approximately 900 mg/d higher in the supplement groups compared with control. In the dairy group, Ca intake was approximately 1300 mg/d. Ca supplementation did not significantly affect body weight (mean change ( - 0·17, 95 % CI - 0·70, 0·37) kg) or body fat (mean change ( - 0·19, 95 % CI - 0·51, 0·13) kg) compared to control. Similarly, increased dairy food intake did not affect body weight ( - 0·06, 95 % CI - 0·54, 0·43) kg or body fat change ( - 0·36, 95 % CI - 0·80, 0·09) kg compared to control. Sub-analyses revealed that dairy supplementation resulted in no change in body weight (nineteen studies, n 1010) ( - 0·32, 95 % CI - 0·93, 0·30 kg, P= 0·31), but a greater reduction in body fat (thirteen studies, n 564) ( - 0·96, 95 % CI - 1·46, - 0·46 kg, P < 0·001) in the presence of energy restriction over a mean of 4 months compared to control. Increasing dietary Ca intake by 900 mg/d as supplements or increasing dairy intake to approximately 3 servings daily (approximately 1300 mg of Ca/d) is not an effective weight reduction strategy in adults. There is, however, an indication that approximately 3 servings of dairy may facilitate fat loss on weight reduction diets in the short term.

Adoption and maintenance of gym-based strength training in the community setting in adults with excess weight or type 2 diabetes: a randomized controlled trial

BACKGROUND: Participant adoption and maintenance is a major challenge in strength training (ST) programs in the community-setting. In adults who were overweight or with type 2 diabetes (T2DM), the aim of this study was to compare the effectiveness of a standard ST program (SST) to an enhanced program (EST) on the adoption and maintenance of ST and cardio-metabolic risk factors and muscle strength. METHODS: A 12-month cluster-randomized controlled trial consisting of a 6-month adoption phase followed by a 6-month maintenance phase. In 2008-2009, men and women aged 40-75 years (n = 318) with T2DM (n = 117) or a BMI >25 (n = 201) who had not participated in ST previously were randomized into either a SST or an EST program (which included additional motivationally-tailored behavioral counselling). Adoption and maintenance were defined as undertaking ≥ 3 weekly gym-based exercise sessions during the first 6-months and from 6-12 months respectively and were assessed using a modified version of the CHAMPS (Community Healthy Activity Models Program for Seniors) instrument. RESULTS: Relative to the SST group, the adjusted odds ratio (OR) of adopting ST for all participants in the EST group was 3.3 (95 % CI 1.2 to 9.4). In stratified analyses including only those with T2DM, relative to the SST group, the adjusted OR of adopting ST in the EST group was 8.2 (95 % CI 1.5-45.5). No significant between-group differences were observed for maintenance of ST in either pooled or stratified analyses. In those with T2DM, there was a significant reduction in HbA1c in the EST compared to SST group during the adoption phase (net difference, -0.13 % [-0.26 to -0.01]), which persisted after 12-months (-0.17 % [-0.3 to -0.05]). CONCLUSIONS: A behaviorally-focused community-based EST intervention was more effective than a SST program for the adoption of ST in adults with excess weight or T2DM and led to greater improvements in glycemic control in those with T2DM. TRIAL REGISTRATION: Registered at ACTRN12611000695909 (Date registered 7/7/2011).

A pilot, multisite, randomized controlled trial of a self-directed coping skills training intervention for couples facing prostate cancer : accrual, retention, and data collection issues

PURPOSE: To examine the acceptability of the methods used to evaluate Coping-Together, one of the first self-directed coping skill intervention for couples facing cancer, and to collect preliminary efficacy data. METHODS: Forty-two couples, randomized to a minimal ethical care (MEC) condition or to Coping-Together, completed a survey at baseline and 2 months after, a cost diary, and a process evaluation phone interview. RESULTS: One hundred seventy patients were referred to the study. However, 57 couples did not meet all eligibility criteria, and 51 refused study participation. On average, two to three couples were randomized per month, and on average it took 26 days to enrol a couple in the study. Two couples withdrew from MEC, none from Coping-Together. Only 44 % of the cost diaries were completed, and 55 % of patients and 60 % of partners found the surveys too long, and this despite the follow-up survey being five pages shorter than the baseline one. Trends in favor of Coping-Together were noted for both patients and their partners. CONCLUSIONS: This study identified the challenges of conducting dyadic research, and a number of suggestions were put forward for future studies, including to question whether distress screening was necessary and what kind of control group might be more appropriate in future studies.

