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Abstract: Background and rationale: Cancer-related fatigue is a common severe symptom in breast cancer patients, especially during chemotherapy. Exercise appears to be promising in prevention or treatment of fatigue. Resistance training as an accompanying treatment to chemotherapy has been minimally investigated, yet might counteract muscle degradation and inflammation caused by many chemotherapeutics, and thus forestall or reduce fatigue. Previous exercise trials mostly compared the intervention with ‘usual care’. Therefore, it is unclear to what extent the observed effects on fatigue are based on physical adaptations by exercise itself, or rather on psycho-social factors linked to the group support or attention by the trainer. Methods and design: The BEATE study is a randomized, controlled intervention trial comparing a 12-week supervised progressive resistance training program with a supervised group-based progressive muscle relaxation training in 100 patients with breast cancer under adjuvant chemotherapy. The primary endpoint is cancer-related fatigue; secondary endpoints include quality of life, depression, and cognitive capacity. In addition, isokinetic and isometric muscle strength, cardiorespiratory fitness, and body composition are measured, and biomarkers, such as inflammatory parameters, cortisol, and oxidative stress are analyzed in blood, saliva and urine. Safety of the resistance training during chemotherapy is monitored. Discussion: Strengths of the BEATE study include the investigation of progressive resistance training parallel with chemotherapy, the choice of a control group that enables an evaluation of the physiological effects of exercise beyond potential psycho-social effects, and the comprehensive and high-quality assessment of physiological factors and biomarkers potentially related to fatigue. [Copyright &y& Elsevier]

Abstract: Background: The Melbourne Infant Feeding, Activity and Nutrition Trial (InFANT) Program, is a community-based, cluster-randomised controlled trial of an obesity prevention intervention delivered to first-time parents of infants from age 4–20 months. Conducted from 2008 to 2010, the program had high uptake and retention and showed positive impacts on some dietary outcomes and television viewing. Funding was secured for a follow-up study of participants two and 3.5years post intervention (at child ages ~3.5 and 5years). The follow-up study aims to assess intervention effects, mediators and moderators of effects, and program cost-effectiveness over the longer term. Methods/design: The 492 families still enrolled in the Melbourne InFANT Program at intervention conclusion will be recontacted and renewed consent sought to participate in this follow-up study. No further intervention will occur. Home visit data collections will occur approximately two and 3.5years post intervention. Main outcomes to be assessed include child body mass index, waist circumference, diet (3×24-hour recalls; food frequency questionnaire), physical activity (8days ActiGraph accelerometer data; parent reported active play) and sedentary time (8days ActiGraph accelerometer and ActivPAL inclinometer data; parent reported screen time). Discussion: Follow-up of participants of the Melbourne InFANT Program at two and 3.5years post intervention will allow assessment of longer term intervention effects, investigation of potential mediators and moderators of such effects, and economic evaluation of the longer term outcomes. This information will be valuable to researchers and policy makers in progressing the field of early childhood obesity prevention. [Copyright &y& Elsevier]

Abstract: Background: Comparative effectiveness research (CER) evidence on childhood obesity provides the basis for effective screening and management strategies in pediatric primary care. The uses of health information technology including decision support tools in the electronic health records (EHRs), as well as remote and mobile support to families, offer the potential to accelerate the adoption of childhood obesity CER evidence. Methods/design: The Study of Technology to Accelerate Research (STAR) is a three-arm, cluster-randomized controlled trial being conducted in 14 pediatric offices in Massachusetts designed to enroll 800, 6 to 12year old children with a body mass index (BMI)≥95th percentile seen in primary care at those practices. We will examine the extent to which computerized decision support tools in the EHR delivered to primary care providers at the point of care, with or without direct-to-parent support and coaching, will increase adoption of CER evidence for management of obese children. Direct-to-parent intervention components include telephone coaching and twice-weekly text messages. Point-of-care outcomes include obesity diagnosis, nutrition and physical activity counseling, and referral to weight management. One-year child-level outcomes include changes in BMI and improvements in diet, physical activity, screen time, and sleep behaviors, as well as cost and cost-effectiveness. Conclusions: STAR will determine the extent to which decision support tools in EHRs with or without direct-to-parent support will increase adoption of evidence-based obesity management strategies in pediatric practice and improve childhood obesity-related outcomes. [Copyright &y& Elsevier]

Abstract: The Comprehensive Assessment of the Long-term Effects of Reducing Intake of Energy Phase 2 (CALERIE) study is a systematic investigation of sustained 25% calorie restriction (CR) in non-obese humans. CALERIE is a multicenter (3 clinical sites, one coordinating center), parallel group, randomized controlled trial. Participants were recruited, screened, and randomized to the CR or control group with a 2:1 allocation. Inclusion criteria included ages 21–50years for men and 21–47years for women, and a body mass index (BMI) of 22.0≤BMI<28.0kg/m2. Exclusion criteria included abnormal laboratory markers, significant medical conditions, psychiatric/behavioral problems, and an inability to adhere to the rigors of the evaluation/intervention schedule. A multi-stage screening process (telephone screen and 3 in-clinic visits) was applied to identify eligible participants. Recruitment was effective and enrollment targets were met on time. 10,856 individuals contacted the clinical sites, of whom 9787 (90%) failed one or more eligibility criteria. Of the 1069 volunteers who started the in-clinic screening, 831 (78%) were either ineligible or dropped. 238 volunteers were enrolled (i.e., initiated the baseline evaluations), 220 were randomized, and 218 started the assigned intervention (2% from the first screening step). This study offered lessons for future multi-center trials engaging non-disease populations. Recruitment strategies must be tailored to specific sites. A multi-disciplinary screening process should be applied to address medical, physical, and psychological/behavioral suitability of participants. Finally, a multi-step screening process with simple criteria first, followed by more elaborate procedures has the potential to reduce the use of study resources. [Copyright &y& Elsevier]

Abstract: This paper presents the rationale and design features of the MeTeOR Trial (Meniscal Tear in Osteoarthritis Research; Clinical Trials.gov NCT00597012). MeTeOR is an NIH-funded seven-center prospective randomized controlled trial (RCT) designed to establish the efficacy of arthroscopic partial meniscectomy combined with a standardized physical therapy program as compared with a standardized physical therapy program alone in patients with a symptomatic meniscal tear in the setting of mild to moderate knee osteoarthritic change (OA). The design and execution of a trial that compares surgery with a nonoperative treatment strategy presents distinctive challenges. The goal of this paper is to provide the clinical rationale for MeTeOR and to highlight salient design features, with particular attention to those that present clinical and methodologic challenges. [Copyright &y& Elsevier]

Abstract: Introduction: Lyme disease (Lyme borreliosis) is caused by the tick-borne spirochete Borrelia burgdorferi. Long-term persistent illness following antibiotic treatment is not uncommon, particularly when treatment is delayed. Current treatment guidelines for persistent disease primarily rely on findings from four randomized, controlled trials (RCTs), strongly advising against retreatment. Methods: We performed a biostatistical review of all published RCTs evaluating antibiotic retreatment, focusing on trial design, analysis and conclusions. Results: Four RCTs met the inclusion criteria; all examined the efficacy of intravenous ceftriaxone versus placebo at approximately 3 or 6months. Design assumptions for the primary outcomes in the two Klempner trials and two outcomes in the Krupp trial were unrealistic and the trials were likely underpowered to detect clinically meaningful treatment effects. The Klempner trials were analyzed using inefficient statistical methods. The Krupp RCT was well-designed and analyzed for fatigue, finding statistically significant and clinically meaningful improvement. Fallon corroborated this finding. Fallon also found improvement in cognitive functioning, a primary outcome, at 12weeks which was not sustained at 24weeks; improvements in physical functioning and pain were demonstrated at week 24 as an interaction effect between treatment and baseline symptom severity with the drug effect increasing with higher baseline impairment. Discussion: This biostatistical review reveals that retreatment can be beneficial. Primary outcomes originally reported as statistically insignificant were likely underpowered. The positive treatment effects of ceftriaxone are encouraging and consistent with continued infection, a hypothesis deserving additional study. Additional studies of persistent infection and antibiotic treatment are warranted. [Copyright &y& Elsevier]

