Treatment rationale study design for the MetLung trial : a randomized, double-blind phase III study of onartuzumab (MetMAb) in combination with erlotinib versus erlotinib alone in patients who have received standard chemotherapy for stage IIIB or IV met-positive non-small-cell lung cancer

We present the treatment rationale and study design of the MetLung phase III study. This study will investigate onartuzumab (MetMAb) in combination with erlotinib compared with erlotinib alone, as second- or third-line treatment, in patients with advanced non-small-cell lung cancer (NSCLC) who are Met-positive by immunohistochemistry. Approximately 490 patients (245 per treatment arm) will receive erlotinib (150 mg oral daily) plus onartuzumab or placebo (15 mg/kg intravenous every 3 weeks) until disease progression, unacceptable toxicity, patient or physician decision to discontinue, or death. The efficacy objectives of this study are to compare overall survival (OS) (primary endpoint), progression-free survival, and response rates between the 2 treatment arms. In addition, safety, quality of life, pharmacokinetics, and translational research will be investigated across treatment arms. If the primary objective (OS) is achieved, this study will provide robust results toward an alternative treatment option for patients with Met-positive second- or third-line NSCLC. © 2012 Elsevier Inc. All Rights Reserved.

Theory-based self-management programs for promoting recovery in community-dwelling stroke survivors : a systematic review

Background Post-stroke recovery is demanding. Increasing studies have examined the effectiveness of self-management programs for stroke survivors. However no systematic review has been conducted to summarize the effectiveness of theory-based stroke self-management programs. Objectives The aim is to present the best available research evidence about effectiveness of theory-based self-management programs on community-dwelling stroke survivors’ recovery. Inclusion criteria Types of participants All community-residing adults aged 18 years or above, and had a clinical diagnosis of stroke. Types of interventions Studies which examined effectiveness of a self-management program underpinned by a theoretical or conceptual framework for community-dwelling stroke survivors. Types of studies Randomized controlled trials. Types of outcomes Primary outcomes included health-related quality of life and self-management behaviors. Secondary outcomes included physical (activities of daily living), psychological (self-efficacy, depressive symptoms), and social outcomes (community reintegration, perceived social support). Search Strategy A three-step approach was adopted to identify all relevant published and unpublished studies in English or Chinese. Methodological quality The methodological quality of the included studies was assessed using the Joanna Briggs Institute critical appraisal checklist for experimental studies. Data Collection A standardized JBI data extraction form was used. There was no disagreement between the two reviewers on the data extraction results. Data Synthesis There were incomplete details about the number of participants and the results in two studies, which makes it impossible to perform meta-analysis. A narrative summary of the effectiveness of stroke self-management programs is presented. Results Three studies were included. The key issues of concern in methodological quality included insufficient information about random assignment, allocation concealment, reliability and validity of the measuring instruments, absence of intention-to-treat analysis, and small sample sizes. The three programs were designed based on the Stanford Chronic Disease Self-management program and were underpinned by the principles of self-efficacy. One study showed improvement in the intervention group in family and social roles three months after program completion, and work productivity at six months as measured by the Stroke Specific Quality of Life Scale (SSQOL). The intervention group also had an increased mean self-efficacy score in communicating with physicians six months after program completion. The mean changes from baseline in these variables were significantly different from the control group. No significant difference was found in time spent in aerobic exercise between the intervention and control groups at three and six months after program completion. Another study, using SSQOL, showed a significant interaction effect by treatment and time on family roles, fine motor tasks, self-care, and work productivity. However there was no significant interaction by treatment and time on self-efficacy. The third study showed improvement in quality of life, community participation, and depressive symptoms among the participants receiving the stroke self-management program, Stanford Chronic Disease Self-management program, or usual care six months after program completion. However, there was no significant difference between the groups. Conclusions There is inconclusive evidence about the effectiveness of theory-based stroke self-management programs on community-dwelling stroke survivors’ recovery. However the preliminary evidence suggests potential benefits in improving stroke survivors’ quality of life and self-efficacy.