Multicenter randomized controlled trial of a home walking intervention after outpatient cardiac rehabilitation on health-related quality of life in women

BACKGROUND: Poor health-related quality of life (HRQL) has been shown to be predictive of adverse outcomes in cardiac patients. As women with coronary heart disease have been shown to have lower HRQL than men with coronary heart disease, women are at greater risk of a poor clinical outcome. This study tested the effect of a 12-week home walking intervention after completion of outpatient cardiac rehabilitation (OCR) on HRQL and maintenance of physical activity among women. DESIGN: Multicenter two-group randomized trial. METHODS: After completion of OCR, participants were randomly allocated to the intervention or usual care groups. The outcomes were HRQL (assessed using the MacNew Heart Disease HRQL instrument) and self-reported physical activity (assessed using the Stages of Change model of exercise behavior) at 3, 6, and 12 months after OCR. RESULTS: Seventy-two women were randomized to the intervention and 81 to usual care. Attrition was greater in the treatment group (13 vs. 1%). HRQL scores increased relative to the base level in both arms and were significantly higher in the intervention group at 6 months, but not at 3 or 12 months. Maintenance of physical activity declined over time in both groups, however, this decline was significantly reduced among women in the intervention group. CONCLUSION: HRQL improved in both groups, but seemed to increase earlier among women in the intervention group. As maintenance of physical activity was higher among women in the intervention group, this minimal intervention could be used to facilitate women's progression from supervised to independent exercise.

Randomized controlled trial of proactive web-based alcohol screening and brief intervention for university students

BACKGROUND: University students drink more heavily than their nonstudent peers and are often unaware that their drinking is risky and exceeds normative levels. We tested the efficacy of a proactive Web-based alcohol screening and brief intervention program. METHODS: A randomized controlled trial was conducted at an Australian university in 2007. Invitations were sent to 13 000 undergraduates (age range, 17-24 years) to complete a Web-based Alcohol Use Disorders Identification Test. Of 7237 students who responded, 2435 scored in the hazardous/harmful range (> or =8) and were randomized, and 2050 (84%) completed at least 1 follow-up assessment. Intervention was 10 minutes of Web-based motivational assessment and personalized feedback. Controls received only screening. Follow-up assessments were conducted at 1 and 6 months with observers and participants blinded to allocation. Outcome measures were drinking frequency, typical occasion quantity, overall volume, number of personal problems, an academic problems score, prevalence of binge drinking, and prevalence of heavy drinking. RESULTS: Mean (SD) baseline Alcohol Use Disorders Identification Test scores for control and intervention groups were 14.3 (5.1) and 14.2 (5.1), respectively. After 1 month, participants receiving intervention drank less often (rate ratio [RR], 0.89; 95% confidence interval [CI], 0.83-0.94), smaller quantities per occasion (RR, 0.93; 95% CI, 0.88-0.98), and less alcohol overall (RR, 0.83; 95% CI, 0.78-0.90) than did controls. Differences in alcohol-related harms were nonsignificant. At 6 months, intervention effects persisted for drinking frequency (RR, 0.91; 95% CI, 0.85-0.97) and overall volume (RR, 0.89; 95% CI, 0.82-0.96) but not for other variables. CONCLUSION: Proactive Web-based screening and intervention reduces drinking in undergraduates, and such a program could be implemented widely.

A web- and mobile phone-based intervention to prevent obesity in 4-year-olds (MINISTOP): a population-based randomized controlled trial

BACKGROUND: Childhood obesity is an increasing health problem globally. Overweight and obesity may be established as early as 2-5 years of age, highlighting the need for evidence-based effective prevention and treatment programs early in life. In adults, mobile phone based interventions for weight management (mHealth) have demonstrated positive effects on body mass, however, their use in child populations has yet to be examined. The aim of this paper is to report the study design and methodology of the MINSTOP (Mobile-based Intervention Intended to Stop Obesity in Preschoolers) trial.