Abstract: The benefits of exercise for aging have received considerable attention in both the popular and academic press. The putative benefits of exercise for maximizing cognitive function and supporting brain health have great potential for combating Alzheimer''s disease (AD). Aerobic exercise offers a low-cost, low-risk intervention that is widely available and may have disease modifying effects. Demonstrating that aerobic exercise alters the AD process would have enormous public health implications. The purpose of this paper is to report the protocol of a current, community-based pilot study of aerobic exercise for AD to guide future investigation. This manuscript provides 1) an overview of possible benefits of exercise in those with dementia, 2) a rationale and recommendations for implementation of a community-based approach, 3) recommendation for implementation of similar study protocols, and 4) unique challenges in conducting an exercise trial in AD. [Copyright &y& Elsevier]

Abstract: Dosing is potentially the most important decision that must be made when building or refining behavioral interventions. In this paper, we propose standardized terminology and reporting of dosing information, which would inform intervention development, refinement for dissemination, and systematic reviews of dose–response relationships. Dosing of interventions may be characterized by duration, frequency, and amount. To illustrate the value of operationalizing these three parameters to evaluate dose–response relationships, 31 published reports of behavioral interventions to increase adherence to antiretroviral therapy (ART) were reviewed. The ART literature was characterized by under-reporting of dosing parameters, heterogeneity in dosing schedules, and heterogeneity in type of control group, which complicate analysis of dose–response relationships in systematic review and determination of the optimal dose for intervention dissemination. Improved reporting of the three dosing parameters and comparison of intended to actual delivery can inform the identification of the most effective intervention doses and the efficient implementation of efficacious interventions in clinical practice. [Copyright &y& Elsevier]

Abstract: Introduction: Robotic assistance during laparoscopic surgery for pelvic organ prolapse rapidly disseminated across the United States without level I data to support its benefit over traditional open and laparoscopic approaches [1]. This manuscript describes design and methodology of the Abdominal Colpopexy: Comparison of Endoscopic Surgical Strategies (ACCESS) Trial. Methods: ACCESS is a randomized comparative effectiveness trial enrolling patients at two academic teaching facilities, UCLA (Los Angeles, CA) and Loyola University (Chicago, IL). The primary aim is to compare costs of robotic assisted versus pure laparoscopic abdominal sacrocolpopexy (RASC vs LASC). Following a clinical decision for minimally-invasive abdominal sacrocolpopexy (ASC) and research consent, participants with symptomatic stage≥II pelvic organ prolapse are randomized to LASC or RASC on the day of surgery. Costs of care are based on each patient''s billing record and equipment costs at each hospital. All costs associated with surgical procedure including costs for robot and initial hospitalization and any re-hospitalization in the first 6weeks are compared between groups. Secondary outcomes include post-operative pain, anatomic outcomes, symptom severity and quality of life, and adverse events. Power calculation determined that 32 women in each arm would provide 95% power to detect a $2500 difference in total charges, using a two-sided two sample t-test with a significance level of 0.05. Results: Enrollment was completed in May 2011. The 12-month follow-up was completed in May 2012. Conclusions: This is a multi-center study to assess cost as a primary outcome in a comparative effectiveness trial of LASC versus RASC. [Copyright &y& Elsevier]

Abstract: Depression affects 20–30% of people living with HIV/AIDS (PLWHA) in the U.S. and predicts greater sexual risk behaviors, lower antiretroviral (ARV) medication adherence, and worse clinical outcomes. Yet little experimental evidence addresses the critical clinical question of whether depression treatment improves ARV adherence and clinical outcomes in PLWHA with depression. The Strategies to Link Antidepressant and Antiretroviral Management at Duke, UAB, and UNC (SLAM DUNC) Study is a randomized clinical effectiveness trial funded by the National Institute for Mental Health. The objective of SLAM DUNC is to test whether a depression treatment program integrated into routine HIV clinical care affects ARV adherence. PLWHA with depression (n=390) are randomized to enhanced usual care or a depression treatment model called Measurement-Based Care (MBC). MBC deploys a clinically supervised Depression Care Manager (DCM) to provide evidence-based antidepressant treatment recommendations to a non-psychiatric prescribing provider, guided by systematic and ongoing measures of depressive symptoms and side effects. MBC has limited time requirements and the DCM role can be effectively filled by a range of personnel given appropriate training and supervision, enhancing replicability. In SLAM DUNC, MBC is integrated into HIV care to support HIV providers in antidepressant prescription and management. The primary endpoint is ARV adherence measured by unannounced telephone-based pill counts at 6months with follow-up to 12months and secondary endpoints including viral load, health care utilization, and depressive severity. Important outcomes of this study will be evidence of the effectiveness of MBC in treating depression in PLWHA and improving HIV-related outcomes. [Copyright &y& Elsevier]

Abstract: Testosterone levels decrease with age. This decline is steeper during “critical illnesses”. Cardiac surgery is a particular representative model of major clinical condition producing stress responses similar to those observed during severe nonsurgical illness. Cardiac revascularization with extracorporeal circulation is characterized by marked postoperative complications such as insulin resistance, a pro-inflammatory state, acute anemia and renal dysfunction. These phenomena are more evident in older subjects, who are particularly vulnerable in the post-operative state, a condition that has been recently termed as “acute postoperative frailty”. We recently showed that in older men with low ejection fraction undergoing cardiac revascularization with extracorporeal circulation, there is a profound decline in anabolic hormones, including testosterone. After surgery testosterone concentration frequently declines to less than 200ng/dl, a situation suggestive of overt hypogonadism. Since men with low testosterone levels have a high probability of developing mobility limitations, we considered this a rationale for the perioperative use of testosterone treatment in older men undergoing cardiac revasularization surgery. We hypothesized that testosterone supplementation at this time might attenuate the impressive post-surgical catabolic hormonal milieu. The aim of this manuscript is to elucidate an ongoing randomized clinical trial in older men (70+ years old) undergoing elective cardiovascular revascularization with extracorporeal circulation. This randomized clinical trial will evaluate the effects of intramuscular testosterone administration on clinical and functional outcomes in this population. The study will also address potential mechanisms underlying the expected beneficial effects of testosterone supplementation including improvement of insulin sensitivity, markers of inflammatory status and improved hemoglobin levels. [Copyright &y& Elsevier]

Abstract: There are few effective obesity interventions directed towards younger children, particularly young minority children. This paper describes the design, intervention, recruitment methods, and baseline data of the ongoing Positive Lifestyles for Active Youngsters (Team PLAY) study. This randomized controlled trial is designed to test the efficacy of a 6-month, moderately intense, primary care feasible, family-based behavioral intervention, targeting both young children and their parent, in promoting healthy weight change. Participants are 270 overweight and obese children (ages 4 to 7years) and their parents, who were recruited from a primarily African American urban population. Parents and children were instructed in proven cognitive behavioral techniques (e.g. goal setting, self-talk, stimulus control and reinforcement) designed to encourage healthier food choices (more whole grains, fruits and vegetables, and less concentrated fats and sugar), reduce portion sizes, decrease sweetened beverages and increase moderate to vigorous physical activity engagement. The main outcome of this study is change in BMI at two year post enrollment. Recruitment using reactive methods (mailings, TV ads, pamphlets) was found to be more successful than using only a proactive approach (referral through physicians). At baseline, most children were very obese with an average BMI z-score of 2.6. Reported intake of fruits and vegetables and minutes of moderate to vigorous physical activity engagement did not meet national recommendations. If efficacious, Team PLAY would offer a model for obesity treatment directed at families with young children that could be tested and translated to both community and primary care settings. [Copyright &y& Elsevier]

Abstract: There is growing interest in promoting health for people with disabilities, yet evidence regarding community-based interventions is sparse. This paper describes the design details of a randomized controlled trial (RCT) that will test the effectiveness of a multi-component behaviorally based, intervention to promote exercise adoption (over 6months) and maintenance (up to one year) among wheelchair users and includes descriptive data on participant characteristics at baseline. Participants were randomly assigned to either a staff-supported intervention group or a self-guided comparison group. The primary study aim is to assess the effectiveness of the multi-component behaviorally based intervention for promoting physical activity adoption and maintenance. The RCT will also assess the physical and psychosocial effects of the intervention and the complex interplay of factors that influence the effectiveness of the intervention. Therefore, the primary outcome derives from participant reports of weekly exercise (type, frequency, duration) over 52weeks. Secondary outcomes collected on four occasions (baseline, 3months, 6months, 12months) included physiological outcomes (VO2 peak, strength), disability-related outcomes (pain, fatigue, participation), and psychosocial outcomes (exercise self-efficacy, exercise barriers, quality of life, depression, mood). This study will provide evidence regarding the effectiveness of a multi-component behaviorally based intervention for promoting exercise adoption among people with mobility impairments that necessitate wheelchair use. [Copyright &y& Elsevier]