Applying the ecological model of behavior change to a physical activity trial in retirement communities : description of the study protocol

Objectives To describe the intervention protocol for the first multilevel ecological intervention for physical activity in retirement communities that addresses individual, interpersonal and community influences on behavior change. Design A cluster randomized controlled trial design was employed with two study arms: a physical activity intervention and an attention control successful aging condition. Setting Sixteen continuing care retirement communities in San Diego County. Participants Three hundred twenty older adults, aged 65 years and older, are being recruited to participate in the trial. In addition, peer leaders are being recruited to lead some study activities, especially to sustain the intervention after study activities ceased. Intervention Participants in the physical activity trial receive individual, interpersonal and community intervention components. The individual level components include pedometers, goal setting and individual phone counseling. The interpersonal level components include group education sessions and peer-led activities. The community level components include resource audits and enumeration, tailored walking maps, and community improvement projects. The successful aging group receives individual and group attention about successful aging topics. Measurements The main outcome is light to moderate physical activity, measured objectively by accelerometry. Other objective outcomes included physical functioning, blood pressure, physical fitness, and cognitive functioning. Self report measures include depressive symptoms and health related quality of life. Results The intervention is being delivered successfully in the communities and compliance rates are high. Conclusion Ecological Models call for interventions that address multiple levels of the model. Previous studies have not included components at each level and retirement communities provide a model environment to demonstrate how to implement such an intervention.

A shared reading intervention with parents to enhance young children’s early literacy skills

Parental reading to children from an early age has been shown to enhance children’s emergent literacy skills. A pragmatic randomized controlled trial (RCT) was used to investigate the effects of two forms of shared reading interventions on children’s language and literacy skills. Parents of 80 preparatory year children from outer suburban schools of an Australian metropolitan city were trained to use shared reading strategies in an eight-week home intervention. Families were assigned to one of three groups: Dialogic Reading (DR), Dialogic Reading with the addition of Print Referencing (DR + PR), or an attention-matched control group. The sample comprised 42 boys and 38 girls ranging in age from 4.9 years to 6.3 years (M = 5.5, SD = 0.3). Data were collected at pre, post, and at three months follow-up. Measures assessed children’s oral language (receptive and expressive vocabulary), phonological awareness (rhyme, word completion), alphabet knowledge, and concepts about print. Analyses of change from pre to post showed significant effects for the DR and DR + PR groups compared to the control group on three of the six measures: expressive language, rhyme, and concepts about print. At 3-month follow-up assessment, the two intervention groups maintained significantly better performance on the measure of concepts of print only. At both time points, there were no group differences between the DR and DR+PR conditions. These findings illustrate the potential of a brief home focused intervention on promoting children’s emergent literacy.

Non-response bias in randomized control experiments in criminology : putting the Queensland Community Engagement Trial (QCET) under a microscope

Objectives The goal of this article is to examine whether or not the results of the Queensland Community Engagement Trial (QCET)-a randomized controlled trial that tested the impact of procedural justice policing on citizen attitudes toward police-were affected by different types of nonresponse bias. Method We use two methods (Cochrane and Elffers methods) to explore nonresponse bias: First, we assess the impact of the low response rate by examining the effects of nonresponse group differences between the experimental and control conditions and pooled variance under different scenarios. Second, we assess the degree to which item response rates are influenced by the control and experimental conditions. Results Our analysis of the QCET data suggests that our substantive findings are not influenced by the low response rate in the trial. The results are robust even under extreme conditions, and statistical significance of the results would only be compromised in cases where the pooled variance was much larger for the nonresponse group and the difference between experimental and control conditions was greatly diminished. We also find that there were no biases in the item response rates across the experimental and control conditions. Conclusion RCTs that involve field survey responses-like QCET-are potentially compromised by low response rates and how item response rates might be influenced by the control or experimental conditions. Our results show that the QCET results were not sensitive to the overall low response rate across the experimental and control conditions and the item response rates were not significantly different across the experimental and control groups. Overall, our analysis suggests that the results of QCET are robust and any biases in the survey responses do not significantly influence the main experimental findings.