METHODS/DESIGN: A two-arm, parallel design randomized controlled trial in 300 healthy Swedish 4-year-olds is conducted. After baseline measures, parents are allocated to either an intervention- or control group. The 6- month mHealth intervention consists of a web-based application (the MINSTOP app) to help parents promote healthy eating and physical activity in children. MINISTOP is based on the Social Cognitive Theory and involves the delivery of a comprehensive, personalized program of information and text messages based on existing guidelines for a healthy diet and active lifestyle in pre-school children. Parents also register physical activity and intakes of candy, soft drinks, vegetables as well as fruits of their child and receive feedback through the application. Primary outcomes include body fatness and energy intake, while secondary outcomes are time spent in sedentary, moderate, and vigorous physical activity, physical fitness and intakes of fruits and vegetables, snacks, soft drinks and candy. Food and energy intake (Tool for Energy balance in Children, TECH), body fatness (pediatric option for BodPod), physical activity (Actigraph wGT3x-BT) and physical fitness (the PREFIT battery of five fitness tests) are measured at baseline, after the intervention (six months after baseline) and at follow-up (12 months after baseline).

DISCUSSION: This novel study will evaluate the effectiveness of a mHealth program for mitigating gain in body fatness among 4-year-old children. If the intervention proves effective it has great potential to be implemented in child-health care to counteract childhood overweight and obesity.

The use of mixed methods in drug discovery: integrating qualitative methods into clinical trials

Contemporary methods in clinical trials are pivoted around hypothesis confirmation, not generation. This is a problem for new drug discovery, since the pharmacokinetic or receptor profile of most novel agents do not link to pathophysiology, which is very poorly understood. Therefore, it is difficult to impute the therapeutic potential of a candidate agent. Most psychotropic agents were discovered serendipitously, either through careful clinical observation or by researchers finding unexpected associations in datasets. Methods that increase the ability to detect latent signals in data are needed. These include mixed methods that incorporate qualitative methods into randomized controlled trials.

This chapter proposes a methodology for the integration of mixed methods in clinical trials, fusing qualitative and quantitative methods, and presents an exemplar using this approach.

Mixed methods show potential for signal detection, hypothesis generation, and associations that may be otherwise undetected in traditional clinical trials.

Ascorbic acid supplementation improves skeletal muscle oxidative stress and insulin sensitivity in people with type 2 diabetes: findings of a randomized controlled study

AIM/HYPOTHESIS: Skeletal muscle insulin resistance and oxidative stress are characteristic metabolic disturbances in people with type 2 diabetes. Studies in insulin resistant rodents show an improvement in skeletal muscle insulin sensitivity and oxidative stress following antioxidant supplementation. We therefore investigated the potential ameliorative effects of antioxidant ascorbic acid (AA) supplementation on skeletal muscle insulin sensitivity and oxidative stress in people with type 2 diabetes. METHODS: Participants with stable glucose control commenced a randomized cross-over study involving four months of AA (2×500mg/day) or placebo supplementation. Insulin sensitivity was assessed using a hyperinsulinaemic, euglycaemic clamp coupled with infusion of 6,6-D2 glucose. Muscle biopsies were measured for AA concentration and oxidative stress markers that included basal measures (2',7'-dichlorofluorescin [DCFH] oxidation, ratio of reduced-to-oxidized glutathione [GSH/GSSG] and F2-Isoprostanes) and insulin-stimulated measures (DCFH oxidation). Antioxidant concentrations, citrate synthase activity and protein abundances of sodium-dependent vitamin C transporter 2 (SVCT2), total Akt and phosphorylated Akt (ser473) were also measured in muscle samples. RESULTS: AA supplementation significantly increased insulin-mediated glucose disposal (delta rate of glucose disappearance; ∆Rd) (p=0.009), peripheral insulin-sensitivity index (p=0.046), skeletal muscle AA concentration (p=0.017) and muscle SVCT2 protein expression (p=0.008); but significantly decreased skeletal muscle DCFH oxidation during hyperinsulinaemia (p=0.007) when compared with placebo. Total superoxide dismutase activity was also lower following AA supplementation when compared with placebo (p=0.006). Basal oxidative stress markers, citrate synthase activity, endogenous glucose production, HbA1C and muscle Akt expression were not significantly altered by AA supplementation. CONCLUSIONS/INTERPRETATION: In summary, oral AA supplementation ameliorates skeletal muscle oxidative stress during hyperinsulinaemia and improves insulin-mediated glucose disposal in people with type 2 diabetes. Findings implicate AA supplementation as a potentially inexpensive, convenient, and effective adjunct therapy in the treatment of insulin resistance in people with type 2 diabetes.

