The randomized placebo-phase design: Evaluation, interim monitoring and analysis

The randomized placebo-phase design, also known as the randomized delayed-start design, has been proposed as an approach to circumvent the reluctance of patients and physicians to participate in trials with a placebo control. Although there is some practical appeal to the design and it has been used in an increasing number of active and ongoing trials, there are often overlooked issues relative to statistical power, estimating sample size and determining plans for interim analysis that may limit its usefulness. We developed a general model for describing the pattern of treatment response and based on the specified parameters of this model, derive and compare different strategies for interim monitoring. In addition to statistical power considerations, we also provide results from extensive simulations investigating the robustness of the proposed procedures since the efficiency of the randomized placebo-phase design is highly dependent on the assumptions made about the form of the alternative hypotheses. Public Health Relevance: The randomized clinical trial is the gold standard for evaluating new medical treatments/public health interventions. Indiscriminate use of the RPPD may result in failure to identify important new treatment/interventions because of low statistical power

Subjective Estimation of Physical Activity Using the IPAQ Varies by Fitness Level

Background: Subjective measures of moderate and vigorous physical activity (MVPA) rely on ‘relative’ intensity while objective measures capture ‘absolute’ intensity, thus fit individuals may perceive the same activity differently than unfit individuals. Methods: Adults (N=211) wore the SenseWear Armband (SWA) for ten consecutive days to objectively assess sedentary time and MVPA. On day eight participants completed the International Physical Activity Questionnaire (IPAQ) to subjectively assess sitting time and MVPA. Fitness was assessed via a maximal treadmill test, and participants were classified as ’unfit’ if the result was in the bottom tertile of the study population by sex or ‘fit’ if in the upper two tertiles. Results: Overall, estimates of MVPA between the IPAQ and SWA were not significantly different (IPAQ minus SWA, 67.4±919.1 MVPA minutes/week, P=.29). However, unfit participants overestimated MVPA using the IPAQ by 37.3% (P=.02), but fit participants did not (P=.99). This between-group difference was due to overestimation using the IPAQ of moderate activity by 93.8 minutes/week among the unfit individuals, but underestimation of moderate activity among the fit participants by 149.4 minutes/week. Conclusion: Subjective measures of MVPA using the IPAQ varied by fitness category, with unfit participants overestimating their MVPA and fit participants accurately estimating their MVPA

The Association Between Sedentary Behaviors During Weekdays and Weekend with Change in Body Composition in Young Adults

Background: High sedentary time has been considered an important chronic disease risk factor but there is only limited information on the association of specific sedentary behaviors on weekdays and weekend-days with body composition. The present study examines the prospective association of total sedentary time and specific sedentary behaviors during weekdays and the weekend with body composition in young adults. Methods: A total of 332 adults (50% male; 27.7 ±3.7 years) were followed over a period of 1 year. Time spent sedentary, excluding sleep (SED), and in physical activity (PA) during weekdays and weekend-days was objectively assessed every 3 months with a multisensor device over a period of at least 8 days. In addition, participants reported sitting time, TV time and non-work related time spent at the computer separately for weekdays and the weekend. Fat mass and fat free mass were assessed via dual x-ray absorptiometry and used to calculate percent body fat (%BF). Energy intake was estimated based on TDEE and change in body composition. Results: Cross-sectional analyses showed a significant correlation between SED and body composition (0.18 ≤ r ≤ 0.34). Associations between body weight and specific sedentary behaviors were less pronounced and significant during weekdays only (r ≤ 0.16). Nevertheless, decrease in SED during weekends, rather than during weekdays, was significantly associated with subsequent decrease in %BF (β = 0.06, p \u3c0.01). After adjusting for PA and energy intake, results for SED were no longer significant. Only the association between change in sitting time during weekends and subsequent %BF was independent from change in PA or energy intake (β%BF = 0.04, p = 0.01), while there was no significant association between TV or computer time and subsequent body composition. Conclusions: The stronger AIMS Public Health Volume 3, Issue 2, 375-388. prospective association between sedentary behavior during weekends with subsequent body composition emphasizes the importance of leisure time behavior in weight management

The Association of Physical Activity during Weekdays and Weekend with Body Composition in Young Adults

Physical activity (PA) is a key contributor in long-term weight management but there remains limited research on the association between weekly PA patterns and weight change. The purpose of the present study was to examine the prospective association between weekly PA patterns and weight change in generally healthy young adults. Anthropometric measurements, including dual X-ray absorptiometry, were obtained every 3 months over a period of one year in 338 adults (53% male). At each measurement time, participants wore a multisensor device for a minimum of 10 days to determine total daily energy expenditure and time spent sleeping, sedentary, in light PA (LPA), in moderate PA (MPA), and in vigorous PA (VPA). PA did not differ between weekdays and the weekend at baseline. Twenty-four-hour sleep time, however, was significantly longer during weekends compared to weekdays, which was associated with less time spent sedentary. Weight loss was associated with a significant increase in LPA at the expense of sedentary time during the weekend but not during weekdays. Regression analyses further revealed an inverse association between change in VPA during the weekend and body composition at 12-month follow-up. Taken together, these results suggest that weekend PA plays an important role in long-term weight management

The Association of Physical Activity during Weekdays and Weekend with Body Composition in Young Adults