Abstract: The purpose of this report is to identify factors associated with attrition and adherence of young women to a 16-week randomized aerobic exercise intervention on biomarkers associated with breast cancer risk. The exercise group was prescribed a progressive weight-bearing aerobic exercise program consisting of 30 minute workouts, 5 times/wk for 16weeks. Adherence was calculated as the average minutes of exercise per week during participation in the study. Of the total of 212 women randomized into the exercise intervention 46 dropped out, of which 82.5% dropped out during the earlier stages of exercise suggesting that reasons for withdrawal may have been related to difficulties with initiating physical activity. Time commitment or lack of time was the primary reason for withdrawal. Drop outs reported lower physical activity at baseline than study completers (p=.0007). Although 78% of the 212 randomized participants completed the exercise intervention, only 4.7% of the participants exercised for at least 150min/wk during the entire study period. Significant predictors of adherence were self-reported physical activity at baseline and depression scores. We conclude that predictors of adherence to exercise in our population of young women are similar to those reported for older adults. We also found that young women are more likely to exercise at moderate to vigorous intensity for 90 to 120min rather than 150min per week, even when participating in a highly structured exercise intervention. [Copyright &y& Elsevier]

Abstract: Disasters occur with high frequency throughout the world and increase risk for development of mental health problems in affected populations. Research focused on the development and evaluation of secondary prevention interventions addressing post-disaster mental health has high potential public-health impact. Toward this end, internet-based interventions (IBIs) are particularly attractive in that they: (1) offer a low-cost means of delivering standardized, targeted, personalized intervention content to a broad audience; and (2) are easily integrated within a stepped care approach to screening and service delivery. We describe a unique study design intended to evaluate an IBI with a disaster-affected population-based sample. Description and rationale are provided for sampling selection and procedures, selection of assessment measures and methods, design of the intervention, and statistical evaluation of critical outcomes. Unique features of this intervention include the use of a population-based sample, telephone and internet-based assessments, and development of a highly individualized web-based intervention. Challenges related to the development and large-scale evaluation of IBIs targeting post-disaster mental health problems, as well as implications for future research and practice are discussed. [Copyright &y& Elsevier]

Abstract: Data from laboratory studies, observational research, and/or secondary prevention trials suggest that vitamin D and marine omega-3 fatty acids may reduce risk for cancer or cardiovascular disease (CVD), but primary prevention trials with adequate dosing in general populations (i.e., unselected for disease risk) are lacking. The ongoing VITamin D and OmegA-3 TriaL (VITAL) is a large randomized, double-blind, placebo-controlled, 2x2 factorial trial of vitamin D (in the form of vitamin D3 [cholecalciferol], 2000IU/day) and marine omega-3 fatty acid (Omacor® fish oil, eicosapentaenoic acid [EPA]+docosahexaenoic acid [DHA], 1g/day) supplements in the primary prevention of cancer and CVD among a multi-ethnic population of 20,000 U.S. men aged ≥50 and women aged ≥55. The mean treatment period will be 5years. Baseline blood samples will be collected in at least 16,000 participants, with follow-up blood collection in about 6000 participants. Yearly follow-up questionnaires will assess treatment compliance (plasma biomarker measures will also assess compliance in a random sample of participants), use of non-study drugs or supplements, occurrence of endpoints, and cancer and vascular risk factors. Self-reported endpoints will be confirmed by medical record review by physicians blinded to treatment assignment, and deaths will be ascertained through national registries and other sources. Ancillary studies will investigate whether these agents affect risk for diabetes and glucose intolerance; hypertension; cognitive decline; depression; osteoporosis and fracture; physical disability and falls; asthma and other respiratory diseases; infections; and rheumatoid arthritis, systemic lupus erythematosus, thyroid diseases, and other autoimmune disorders. [Copyright &y& Elsevier]

Abstract: Animal studies have shown that life span is extended by caloric restriction (CR). This manuscript describes the design and methodology of an innovative CR intervention, which is the treatment arm of the CALERIE Study. This study is a multi-center, randomized controlled trial examining the effects of 2years of CR on biomarkers of longevity among non-obese (BMI≥22kg/m2 and <28kg/m2) adults. CALERIE is the first investigation of the effects of long-term CR on the aging process in non-obese humans. 220 healthy volunteers across 3 sites were recruited beginning in May 2007. Participants were randomized in a 2:1 ratio between the CR or control group (i.e., ad libitum diet). An intensive intervention was designed to assist participants in adhering to the 25% CR prescription for a two-year duration. The intervention was designed to optimize the likelihood that 25% CR would be achieved through a variety of nutritional and behavioral strategies, several of which are innovative methods for achieving CR. The intervention includes the following components: an intensive, “mixed” format schedule of group/individual sessions, meal provision phase with exposure to various diets, Personal Digital Assistants to monitor caloric intake, unique portion estimation training, tailored treatment using a computer tracking system, toolbox strategies and algorithms, as well as comprehensive coverage of nutrition and behavioral topics in order to assist participants in meeting their CR goal. This manuscript provides an overview of the CR intensive intervention and may be of assistance for other researchers and clinicians in designing future trials. [Copyright &y& Elsevier]

Abstract: Background: Deep vein thrombosis (DVT) frequently occurs in high-risk cardiovascular patients receiving orthopedic surgery, despite prophylactic measures for its prevention. Statins, a class of drugs used to lower cholesterol levels, have been reported to help prevent the development of DVT. Methods: We will conduct a prospective randomized clinical trial to compare the effects of high-dose rosuvastatin plus a low-molecular-weight heparin (LMWH), enoxaparin, with conventional LMWH therapy in the prevention of DVT. Patients will be naive to both statins and anti-coagulants and then underwent total knee replacement arthroplasty (TKRA). In total, 180 patients will be randomized into two groups of 90, consisting of a LMWH group (40mg enoxaparin subcutaneously beginning at 12h prior to surgery and continuing for 7days every 24h after surgery) and a statin plus LMWH group (20mg rosuvastatin orally for 14days, 7days before and after surgery in combination with LMWH). All patients will undergo computed tomography angiography of both extremities 7days after index surgery to assess the development of DVT. Discussion: DVT remains prevalent despite the use of conventional prophylactic measures, in part because certain patients (particularly the elderly) are unable to receive preventive treatment because of a high risk of bleeding complications and co-morbidity. Statins have been shown to have beneficial effects in arterial atherothrombosis and are frequently administered to elderly patients to treat coronary artery. We hypothesize that peri-operative statin treatment may be beneficial in those patients restricted from the conventional prophylaxis for DVT. [Copyright &y& Elsevier]

Abstract: Individuals with cancer are disproportionately affected by sleep disturbances, relative to the general population. These problems can be a consequence of the psychological, behavioral and physical effects of a cancer diagnosis and treatment. Sleep disturbances often persist for years and, when combined with already high levels of cancer-related distress, may place cancer survivors at a higher risk of future psychopathology, health problems and poorer quality of life. It is important to develop and evaluate treatments that comprehensively address the common symptom profiles experienced by cancer survivors. Methods: This study is a randomized controlled non-inferiority trial comparing Cognitive Behavior Therapy for Insomnia (CBT-I; a known efficacious treatment) to Mindfulness-Based Stress Reduction (MBSR; a treatment with demonstrated potential). This design can efficiently compare these two treatments directly and determine whether MBSR performs to the same standard as CBT-I for the treatment of insomnia with additional benefits of reducing cancer-related distress. Participants are randomly assigned to an 8-week CBT-I or MBSR group. Sleep indices are measured using subjective (sleep diaries) and objective (actigraphy) assessment tools. The primary outcome is insomnia severity. Secondary outcomes include sleep quality, symptoms of stress, mood disturbance, mindfulness, and dysfunctional beliefs and attitudes toward sleep. Assessments are completed at three time periods: pre-treatment, post-treatment and at 3month follow up. Conclusions: Considering the high prevalence of distress and sleep disturbances in the cancer population, should MBSR produce sleep effects comparable to CBT-I, it may be more comprehensive — making it the treatment of choice for addressing cancer-related psychological sequelae. [Copyright &y& Elsevier]