Is age a factor in the success or failure of remote monitoring in heart failure? Telemonitoring and structured telephone support in elderly heart failure patients

Background There are few data regarding the effectiveness of remote monitoring for older people with heart failure. We conducted a post-hoc sub-analysis of a previously published large Cochrane systematic review and meta-analysis of relevant randomized controlled trials to determine whether structured telephone support and telemonitoring were effective in this population. Methods A post hoc sub-analysis of a systematic review and meta-analysis that applied the Cochrane methodology was conducted. Meta-analyses of all-cause mortality, all-cause hospitalizations and heart failure-related hospitalizations were performed for studies where the mean or median age of participants was 70 or more years. Results The mean or median age of participants was 70 or more years in eight of the 16 (n=2,659/5,613; 47%) structured telephone support studies and four of the 11 (n=894/2,710; 33%) telemonitoring studies. Structured telephone support (RR 0.80; 95% CI=0.63-1.00) and telemonitoring (RR 0.56; 95% CI=0.41-0.76) interventions reduced mortality. Structured telephone support interventions reduced heart failure-related hospitalizations (RR 0.81; 95% CI=0.67-0.99). Conclusion Despite a systematic bias towards recruitment of individuals younger than the epidemiological average into the randomized controlled trials, older people with heart failure did benefit from structured telephone support and telemonitoring. These post-hoc sub-analysis results were similar to overall effects observed in the main meta-analysis. While further research is required to confirm these observational findings, the evidence at hand indicates that discrimination by age alone may be not be appropriate when inviting participation in a remote monitoring service for heart failure.

A systematic review and meta-analysis : tailoring asthma treatment on eosinophilic markers (exhaled nitric oxide or sputum eosinophils)

Asthma severity and control can be measured both subjectively and objectively. Traditionally asthma treatments have been individualised using symptoms and spirometry/peak flow. Increasingly treatment tailored in accordance with inflammatory markers (sputum eosinophil counts or fractional exhaled nitric oxide (FeNO) data) is advocated as an alternative strategy. The objective of this review was to evaluate the efficacy of tailoring asthma interventions based on inflammatory markers (sputum analysis and FeNO) in comparison with clinical symptoms (with or without spirometry/peak flow) for asthma-related outcomes in children and adults. Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and reference lists of articles were searched. The last searches were in February 2009. All randomised controlled comparisons of adjustment of asthma treatment based on sputum analysis or FeNO compared with traditional methods (primarily clinical symptoms and spirometry/peak flow) were selected. Results of searches were reviewed against predetermined criteria for inclusion. Relevant studies were selected, assessed and data extracted independently by at least two people. The trial authors were contacted for further information. Data were analysed as 'intervention received' and sensitivity analyses performed. Six (2 adults and 4 children/adolescent) studies utilising FeNO and three adult studies utilising sputum eosinophils were included. These studies had a degree of clinical heterogeneity including definition of asthma exacerbations, duration of study and variations in cut-off levels for percentage of sputum eosinophils and FeNO to alter management in each study. Adults who had treatment adjusted according to sputum eosinophils had a reduced number of exacerbations compared with the control group (52 vs. 77 patients with >=1 exacerbation in the study period; p=0.0006). There was no significant difference in exacerbations between groups for FeNO compared with controls. The daily dose of inhaled corticosteroids at the end of the study was decreased in adults whose treatment was based on FeNO in comparison with the control group (mean difference -450.03 mug, 95% CI -676.73 to -223.34; p<0.0001). However, children who had treatment adjusted according to FeNO had an increase in their mean daily dose of inhaled corticosteroids (mean difference 140.18 mug, 95% CI 28.94 to 251.42; p=0.014). It was concluded that tailoring of asthma treatment based on sputum eosinophils is effective in decreasing asthma exacerbations. However, tailoring of asthma treatment based on FeNO levels has not been shown to be effective in improving asthma outcomes in children and adults. At present, there is insufficient justification to advocate the routine use of either sputum analysis (due to technical expertise required) or FeNO in everyday clinical practice.