The extended Infant Feeding, Activity and Nutrition Trial (InFANT Extend) Program : a cluster-randomized controlled trial of an early intervention to prevent childhood obesity

BACKGROUND: Understanding how we can prevent childhood obesity in scalable and sustainable ways is imperative. Early RCT interventions focused on the first two years of life have shown promise however, differences in Body Mass Index between intervention and control groups diminish once the interventions cease. Innovative and cost-effective strategies seeking to continue to support parents to engender appropriate energy balance behaviours in young children need to be explored. METHODS/DESIGN: The Infant Feeding Activity and Nutrition Trial (InFANT) Extend Program builds on the early outcomes of the Melbourne InFANT Program. This cluster randomized controlled trial will test the efficacy of an extended (33 versus 15 month) and enhanced (use of web-based materials, and Facebook® engagement), version of the original Melbourne InFANT Program intervention in a new cohort. Outcomes at 36 months of age will be compared against the control group. DISCUSSION: This trial will provide important information regarding capacity and opportunities to maximize early childhood intervention effectiveness over the first three years of life. This study continues to build the evidence base regarding the design of cost-effective, scalable interventions to promote protective energy balance behaviors in early childhood, and in turn, promote improved child weight and health across the life course. TRIAL REGISTRATION: ACTRN12611000386932 . Registered 13 April 2011.

A process evaluation of the Supermarket Healthy Eating for Life (SHELf) randomized controlled trial

BACKGROUND: Supermarket Healthy Eating for Life (SHELf) was a randomized controlled trial that operationalized a socioecological approach to population-level dietary behaviour change in a real-world supermarket setting. SHELf tested the impact of individual (skill-building), environmental (20 % price reductions), and combined (skill-building + 20 % price reductions) interventions on women's purchasing and consumption of fruits, vegetables, low-calorie carbonated beverages and water. This process evaluation investigated the reach, effectiveness, implementation, and maintenance of the SHELf interventions.

METHODS: RE-AIM provided a conceptual framework to examine the processes underlying the impact of the interventions using data from participant surveys and objective sales data collected at baseline, post-intervention (3 months) and 6-months post-intervention. Fisher's exact, χ (2) and t-tests assessed differences in quantitative survey responses among groups. Adjusted linear regression examined the impact of self-reported intervention dose on food purchasing and consumption outcomes. Thematic analysis identified key themes within qualitative survey responses.

RESULTS: Reach of the SHELf interventions to disadvantaged groups, and beyond study participants themselves, was moderate. Just over one-third of intervention participants indicated that the interventions were effective in changing the way they bought, cooked or consumed food (p < 0.001 compared to control), with no differences among intervention groups. Improvements in purchasing and consumption outcomes were greatest among those who received a higher intervention dose. Most notably, participants who said they accessed price reductions on fruits and vegetables purchased (519 g/week) and consumed (0.5 servings/day) more vegetables. The majority of participants said they accessed (82 %) and appreciated discounts on fruits and vegetables, while there was limited use (40 %) and appreciation of discounts on low-calorie carbonated beverages and water. Overall reported satisfaction with, use, and impact of the skill-building resources was moderate. Maintenance of newly acquired behaviours was limited, with less than half of participants making changes or using study-provided resources during the 6-month post-intervention period.

CONCLUSIONS: SHELf's reach and perceived effectiveness were moderate. The interventions were more effective among those reporting greater engagement with them (an implementation-related construct). Maintenance of newly acquired behaviours proved challenging.