Abstract: People with advanced pulmonary disease (APD), such as those with chronic obstructive pulmonary disease, have markedly impaired quality of life. Home Oxygen Therapy (HOT) itself is burdensome, although it often improves survival duration and quality of life in these patients. The exact burdens on informal caregivers of these patients are unknown. The central purpose of the pragmatic randomized controlled study described in this protocol is to determine the effectiveness of improving the skills and knowledge of carers of patients with APD who use HOT. Specifically we aimed to estimate the incremental impact of this carer intervention above usual care on health, economic, psychological and social domains for patient and carer dyads relative to the level of current burden. Eligible patients and their carers were recruited through three major hospitals, and randomized to an intervention or control group. The carers in the intervention group received two home-delivered education sessions based on the principles of academic detailing. Participants are currently being followed over 12months. The primary outcome will be the proportion of patients surviving without a chronic obstructive pulmonary disease-related readmission / residential (non respite) care over 12months. Carer secondary outcomes include perceived caregiver burden, level of expected and received social support, perceived level of mastery, self esteem, health related quality of life and disability, and ability to conduct domestic chores and household maintenance, social activities and provide service to others, and fatigue. Secondary patient outcomes include health related quality of life and disability, and current respiratory health status. [Copyright &y& Elsevier]

Abstract: Background: Prevention of childhood obesity is a public health priority. Parents influence a child''s weight by modeling healthy behaviors, controlling food availability and activity opportunities, and appropriate feeding practices. Thus interventions should target education and behavioral change in the parent, and positive, mutually reinforcing behaviors within the family. Methods: This paper presents the design, rationale and baseline characteristics of Kids and Adults Now! — Defeat Obesity (KAN-DO), a randomized controlled behavioral intervention trial targeting weight maintenance in children of healthy weight, and weight reduction in overweight children. 400 children aged 2–5 and their overweight or obese mothers in the Triangle and Triad regions of North Carolina are randomized equally to control or the KAN-DO intervention, consisting of mailed family kits encouraging healthy lifestyle change. Eight (monthly) kits are supported by motivational counseling calls and a single group session. Mothers are targeted during a hypothesized “teachable moment” for health behavior change (the birth of a new baby), and intervention content addresses: parenting skills ((e.g., emotional regulation, authoritative parenting), healthy eating, and physical activity. Results: The 400 mother–child dyads randomized to trial are 75% white and 22% black; 19% have a household income of $30,000 or below. At baseline, 15% of children are overweight (85th–95th percentile for body mass index) and 9% are obese (≥95th percentile). Conclusion: This intervention addresses childhood obesity prevention by using a family-based, synergistic approach, targeting at-risk children and their mothers during key transitional periods, and enhancing maternal self-regulation and responsive parenting as a foundation for health behavior change. [Copyright &y& Elsevier]

Abstract: The use of blinding strengthens the credibility of randomized controlled trials (RCTs) by minimizing bias. However, there is confusion surrounding the definition of blinding as well as the terms single, double, and triple blind. It has been suggested that these terms should be discontinued due to their broad misinterpretation. We recommend that, instead of abandoning the use of these terms, explicit definitions of blinding should be adopted. We address herein the concept of blinding, propose standard definitions for the consistent use of these terms, and detail when different types of blinding should be utilized. Standardizing the definition of blinding and utilizing proper blinding methods will improve the quality and clarity of reporting in RCTs. [Copyright &y& Elsevier]

Abstract: Designing cluster randomized trials in clinical studies often requires accurate estimates of intraclass correlation, which quantifies the strength of correlation between units, such as participants, within a cluster, such as a practice. Published ICC estimates, even when available, often suffer from the problem of wide confidence intervals. Using data from a national, randomized, controlled study concerning violence prevention for children—the Safety Check—we compare the ICC values derived from two approaches only baseline data and using both baseline and follow-up data. Using a variance component decomposition approach, the latter method allows flexibility in handling complex data sets. For example, it allows for shifts in the outcome variable over time and for an unbalanced cluster design. Furthermore, we evaluate the large-sample formula for ICC estimates and standard errors using the bootstrap method. Our findings suggest that ICC estimates range from 0.012 to 0.11 for providers within practice and range from 0.018 to 0.11 for families within provider. The estimates derived from the baseline-only and repeated-measurements approaches agree quite well except in cases in which variation over repeated measurements is large. The reductions in the widths of ICC confidence limits from using repeated measurement over baseline only are, respectively, 62% and 42% at the practice and provider levels. The contribution of this paper therefore includes two elements, which are a methodology for improving the accuracy of ICC, and the reporting of such quantities for pediatric and other researchers who are interested in designing clustered randomized trials similar to the current study. [Copyright &y& Elsevier]

Abstract: To evaluate strategies to reduce HIV-1 transmission through breastfeeding, a multicentre study including a nested randomized controlled trial was implemented in five research sites in West, East and South Africa (The Kesho Bora Study). The aim was to optimize the use of antiretroviral (ARV) drugs during pregnancy, delivery and breastfeeding to prevent mother-to-child transmission of HIV-1 (PMTCT) and to preserve the health of the HIV-1-infected mother. The study included long-term ARV treatment for women with advanced disease, and short-course ARV prophylaxis stopped at delivery for women with early disease. Women with intermediate disease participated in a randomized controlled trial to compare safety and efficacy of triple-ARV prophylaxis prolonged during breastfeeding with short-course ARV prophylaxis stopped at delivery. Between January 2005 and August 2008 a total of 1140 women were enrolled. This paper describes the study design, interventions and protocol amendments introduced to adapt to evolving scientific knowledge, international guidelines and availability of ARV treatment. The paper highlights the successes and challenges during the conduct of the trial. The Kesho Bora Study included one of the few randomized controlled trials to assess safety and efficacy of ARV prophylaxis continued during breastfeeding and the only randomized trial to assess maternal prophylaxis started during pregnancy. The findings have been important for informing international and national guidelines on MTCT prevention in developing countries where, due to poverty, lack of reliable and affordable supply of replacement feed and stigma associated with HIV/AIDS, HIV-infected women have little or no option other than to breastfeed their infants. (ISRCTN71468401). [ABSTRACT FROM AUTHOR]

Abstract: Healthy Living Partnerships to Prevent Diabetes (HELP PD) is a randomized controlled trial designed to translate the Diabetes Prevention Program (DPP) lifestyle intervention into a community setting using community health workers engaged through an existing Diabetes Care Center (DCC). Overweight and obese (BMI 25–40kg/m2) individuals with pre-diabetes (fasting blood glucose 95–125mg/dl) with no medical contraindications to participate in a lifestyle intervention were recruited for participation in this study. Standard recruitment strategies were employed, including mass mailing, direct provider referral, and community events. Participant recruitment and randomization for this trial began in 2007 and was concluded in 2009. 1818 screenings were conducted; of these, 326 (17.9%) qualified and 301 (16.6%) participants were randomized over a 21month period. 23.8% of potential participants were excluded during the initial telephone screening, primarily for BMI and recent history of CVD. The majority of participants (220, 73.1%) reported mass mailing as their primary source of information about the study. Mass mailing was more effective with participants who identified themselves as white when compared to African-Americans. The cost of recruitment per randomized participant was $816, which includes direct costs and staff effort. 41% of the randomized participants were male and approximately 27% reported a race or ethnicity other than white. In comparison to the DPP study cohort, the HELP PD population is older, more educated and predominately white. These differences, reflecting in part the community in which HELP PD was conducted, may have implications for retention and adherence in the lifestyle intervention group. [ABSTRACT FROM AUTHOR]

Abstract: Introduction:: Psychological theory suggests that participants may be more likely to volunteer to join a clinical trial if they perceive places in the trial are a scarce commodity. Material and methods:: We conducted a single blind, randomized controlled trial to test recruitment strategies within the larger txt2stop smoking cessation trial. 1862 people who were eligible for the txt2stop trial but had not yet consented to join were randomized to receive either A) a reminder about the txt2stop trial plus a message that there were only 300 places left, or B) a reminder about the trial only. The outcome was the participant''s consent to join the txt2stop trial 3days after messages were sent. Results: Of 895 participants randomized to the intervention group, 90 (10.1%) had consented to join the txt2stop trial. Of the 967 participants randomized to the control group, 67 (6.9%) had consented to join the txt2stop trial (OR=1.50, 95% CI 1.07–2.12). Discussion: Scarcity messages were an effective way to increase recruitment into the txt2stop trial and could be relevant to other trials. Conclusions: Communicating scarcity is an effective way to increase trial recruitment. [Copyright &y& Elsevier]