Randomized trial of a clinic-based, community-supported, lifestyle intervention to improve physical activity and diet : The North Carolina enhanced WISEWOMAN project

Objective To determine if a clinic-based behavioral intervention program for low-income mid-life women that emphasizes use of community resources will increase moderate intensity physical activity (PA) and improve dietary intake. Methods Randomized trial conducted from May 2003 to December 2004 at one community health center in Wilmington, NC. A total of 236 women, ages 40–64, were randomized to receive an Enhanced Intervention (EI) or Minimal Intervention (MI). The EI consisted of an intensive phase (6 months) including 2 individual counseling sessions, 3 group sessions, and 3 phone calls from a peer counselor followed by a maintenance phase (6 months) including 1 individual counseling session and 7 monthly peer counselor calls. Both phases included efforts to increase participants' use of community resources that promote positive lifestyle change. The MI consisted of a one-time mailing of pamphlets on diet and PA. Outcomes, measured at 6 and 12 months, included the comparison of moderate intensity PA between study groups as assessed by accelerometer (primary outcome) and questionnaire, and dietary intake assessed by questionnaire and serum carotenoids (6 months only). Results For accelerometer outcomes, follow-up was 75% at 6 months and 73% at 12 months. Though moderate intensity PA increased in the EI and decreased in the MI, the difference between groups was not statistically significant (p = 0.45; multivariate model, p = 0.08); however, moderate intensity PA assessed by questionnaire (92% follow-up at 6 months and 75% at 12 months) was greater in the EI (p = 0.01; multivariate model, p = 0.001). For dietary outcomes, follow-up was 90% for questionnaire and 92% for serum carotenoids at 6 months and 74% for questionnaire at 12 months. Dietary intake improved more in the EI compared to the MI (questionnaire at 6 and 12 months, p < 0.001; serum carotenoid index, p = 0.05; multivariate model, p = 0.03). Conclusion The EI did not improve objectively measured PA, but was associated with improved self-reported and objective measures of dietary intake.

Randomized clinical trial of the timing it right stroke family support program: Research protocol

Background Family caregivers provide invaluable support to stroke survivors during their recovery, rehabilitation, and community re-integration. Unfortunately, it is not standard clinical practice to prepare and support caregivers in this role and, as a result, many experience stress and poor health that can compromise stroke survivor recovery and threaten the sustainability of keeping the stroke survivor at home. We developed the Timing it Right Stroke Family Support Program (TIRSFSP) to guide the timing of delivering specific types of education and support to meet caregivers' evolving needs. The objective of this multi-site randomized controlled trial is to determine if delivering the TIRSFSP across the stroke care continuum improves caregivers' sense of being supported and emotional well-being. Methods/design Our multi-site single-blinded randomized controlled trial will recruit 300 family caregivers of stroke survivors from urban and rural acute care hospitals. After completing a baseline assessment, participants will be randomly allocated to one of three groups: 1) TIRSFSP guided by a stroke support person (health care professional with stroke care experience), delivered in-person during acute care and by telephone for approximately the first six to 12 months post-stroke; 2) caregiver self-directed TIRSFSP with an initial introduction to the program by a stroke support person, or; 3) standard care receiving the educational resource "Let's Talk about Stroke" prepared by the Heart and Stroke Foundation. Participants will complete three follow-up quantitative assessments 3, 6, and 12-months post-stroke. These include assessments of depression, social support, psychological well-being, stroke knowledge, mastery (sense of control over life), caregiving assistance provided, caregiving impact on everyday life, and indicators of stroke severity and disability. Qualitative methods will also be used to obtain information about caregivers' experiences with the education and support received and the impact on caregivers' perception of being supported and emotional well-being. Discussion This research will determine if the TIRSFSP benefits family caregivers by improving their perception of being supported and emotional well-being. If proven effective, it could be recommended as a model of stroke family education and support that meets the Canadian Stroke Best Practice Guideline recommendation for providing timely education and support to families through transitions.