Physical activity (PA) is a key contributor in long-term weight management but there remains limited research on the association between weekly PA patterns and weight change. The purpose of the present study was to examine the prospective association between weekly PA patterns and weight change in generally healthy young adults. Anthropometric measurements, including dual X-ray absorptiometry, were obtained every 3 months over a period of one year in 338 adults (53% male). At each measurement time, participants wore a multisensor device for a minimum of 10 days to determine total daily energy expenditure and time spent sleeping, sedentary, in light PA (LPA), in moderate PA (MPA), and in vigorous PA (VPA). PA did not differ between weekdays and the weekend at baseline. Twenty-four-hour sleep time, however, was significantly longer during weekends compared to weekdays, which was associated with less time spent sedentary. Weight loss was associated with a significant increase in LPA at the expense of sedentary time during the weekend but not during weekdays. Regression analyses further revealed an inverse association between change in VPA during the weekend and body composition at 12-month follow-up. Taken together, these results suggest that weekend PA plays an important role in long-term weight management

The Association Between Sedentary Behaviors During Weekdays and Weekend with Change in Body Composition in Young Adults

Background: High sedentary time has been considered an important chronic disease risk factor but there is only limited information on the association of specific sedentary behaviors on weekdays and weekend-days with body composition. The present study examines the prospective association of total sedentary time and specific sedentary behaviors during weekdays and the weekend with body composition in young adults. Methods: A total of 332 adults (50% male; 27.7 ±3.7 years) were followed over a period of 1 year. Time spent sedentary, excluding sleep (SED), and in physical activity (PA) during weekdays and weekend-days was objectively assessed every 3 months with a multisensor device over a period of at least 8 days. In addition, participants reported sitting time, TV time and non-work related time spent at the computer separately for weekdays and the weekend. Fat mass and fat free mass were assessed via dual x-ray absorptiometry and used to calculate percent body fat (%BF). Energy intake was estimated based on TDEE and change in body composition. Results: Cross-sectional analyses showed a significant correlation between SED and body composition (0.18 ≤ r ≤ 0.34). Associations between body weight and specific sedentary behaviors were less pronounced and significant during weekdays only (r ≤ 0.16). Nevertheless, decrease in SED during weekends, rather than during weekdays, was significantly associated with subsequent decrease in %BF (β = 0.06, p \u3c0.01). After adjusting for PA and energy intake, results for SED were no longer significant. Only the association between change in sitting time during weekends and subsequent %BF was independent from change in PA or energy intake (β%BF = 0.04, p = 0.01), while there was no significant association between TV or computer time and subsequent body composition. Conclusions: The stronger AIMS Public Health Volume 3, Issue 2, 375-388. prospective association between sedentary behavior during weekends with subsequent body composition emphasizes the importance of leisure time behavior in weight management

Cross-sectional and longitudinal associations between different exercise types and food cravings in free-living healthy young adults

Introduction: An increase in energy intake due to alterations in hedonic appetite sensations may, at least in part, contribute to lower-than-expected weight loss in exercise interventions. The aim of this study was to examine cross-sectional and longitudinal associations between habitual exercise participation and food cravings in free-living young adults. Methods: A total of 417 adults (49% male, 28 ± 4 years) reported frequency and duration of walking, aerobic exercise, resistance exercise and other exercise at baseline and every 3 months over a 12-month period. Food cravings were assessed via the Control of Eating Questionnaire at baseline and 12-month follow-up. Results: Cross-sectional analyses revealed more frequent cravings for chocolate and a greater difficulty to resist food cravings in women compared to men (p < 0.01). Only with resistance exercise significant sex by exercise interaction effects were observed with favorable responses in men but not in women. Significant main effects were shown for walking and aerobic exercise with exercisers reporting more frequent food cravings for chocolate and fruits and greater difficulty to resist eating compared to non-exercisers (p < 0.05). Longitudinal analyses revealed significant interaction effects for other exercise (p < 0.05) with favorable results in men but not women. Furthermore, significant main effects were observed for aerobic exercise, resistance exercise and total exercise with an increase in exercise being associated with a reduced difficulty to resist food cravings (p < 0.05). Discussion: The association between exercise participation and hedonic appetite sensations varies by exercise type and sex. Even though exercise was associated with more frequent and greater difficulty to food cravings in the cross-sectional analyses, which may be attributed to greater energy demands, longitudinal results indicate beneficial effects of increased exercise on appetite control, particularly in men

Subcortical brain volume, regional cortical thickness, and cortical surface area across disorders: findings from the ENIGMA ADHD, ASD, and OCD Working Groups

Objective Attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. We aimed to directly compare all three disorders. The ENIGMA consortium is ideally positioned to investigate structural brain alterations across these disorders. Methods Structural T1-weighted whole-brain MRI of controls (n=5,827) and patients with ADHD (n=2,271), ASD (n=1,777), and OCD (n=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. We examined subcortical volume, cortical thickness and surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults using linear mixed-effects models adjusting for age, sex and site (and ICV for subcortical and surface area measures). Results We found no shared alterations among all three disorders, while shared alterations between any two disorders did not survive multiple comparisons correction. Children with ADHD compared to those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller ICV than controls and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared to adult controls and other clinical groups. No OCD-specific alterations across different age-groups and surface area alterations among all disorders in childhood and adulthood were observed. Conclusion Our findings suggest robust but subtle alterations across different age-groups among ADHD, ASD, and OCD. ADHD-specific ICV and hippocampal alterations in children and adolescents, and ASD-specific cortical thickness alterations in the frontal cortex in adults support previous work emphasizing neurodevelopmental alterations in these disorders