Abstract: The Extension Family Lifestyle Intervention Project (E-FLIP for Kids) is a three-arm, randomized controlled trial assessing the effectiveness of two behavioral weight management interventions in an important and at-risk population, overweight and obese children and their parents in rural counties. Participants will include 240 parent–child dyads from nine rural counties in north central Florida. Dyads will be randomized to one of three conditions: (a) a Family-Based Behavioral Group Intervention, (b) a Parent-Only Behavioral Group Intervention, and (c) an Education Control Condition. Child and parent participants will be assessed at baseline (month 0), post-treatment (month 12) and follow-up (month 24). Assessment and intervention sessions will be held at Cooperative Extension Service offices within each participating county. The primary outcome measure is change in child BMI z-score. Additional key outcome measures include child body fat, waist circumference, dietary intake, physical activity, blood lipids, blood glucose, blood pressure, physical fitness, quality of life, and program and participants costs. Parent BMI, dietary intake, and physical activity also will be assessed. Randomized controlled trials testing the effectiveness of childhood obesity interventions in real-world community-based settings are extremely valuable, but much too rare. The E-FLIP for Kids trial will evaluate the impact of a community-based intervention delivered to families in rural settings utilizing the existing Cooperative Extension Service network on long-term child behavior, weight status and biological markers of diabetes and early cardiovascular disease. If successful, a Parent-Only intervention program may provide a cost-effective and practical intervention for families in underserved rural communities. [ABSTRACT FROM AUTHOR]

Abstract: Background: Medication errors are an important public health concern, and poor understanding of medication labels are a root cause. Research shows that labels are variable, of poor quality, and not patient-centered. No real-world trials have evaluated whether improved medication labels can affect appropriate medication use, adherence or health outcomes. Trial design: We developed an evidence-based prescription label that addresses both content and format. The enhanced label includes a universal medication schedule (UMS) that standardizes the directions for use incorporating 1) standard time periods for administration (morning, noon, evening, and bedtime), 2) numeric vs. alpha characters, 3) ‘carriage returns’ to separate daily dose and 4) a graphic aid to visually depict dose and frequency. We will evaluate the effect of providing this label to randomly sampled patients who receive their care from free clinics, mobile vans and federally qualified health centers (FQHCs) in Northern Virginia. We will recruit patients with diabetes or hypertension; these patients will be randomly assigned to receive all of their medications with improved labels or to receive prescriptions with standard labels. The primary outcome will be the patient''s ability to correctly demonstrate dosing instructions. Other outcomes include adherence, error rates and health outcomes. Conclusion: To our knowledge, this trial is the first to evaluate the effect of prescription label improvement on understanding, medication use and outcomes in a clinical setting. If successful, these findings could be implemented broadly to promote safe and appropriate medication use and to support evidence-based standards in the development of labels. [Copyright &y& Elsevier]

Abstract: Background: Screening decreases colorectal cancer (CRC) morbidity and mortality, yet remains underutilized. Screening breakdowns arise from lack of uptake and failure to follow-up after a positive screening test. Objectives: Systems of support to increase colorectal cancer screening and follow-up (SOS) is a randomized trial designed to increase: (1) CRC screening and (2) follow-up of positive screening tests. The Chronic Care Model and the Preventive Health Model inform study design. Methods: The setting is a large nonprofit healthcare organization. In part-1 study, patients age 50–75 due for CRC screening are randomized to one of 4 study conditions. Arm 1 receives usual care. Arm 2 receives automated support (mailed information about screening choices and fecal occult blood tests (FOBT)). Arm 3 receives automated and assisted support (a medical assistant telephone call). Arm 4 receives automated, assisted, and care management support (a registered nurse provides behavioral activation and coordination of care). In part-2, study patients with a positive FOBT or adenomas on flexible sigmoidoscopy are randomized to receive either usual care or nurse care management. Primary outcomes are: 1) the proportion with CRC screening, 2) the proportion with a complete diagnostic evaluation after a positive screening test. Results: We sent recruitment letters to 15,414 patients and 4675 were randomized. Randomly assigned treatment groups were similar in age, sex, race, education, self-reported health, and CRC screening history. Conclusions: We will determine the effectiveness and cost effectiveness of stepped increases in systems of support to increase CRC screening and follow-up after a positive screening test over 2years. [ABSTRACT FROM AUTHOR]

Abstract: The randomized controlled trial (RCT) is the gold standard for assessing the efficacy of medical treatments. Over the past 50years, RCT methodology has proven to be quite successful in identifying effective treatments and weeding out ineffective ones, thus transforming medicine from an intuitive art into an empirical science. However, the enormous success of the RCT has inadvertently contributed to a common inferential error that is insufficiently appreciated by some clinicians and researchers. Although RCTs can effectively distinguish between placebo and active treatment effects at the level of the group, contrary to intuition, this same disentanglement is much more difficult to achieve at the level of the individual. For individual patients it is surprisingly difficult to determine who is a treatment responder and who is not. Using data from a recent RCT, we illustrate the problem and detail its negative effects for research and clinical practice. Finally, we suggest strategies for minimizing these negative effects. [ABSTRACT FROM AUTHOR]

Abstract: Background: Recruitment to clinical trials is often slow and difficult, with a growing body of research examining this issue. However there is very little work related to stroke. Aims: The aim of this study was to examine the success and efficiency of recruitment of community-dwelling stroke survivors over the first two years of a clinical trial aiming to improve community ambulation. Method: Recruitment strategies fell into 2 broad categories: (i) advertisement (such as newspaper advertising and media releases), and (ii) referral (via hospital and community physiotherapists, a stroke liaison officer and other researchers). Records were kept of the number of people who were screened, were eligible and were recruited for each strategy. Results: The recruitment target of 60 in the first two years was not met. 111 stroke survivors were screened and 57 were recruited (i.e., a recruitment rate of 51%). The most successful strategy was referral via hospital-based physiotherapists (47% of recruited participants) and the least successful were media release and local newspaper advertising. The referral strategies were all more efficient than any of the advertisement strategies. Conclusions: In general, recruitment was inefficient and costly in terms of human resources. Given that stroke research is underfunded, it is important to find efficient ways of recruiting stroke survivors to clinical trials. An Australian national database similar to other disease-specific data bases (such as the National Cancer Database) is under development. In the interim, recruiting for several clinical trials at once may increase efficiency. [Copyright &y& Elsevier]

Abstract: Although the Diabetes Prevention Program (DPP) developed a lifestyle weight loss intervention that has been demonstrated to prevent type 2 diabetes in high-risk individuals, it has yet to be widely adopted at the community level. The Healthy Living Partnership to Prevent Diabetes study (HELP PD) was designed to translate the DPP approach for use in community settings as a cost-effective intervention led by Community Health Workers (CHW''s) and administered through a Diabetes Care Center (DCC). Approximately 300 overweight and obese (BMI 25-40kg/m2) individuals with prediabetes (fasting blood glucose 95-124mg/dl) were randomly assigned to either a lifestyle weight loss intervention (LW) or an enhanced usual care comparison condition (UC). The goal of LW is ≥7% weight loss achieved through increases in physical activity (180min/wk) and decreases in caloric intake (approximately 1500kcal/day). The intervention consists of CHW-led group-mediated cognitive behavioral meetings that occur weekly for 6months and monthly thereafter for 18months. UC consists of 2 individual meetings with a registered dietitian and a monthly newsletter. The primary outcome is change in fasting blood glucose. Secondary outcomes include cardiovascular risk factors, health-related quality of life, and social cognitive variables. Outcomes are masked and are collected every 6months. The cost-effectiveness of the program will also be assessed. A community-based program that is administered through local DCC''s and that harnesses the experience of community members (CHW''s) may be a promising strategy for the widespread dissemination of interventions effective at preventing type 2 diabetes in high risk individuals. [Copyright &y& Elsevier]

Abstract: Background : Nonalcoholic fatty liver disease (NAFLD) in children can lead to steatohepatitis, cirrhosis, and end-stage liver disease. The cause of NAFLD is unknown, but it is commonly associated with obesity, insulin resistance, and dyslipidemia. Objectives : TONIC is conducted to test whether treatment with metformin, an insulin sensitizer, or vitamin E, a naturally available antioxidant, will lead to improvements in biochemical and histological features of nondiabetic children with biopsy-proven NAFLD. Design : TONIC is a randomized, multicenter, double-masked, placebo-controlled trial of 96weeks of treatment with metformin or vitamin E. The primary outcome measure chosen for the trial is improvement in serum alanine aminotransferase (ALT) levels with treatment as compared to placebo. An improvement in ALT is defined as reduction in serum ALT levels to below 50% of the baseline values or into the normal range (40U/L or less) during the last 48weeks of treatment. Histological improvement is defined by changes in liver histology between a baseline and end-of-treatment liver biopsy in regards to (1) steatohepatitis, (2) NAFLD Activity Score, consisting of scores for steatosis, lobular inflammation, and hepatocellular injury (ballooning), and (3) fibrosis score. Methods : Between September 2005 and September 2007, 173 children were enrolled into TONIC at 10 clinical centers in the United States. Participants were randomized to receive either metformin (500mg b.i.d.), vitamin E (400IU b.i.d.), or placebo for 96weeks. This protocol was approved by all participating center Institutional Review Boards (IRBs) and an independent Data and Safety Monitoring Board (DSMB). (ClinicalTrials.gov number, NCT00063635.) [Copyright &y& Elsevier]