Efficacy and safety of adalimumab in patients with non-radiographic axial spondyloarthritis: Results of a randomised placebo-controlled trial (ABILITY-1)

Purpose: To evaluate the efficacy and safety of adalimumab in patients with non-radiographic axial spondyloarthritis (nr-axSpA). Methods: Patients fulfilled Assessment of Spondyloarthritis international Society (ASAS) criteria for axial spondyloarthritis, had a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of ≥ 4, total back pain score of ≥ 4 (10 cm visual analogue scale) and inadequate response, intolerance or contraindication to non-steroidal anti-inflammatory drugs (NSAIDs); patients fulfilling modified New York criteria for ankylosing spondylitis were excluded. Patients were randomised to adalimumab (N=91) or placebo (N=94). The primary endpoint was the percentage of patients achieving ASAS40 at week 12. Efficacy assessments included BASDAI and Ankylosing Spondylitis Disease Activity Score (ASDAS). MRI was performed at baseline and week 12 and scored using the Spondyloarthritis Research Consortium of Canada (SPARCC) index. Results: Significantly more patients in the adalimumab group achieved ASAS40 at week 12 compared with patients in the placebo group (36% vs 15%, p<0.001). Significant clinical improvements based on other ASAS responses, ASDAS and BASDAI were also detected at week 12 with adalimumab treatment, as were improvements in quality of life measures. Inflammation in the spine and sacroiliac joints on MRI significantly decreased after 12 weeks of adalimumab treatment. Shorter disease duration, younger age, elevated baseline C-reactive protein or higher SPARCC MRI sacroiliac joint scores were associated with better week 12 responses to adalimumab. The safety profile was consistent with what is known for adalimumab in ankylosing spondylitis and other diseases. Conclusions: In patients with nr-axSpA, adalimumab treatment resulted in effective control of disease activity, decreased inflammation and improved quality of life compared with placebo. Results from ABILITY-1 suggest that adalimumab has a positive benefit-risk profile in active nr-axSpA patients with inadequate response to NSAIDs.

Living well with diabetes: 24-month outcomes from a randomized trial of telephone-delivered weight loss and physical activity intervention to improve glycemic control

OBJECTIVE: To evaluate the effectiveness of a telephone-delivered behavioral weight loss and physical activity intervention targeting Australian primary care patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Pragmatic randomized controlled trial of telephone counseling (n = 151) versus usual care (n = 151). Reported here are 18-month (end-of-intervention) and 24-month (maintenance) primary outcomes of weight, moderate-to-vigorous-intensity physical activity (MVPA; via accelerometer), and HbA1c level. Secondary outcomes include dietary energy intake and diet quality, waist circumference, lipid levels, and blood pressure. Data were analyzed via adjusted linear mixed models with multiple imputation of missing data. RESULTS: Relative to usual-care participants, telephone counseling participants achieved modest, but significant, improvements in weight loss (relative rate [RR] -1.42% of baseline body weight [95% CI -2.54 to -0.30% of baseline body weight]), MVPA (RR 1.42 [95% CI 1.06-1.90]), diet quality (2.72 [95% CI 0.55-4.89]), and waist circumference (-1.84 cm [95% CI -3.16 to -0.51 cm]), but not in HbA1c level (RR 0.99 [95% CI 0.96-1.02]), or other cardio-metabolic markers. None of the outcomes showed a significant change/deterioration over the maintenance period. However, only the intervention effect for MVPA remained statistically significant at 24 months. CONCLUSIONS: The modest improvements in weight loss and behavior change, but the lack of changes in cardio-metabolic markers, may limit the utility, scalability, and sustainability of such an approach.