Abstract: In clinical trials of systemic therapy for advanced hepatocellular carcinoma (HCC), Asian trials almost always reported poorer survival than non-Asian trials. This study sought to identify contributory factors for this geographic difference. A systematic review was done on randomized trials for unresectable HCC that used systemic therapy as an experimental arm and placebo or supportive care as control. Meta-analysis was performed with the consideration of fixed and random effects. Then, meta-regression was performed to identify predictors of patient survival in the control arm and the treatment effects (improvement in median survival). Fourteen trials (6 Asians, 8 non-Asians) were eligible for meta-analysis. The median survival of patients in the control arm, which indicated natural history of advanced HCC patients, was 3.57±1.88months in Asian trials and 5.96±1.46months in non-Asian trials (p =0.02). Independent predictors of better survival included non-Asian trials (p =0.0007), higher percentage of Child A cirrhosis (p =0.01) and hepatitis B (HBV)-related HCC (p =0.02). Sub-group analysis suggested that Asian trials tended to enroll patients with more advanced diseases. Independent predictors of better treatment effect included non-Asian trials, higher percentage of extra-hepatic metastasis, HBV-related HCC, and poorer trial quality. The quantitative estimation of the geographic difference can help design of future clinical trials of advanced HCC. [Copyright &y& Elsevier]

Abstract: Translating evidence-based research into practice requires data from clinical trials in real world settings. This paper presents “lessons learned” from the implementation of an RCT of breastfeeding promotion interventions at two busy, urban, prenatal care sites. Data were obtained via direct observations, qualitative interviews, and study statistics. Primary challenges include: time and space burdens, “research vs. service” mission conflict, and the provider learning curve for conducting interventions. Primary facilitators include: researcher presence for enhancing rapport with participants and staff, site staff labeling of both the research interview and intervention as “value added time,” and the ability of research staff to assist the clinic beyond the scope of the clinical trial. Specific suggestions are given for building collaborative bonds between the research team, clinicians, administrators, and staff in busy urban practices. [Copyright &y& Elsevier]

Abstract: Acupuncture to treat Bell''s palsy is one of the most commonly used methods in China. There are a variety of acupuncture treatment options to treat Bell''s palsy in clinical practice. Since Bell''s palsy has three different path-stages (acute stage, resting stage and restoration stage), so whether acupuncture is effective in the different path-stages and which acupuncture treatment is the best method are major issues in acupuncture clinical trials about Bell''s palsy. In this article, we report the design and protocol of a large sample multi-center randomized controlled trial to treat Bell''s palsy with acupuncture. There are five acupuncture groups, with four according to different path-stages and one not. In total, 900 patients with Bell''s palsy are enrolled in this study. These patients are randomly assigned to receive one of the following four treatment groups according to different path-stages, i.e. 1) staging acupuncture group, 2) staging acupuncture and moxibustion group, 3) staging electro–acupuncture group, 4) staging acupuncture along yangming musculature group or non-staging acupuncture control group. The outcome measurements in this trial are the effect comparison achieved among these five groups in terms of House–Brackmann scale (Global Score and Regional Score), Facial Disability Index scale, Classification scale of Facial Paralysis, and WHOQOL–BREF scale before randomization (baseline phase) and after randomization. The result of this trial will certify the efficacy of using staging acupuncture and moxibustion to treat Bell''s palsy, and to approach a best acupuncture treatment among these five different methods for treating Bell''s palsy. [Copyright &y& Elsevier]

Abstract: Background: Little is known about the treatment of depression in older patients with heart failure. This study was developed to investigate the effectiveness of antidepressant treatment for major depressive disorder (MDD) in the elderly with heart failure. Methods: We enrolled 72 older outpatients with ejection fraction <50 and diagnosed with MDD by the structured clinical interview for DSM-IV. Thirty-seven patients, 19 on citalopram and 18 on placebo, initiated an 8-week double-blind treatment phase. Measurements were performed with the 31-item Hamilton Rating Scale for Depression (Ham-D-31), the Montgomery–Asberg rating scale (MADRS) and the Systematic Assessment for Treatment Emergent Effects (SAFTEE). A psychiatrist followed up the patients weekly, performing a consultation for about 20 min to field complaints after the measurements. Results: A trend toward superiority of citalopram over placebo in reducing depression was observed in MADRS scores (15.05+9.74 vs 9.44+9.25, P =.082) but not on HAM-D scores. The depressive symptomatology significantly decreased in both groups (P < .001). The high rate of placebo response during the double-blind phase (56.3%) led us to conclude the study at the interim analysis with 37 patients. Conclusion: Citalopram treatment of MDD in older patients with heart failure is well-tolerated with low rates of side effects, but was not significantly more effective than placebo in the treatment of depression. Weekly psychiatric follow-up including counseling may contribute to the improvement of depression in this population. Scales weighted on psychological symptoms such as the MADRS are possibly better suited to measure depression severity and improvement in patients with heart failure. [Copyright &y& Elsevier]

Abstract: Background:: Non-alcoholic steatohepatitis (NASH) is a common liver disease associated with obesity and diabetes. NASH is a progressive disorder that can lead to cirrhosis and liver failure. Insulin resistance and oxidative stress are thought to play important roles in its pathogenesis. There is no definitive treatment for NASH. Objectives:: PIVENS is conducted to test the hypotheses that treatment with pioglitazone, a thiazolidinedione insulin sensitizer, or vitamin E, a naturally available antioxidant, will lead to improvement in hepatic histology in non-diabetic adults with biopsy proven NASH. Design:: PIVENS is a randomized, multicenter, double-masked, placebo-controlled trial to evaluate whether 96 weeks of treatment with pioglitazone or vitamin E improves hepatic histology in non-diabetic adults with NASH compared to treatment with placebo. Before and post-treatment liver biopsies are read centrally in a masked fashion for an assessment of steatohepatitis and a NAFLD Activity Score (NAS) consisting of steatosis, lobular inflammation, and hepatocyte ballooning. The primary outcome measure is defined as either an improvement in NAS by 2 or more in at least two NAS features, or a post-treatment NAS of 3 or less, and improvement in hepatocyte ballooning by 1 or more, and no worsening of fibrosis. Methods:: PIVENS enrollment started in January 2005 and ended in January 2007 with 247 patients randomized to receive either pioglitazone (30 mg q.d.), vitamin E (800 IU q.d.), or placebo for 96 weeks. Participants will be followed for an additional 24 weeks after stopping the treatment. The study protocol incorporates the use of several validated questionnaires and specimen banking. This protocol was approved by all participating center Institutional Review Boards (IRBs) and an independent Data and Safety Monitoring Board (DSMB) which was established for monitoring the accumulated interim data as the trial progresses to ensure patient safety and to review efficacy as well as the quality of data collection and overall study management. (ClinicalTrials.gov number, NCT00063622.) [Copyright &y& Elsevier]

Abstract: The revised Consolidated Standards of Reporting Trials (CONSORT) statement recognizes the importance of including data so that readers are able to judge the reliability or relevance of randomized controlled trial (RCT) findings. However, it is unclear whether journals consistently report the pre-randomization information necessary to assess the general applicability of trial results. The objective of this study was to assess the extent of adherence to pre-randomization data reporting in 4 leading general medicine journals, as recommended by the revised CONSORT statement over a specific time frame. A total of 480 RCTs met the eligibility criteria for review. In 2004, 138 of 246 (56%) articles reported the full CONSORT pre-randomization information, of which 121 (88%) presented this information in diagram form. In 2006, 136 of 234 (58%) reported the full information, of which 127 (93%) presented the information in a diagram. These numbers indicate no improvement in the reporting of pre-randomization information. In conclusion, reporting of the full CONSORT data remains inconsistent. We recommend that journals continue to support the CONSORT statement and ensure that adequate information is provided upon submission before commencing the peer review process. The presentation of clear, precise data will ensure that readers are able to better interpret the applicability of findings. [Copyright &y& Elsevier]

Abstract: Background: In a typical clinical trial treatment effects will not be expected to be the same on all of the study participants. As a result, investigators are often tempted to look at the effects of a given treatment in subgroups of patients in order to determine who will benefit the most or the least, especially when the treatment effect in the total sample is insignificant or borderline. This paper aims at demonstrating the application of random effect models as one approach to identify subpopulations suitable for subgroup analysis in a longitudinal study. Methods: Data collected from a double-blind randomized controlled trial were used to demonstrate how multilevel modeling using random effects can be used to identify subgroups of postmenopausal women who benefit the most from nonhormonal treatment (gabapentin) of their hot flashes. Results: We estimated subject-specific treatment effects and correlated these effects with patient characteristics at baseline. We found that women with a higher severity of hot flashes score at baseline were more likely to have the greatest reduction in hot flashes score from the treatment. Also, women who had a serum creatinine level higher than the median level at baseline demonstrated a greater response to gabapentin compared to the placebo group. Conclusion: Our proposed method can help researchers identify patient factors that are associated with differential effect. Those factors are potential areas for further clinical investigation or for constructing subgroups for sub-analysis. [Copyright &y& Elsevier]

Over 100 million adults in the United States have hypertension. The DASH (Dietary Approaches to Stop Hypertension) eating pattern is an evidence-based first-line treatment option for hypertension; however, adherence to the DASH eating pattern at a population level remains low. To address this gap, we will implement Nourish, a randomized controlled efficacy trial that will leverage a commercially-available smartphone application and evidence-based behavior change principles to improve adherence to the DASH eating pattern among adults with hypertension. The Nourish trial is a two-arm, 12-month randomized control trial that will enroll adults (N = 300) with hypertension, defined as a systolic blood pressure of 120–159 mmHg; a diastolic blood pressure of 80–99 mmHg; and/or adults on blood pressure-lowering medication. Nourish will test the efficacy of a digital health intervention, as compared to the attention control arm, on DASH eating pattern adherence and blood pressure. Intervention components will include skills training, self-monitoring, personalized feedback, and responsive coaching. The primary outcome of the trial is 6-month changes in adherence to the DASH eating pattern, as measured by 24-h dietary recalls. Millions of Americans remain in need of effective behavioral interventions to manage and improve their hypertension and its adverse consequences. The ubiquity of smartphones offers a promising approach to disseminate the DASH eating pattern. By leveraging these widely used smartphone applications, combined with evidence-based behavior change principles and the DASH eating plan, Nourish will demonstrate the effectiveness of a digital health intervention to improve DASH adherence, and ultimately, to reduce blood pressure. Trial Number: NCT03875 [ABSTRACT FROM AUTHOR]

Clopidogrel and aspirin are key intervention for acute ischemic stroke (AIS) and transient ischemic attack (TIA). However, with increased clinical application, many patients have shown clopidogrel resistance (CR) and/or aspirin resistance (AR) that affect antiplatelet therapy on AIS/TIA. At present, there is no research reported on personalized antiplatelet therapy guidelines for patients with CR and/or AR. Our study aims to assess the effect of personalized antiplatelet therapy based on CYP2C19 genotype and urine 11-dhTxB2 tests in patients with AIS or TIA. This is a multi-center randomized controlled trial. Eligible patients with AIS/TIA from 14 comprehensive hospitals in Jiangxi province will be recruited after obtaining informed consent. Participants will be randomly divided into the intervention group and the control group at a ratio of 1:1. personalized antiplatelet therapy based on the CYP2C19 genotype/urine11-dhTxB2 tests will be given to the intervention group. Demographics, disease history, laboratory investigations, therapys, physiological tests, imaging reports and other clinical features will be collected. Clinical outcomes including stroke recurrence, Modified Rankin Scale (mRS) score, bleeding events and all-cause mortality will be assessed at the 1st, 3rd, 6th, and 12th-month post-discharge. Our study will conduct free antiplatelet resistance tests and personalized antiplatelet therapy for AIS/TIA patients with CR/AR, ultimately evaluating personalized therapy effectiveness through one-year follow-up. The research results will help to assess the impact of personalized antiplatelet therapy on the prognosis of stroke, thus providing reference for precise clinical treatment. • This study may provide a reference for clinical treatment and prescribing guidelines for AIS/TIA patients with clopidogrel and/or aspirin resistance.. • This study will explore the CYP2C19 genotype distribution and the frequency of aspirin resistanceand potential factors that affect the prognosis and safety in Chinese AIS/TIA patients. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Only a few Chinese medical journals have recommended CONSORT in their “Instruction for authors or Guide for authors”. This study aims to evaluate the reporting quality of randomized controlled trials (RCTs) published in the five leading Chinese medical journals indexed by MEDLINE. Methods: We identified RCTs published from 2004 to January 2007 in five leading Chinese medical journals by searching three important Chinese databases systematically, namely CNKI (China National Knowledge Infrastructure/Chinese Academic Journals full text Database), VIP (a full text database of China) and CBM disc (China Biomedicine Database Disc) and assessed the quality of each RCT by using the Consolidated Standards for Reporting of Trials (CONSORT) and the 5-point Jadad scale. Results: One hundred and forty two RCTs were included. Based on the items in the revised CONSORT statement, 130 (91.55%) of the 142 RCTs mentioned “randomization” in the title or abstract, but only 38 (26.76%) RCTs described the method to generate the random sequence; only 6 RCTs had adequate allocation concealment; 24 (17.61%) RCTs mentioned “masking”, but only 7 described the process of masking. Three out of 40 items were reported clearly in all included trials, while five items were not mentioned at all. The quality of RCTs was low as assessed by the Jadad scale and 22 RCTs were high-quality research (≥3 points). Conclusions: The reporting quality of RCTs published in the five leading Chinese medical journals is low. Chinese journals should adopt the CONSORT statement to improve the reporting quality of Chinese randomized controlled trials. [Copyright &y& Elsevier]

Abstract: Objectives: We evaluated the usefulness of a simple run-in period to reduce drop-outs in a behavioral intervention to improve blood pressure (BP). In a pilot study where a run-in period was not used, we had a 25% drop-out rate. Methods: A prospective evaluation was performed in the context of a blinded 3-arm randomized trial. Participants are eligible if they have uncontrolled BP on 2 consecutive visits. Potential participants are approached during a routine visit, informed, consented and enrolled. After a 1-month run-in period during which all participants receive a phone call to: i) verify phone availability, ii) get basic information on treatment, and iii) confirm the baseline visit, participants return for a baseline visit. They are then randomized to one of the three treatment arms: usual care, non-tailored counseling, or tailored counseling. Participants make return visits at 3, 6 and 12 months. Results: Of the 1275 potential participants who received detailed study information, 301 consented to participate, of whom 226 were enrolled. During the run-in period, 73 withdrew consent and 153 participants were randomized; 7 subsequently dropped out. There were no differences (p >.1) between the 73 cancelled and the 153 randomized patients. There were fewer drop-outs than in the pilot study (5% vs. 25%, p <.0001). Conclusions: The run-in period reduces the number of drop-outs after randomization and improves statistical power. In order to retain external validity, it is important to compare participants who remain in the study and those that cancel, and incorporate that in generalizing from the study. [Copyright &y& Elsevier]

Post-traumatic stress disorder (PTSD), prevalent among Veterans, increases risk for having a high Body Mass Index. Although the Veterans Health Administration (VHA) offers an evidence-based behavioral weight management program called MOVE!, participants with PTSD lose less weight than those without mental health conditions, despite comparable participation. PTSD symptoms can interfere with one's ability to be physically active and maintain a healthy diet, the key targets in weight management programs. We developed and piloted a behavioral weight management program called MOVE! + UP that targets PTSD-related weight loss barriers. MOVE! + UP includes 16 group sessions with training in evidence-based weight management strategies, coupled with Cognitive Behavior Therapy (CBT) skills to address PTSD-specific barriers. The 16 sessions also include 30-min community walks to address PTSD-related barriers that may impede exercise. Two individual dietician sessions are provided. This hybrid type 1 randomized controlled trial (RCT) will compare MOVE! + UP to standard care—MOVE!—among 164 Veterans with BMI ≥ 25 who are receiving care for PTSD. We will randomize participants to MOVE! + UP or standard care and will compare absolute post-baseline change in weight at 6 (primary outcome) and 12 (secondary outcome) months, and PTSD symptom severity at 6 and 12 months (secondary outcome). Exploratory analyses will compare the treatment conditions on treatment targets measured at 6 months (e.g., physical activity, eating behavior, social support). Finally, we will estimate intervention costs, and identify MOVE! + UP implementation barriers and facilitators. If effective, MOVE! + UP could be an efficient way to simultaneously address physical and mental health for Veterans with PTSD. [ABSTRACT FROM AUTHOR]