Randomised clinical trial of a family-based lifestyle intervention for childhood obesity involving parents as the exclusive agents of change

Parent-centred interventions for childhood obesity aim to improve parents' skills and confidence in managing children's dietary and activity patterns, and in promoting a healthy lifestyle in their family. However, few studies assess changes in parenting over the course of treatment. This study describes the evaluation of a lifestyle-specific parenting program (Group Lifestyle Triple P) on multiple child and parent outcomes. One-hundred-and-one families with overweight and obese 4- to 11-year-old children participated in an intervention or waitlist control condition. The 12-week intervention was associated with significant reductions in child BMI z score and weight-related problem behaviour. At the end of the intervention, parents reported increased confidence in managing children's weight-related behaviour, and less frequent use of inconsistent or coercive parenting practices. All short-term intervention effects were maintained at one-year follow-up assessment, with additional improvements in child body size. The results support the efficacy of Group Lifestyle Triple P and suggest that parenting influences treatment outcomes. Further research is needed to evaluate the long-term effectiveness of the intervention and to elucidate the mechanisms of change. © 2010 Elsevier Ltd.

Architectural changes of the biceps femoris after concentric or eccentric training

Purpose To determine i) the architectural adaptations of the biceps femoris long head (BFlf) following concentric or eccentric strength training interventions; ii) the time course of adaptation during training and detraining. Methods Participants in this randomized controlled trial (control [n=28], concentric training group [n=14], eccentric training group [n=14], males) completed a 4-week control period, followed by 6 weeks of either concentric- or eccentric-only knee flexor training on an isokinetic dynamometer and finished with 28 days of detraining. Architectural characteristics of BFlf were assessed at rest and during graded isometric contractions utilizing two-dimensional ultrasonography at 28 days pre-baseline, baseline, days 14, 21 and 42 of the intervention and then again following 28 days of detraining. Results BFlf fascicle length was significantly longer in the eccentric training group (p<0.05, d range: 2.65 to 2.98) and shorter in the concentric training group (p<0.05, d range: -1.62 to -0.96) after 42 days of training compared to baseline at all isometric contraction intensities. Following the 28-day detraining period, BFlf fascicle length was significantly reduced in the eccentric training group at all contraction intensities compared to the end of the intervention (p<0.05, d range: -1.73 to -1.55). There was no significant change in fascicle length of the concentric training group following the detraining period. Conclusions These results provide evidence that short term resistance training can lead to architectural alterations in the BFlf. In addition, the eccentric training-induced lengthening of BFlf fascicle length was reversed and returned to baseline values following 28 days of detraining. The contraction mode specific adaptations in this study may have implications for injury prevention and rehabilitation.

Nutritional support in children with end-stage liver disease : a randomized crossover trial of a branched-chain amino acid supplement

Malnutrition is common in children with end-stage liver disease (ESLD) awaiting orthotopic liver transplantation (OLT), and nutritional support is assuming an important role in preoperative management. To evaluate preoperative nutritional therapy, 19 children (median age 1.25 y) with ESLD awaiting OLT were prospectively studied. Two high-energy, isoenergetic and isonitrogenous nutritional formulations delivered nasogastrically were compared: a branched-chain amino acid (BCAA)-enriched semielemental formulation and a matched standard semielemental formulation. Twelve of 19 patients completed a randomized controlled study before OLT and 10 of 19 completed a full crossover study. Improvements in weight and height occurred during the BCAA supplements, with no statistical change on the standard formulation. Significant increases in total body potassium, midupper arm circumference, and subscapular skinfold thickness occurred during the BCAA supplements, whereas no significant changes occurred during the standard formulation period. Significantly fewer albumin infusions were required during the BCAA supplement. These findings suggest that BCAA-enriched formulas have advantages over standard semielemental formulas in improving nutritional status in children with ESLD. and are deserving of wider application and study.