Posttraumatic stress disorder (PTSD) can be a severe problem, affecting veterans and military personnel at higher rates than the general community. First-line treatment for PTSD, prolonged exposure (PE), is typically delivered weekly for 10–12 weeks, however this duration can pose a barrier to accessing and completing the treatment, particularly for current serving military. This paper presents the RESTORE trial protocol, the first randomized controlled trial of massed PE therapy outside of the United States and by an independent research group. One hundred and thirty-five Australian Defence Force members and veterans (18–80 years) who meet criteria for PTSD related to a military trauma will be randomly allocated to one of two conditions: standard PE (SPE; 10 weekly 90-min sessions) or massed PE (MPE; 10 daily 90-min sessions). Across eight sites, patients will be assessed at pre-treatment, and at 4 weeks, 12 weeks, and 12 months post-treatment commencement. The primary outcome is clinician-measured and self-reported PTSD symptom severity at the 12 week assessment. We hypothesize that MPE will be as effective as SPE in reducing PTSD severity at 12 weeks post-treatment commencement. The adaptation and testing of evidence-based interventions is critical to reduce barriers to treatment uptake among veterans and military personnel. Outcomes of this study have the potential to result in international, cross-service uptake and delivery of this rapid treatment for veterans and military members, as well as civilians, thereby improving clinical outcomes for patients and their families. [ABSTRACT FROM AUTHOR]

Survivors of head and neck cancer (HNC) can have multiple health concerns. To facilitate their care, we developed and pilot-tested a clinical informatics intervention, HN-STAR. HN-STAR elicits concerns online from HNC survivors prior to a routine oncology clinic visit. HN-STAR then presents tailored evidence-based clinical recommendations as a clinical decision support tool to be used during the visit where the oncology clinician and survivor select symptom management strategies and other actions. This generates a survivorship care plan (SCP). Online elicitation of health concerns occurs 3, 6, and 9 months after the clinic visit, generating an updated SCP each time. HN-STAR encompasses important methods of improving survivorship care (e.g., needs assessment, tailored interventions, dissemination of guidelines) and will be evaluated in a pragmatic trial to maximize external validity. This hybrid type 1 implementation-effectiveness trial tests HN-STAR effectiveness while studying barriers and facilitators to implementation in community oncology practices within the National Cancer Institute Community Oncology Research Program. Effectiveness will be measured as differences in key survivorship outcomes between HNC participants who do and do not use HN-STAR over one year after the clinic visit. The primary endpoint is HNC-specific quality of life; other outcomes include patient-centered measures and receipt of guideline-concordant care. Implementation outcomes will be assessed of survivors, providers, and clinic stakeholders. The hybrid design will provide insight into a dose-response relationship between the extent of implementation fidelity and effectiveness outcomes, as well as how to incorporate HN-STAR into standard practice outside the research setting. [ABSTRACT FROM AUTHOR]

Abstract: Hepatitis C (HCV)-related end stage liver disease is a primary cause of morbidity and mortality in people with HIV. Despite this, co-infected patients have low rates of HCV treatment initiation and completion. This is in large part due to the risk of pegylated-interferon alpha (PEG-IFN-α)-related neuropsychiatric complications. We describe the design of a multicentre randomized, placebo-controlled trial that evaluates whether antidepressant prophylaxis is superior to early detection and treatment of depression in increasing the successful completion of HCV therapy. Seventy-six HIV+ adults with chronic HCV infection requiring therapy and with no contraindications to PEG-IFN-α/ribavirin will be randomized in a 1:1 ratio to receive citalopram or placebo starting three weeks prior to HCV treatment. A novel aspect of the trial design is the built-in management of emergent depression while maintaining the blinded treatment assignment. This will permit the comparison of prophylactic versus therapeutic use of citalopram. The primary outcome is the average proportion of prescribed PEG-IFN-α and ribavirin doses taken per month at weeks 12 and 24, and will be compared between treatment arms. The study will also compare the development of moderate-to-severe depression between treatment arms. A unique feature of this trial will be the use of Telepsychiatry to standardize observer-administered neuropsychiatric evaluations. Assessments of anxiety, quality of life, and adherence to therapy, as well as pathogenetic studies of neuropsychiatric side effects, will be conducted. Intention-to-treat analyses using random regression modeling will be employed to analyze longitudinal data on prescribed PEG-IFN-α and ribavirin doses. Survival analyses will be used to compare the time to the development of depression between the two arms. Effective prevention of a broad range of neuropsychiatric symptoms by citalopram has the potential to diminish PEG-IFN-α associated morbidity and consequently, allow a greater number of patients to complete full therapy. [Copyright &y& Elsevier]

Abstract: Background: Sexually transmitted infection (STI) clinics provide an opportune setting for HIV prevention efforts. This randomized controlled trial evaluated a unique, two-step approach to sexual risk reduction at a publicly-funded STI clinic. Methods: During an initial visit, patients completed an audio-computer assisted self-interview (ACASI), were randomized to and received one of two brief interventions, obtained medical care, and completed a post-assessment. Next, two-thirds of the patients were assigned to attend an intensive sexual risk reduction workshop. At 3, 6, and 12 months, patients completed additional ACASIs and provided urine specimens to assess behavior change and incident STIs. Results: During a 28-month interval, 5613 patients were screened, 2691 were eligible, and 1483 consented to participate and were randomized; the modal reason for declining was lack of time (82%). Consenting patients included 688 women and 795 men; 64% of participants were African-American. The sample was low-income, with 57% reporting an annual income of less than $15,000; most participants (62%) had a high school education or less, and 51% were unemployed. Sexual risk behavior was common, as indicated by multiple sexual partners (mean=32.8, lifetime; mean=2.8, past 3 months), unprotected sex (mean=17.3 episodes, past 3 months), and prior STIs (mean=3.3, lifetime; 23% at baseline). Bivariate analyses confirmed our prediction that HIV-related motivation and behavioral skills would be related to current sexual risk behavior. All patients received a brief intervention; patient satisfaction ratings were uniformly high for both interventions (all means ≥3.7 on 4-point scales). Fifty-six percent of invited patients attended the intensive workshop, and attendance did not differ as a function of brief intervention. Patient satisfaction ratings were also uniformly positive for the workshop interventions (all means ≥3.6). Return to follow-up assessments exceeded 70%. Conclusions: Results demonstrate that implementing an HIV preventive program in a busy, public clinic is feasible and well-accepted by patients. Ongoing evaluation will determine if the interventions reduce sexual risk behavior and lower incident STIs. [Copyright &y& Elsevier]

Abstract: Background: Randomized controlled trials have provided unequivocal evidence that treatment of hypertension decreases mortality and major disability from cardiovascular disease; however, blood pressure remains inadequately treated in most affected individuals. This large gap continues despite the facts that more than 90% of adults with hypertension have health insurance, and hypertension is the leading cause of visits to the doctor. New approaches are needed to improve hypertension care. Objectives: The Electronic Communications and Home Blood Pressure Monitoring (e-BP) study is a three-arm randomized controlled trial designed to determine whether care based on the Chronic Care Model and delivered over the Internet improves hypertension care. The primary study outcomes are systolic, diastolic, and blood pressure control; secondary outcomes are medication adherence, patient self-efficacy, satisfaction and quality of life, and healthcare utilization and costs. Methods: Hypertensive patients receiving care at Group Health medical centers are eligible if they have uncontrolled blood pressure on two screening visits and access to the Web and an e-mail address. Study participants are randomly assigned to three intervention groups: (a) usual care; (b) home blood pressure monitoring receipt and proficiency training on its use and the Group Health secure patient website (with secure e-mail access to their healthcare provider, access to a shared medical record, prescription refill and other services); or (c) this plus pharmacist care management (collaborative care management between the patient, the pharmacist, and the patient''s physician via a secure patient website and the electronic medical record). Conclusion: We will determine whether a new model of patient-centered care that leverages Web communications, self-monitoring, and collaborative care management improves hypertension control. If this model proves successful and cost-effective, similar interventions could be used to improve the care of large numbers of patients with uncontrolled hypertension. [Copyright &y& Elsevier]