First-in-Human, Phase I Dose-Escalation and Dose-Expansion Study of Trophoblast Cell-Surface Antigen 2-Directed Antibody-Drug Conjugate Datopotamab Deruxtecan in Non-Small-Cell Lung Cancer: TROPION-PanTumor01.

PURPOSE: This first-in-human, dose-escalation and dose-expansion study evaluated the safety, tolerability, and antitumor activity of datopotamab deruxtecan (Dato-DXd), a novel trophoblast cell-surface antigen 2 (TROP2)-directed antibody-drug conjugate in solid tumors, including advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Adults with locally advanced/metastatic NSCLC received 0.27-10 mg/kg Dato-DXd once every 3 weeks during escalation or 4, 6, or 8 mg/kg Dato-DXd once every 3 weeks during expansion. Primary end points were safety and tolerability. Secondary end points included objective response rate (ORR), survival, and pharmacokinetics. RESULTS: Two hundred ten patients received Dato-DXd, including 180 in the 4-8 mg/kg dose-expansion cohorts. This population had a median of three prior lines of therapy. The maximum tolerated dose was 8 mg/kg once every 3 weeks; the recommended dose for further development was 6 mg/kg once every 3 weeks. In patients receiving 6 mg/kg (n = 50), median duration on study, including follow-up, and median exposure were 13.3 and 3.5 months, respectively. The most frequent any-grade treatment-emergent adverse events (TEAEs) were nausea (64%), stomatitis (60%), and alopecia (42%). Grade ≥3 TEAEs and treatment-related AEs occurred in 54% and 26% of patients, respectively. Interstitial lung disease adjudicated as drug-related (two grade 2 and one grade 4) occurred in three of 50 patients (6%). The ORR was 26% (95% CI, 14.6 to 40.3), and median duration of response was 10.5 months; median progression-free survival and overall survival were 6.9 months (95% CI, 2.7 to 8.8 months) and 11.4 months (95% CI, 7.1 to 20.6 months), respectively. Responses occurred regardless of TROP2 expression. CONCLUSION: Promising antitumor activity and a manageable safety profile were seen with Dato-DXd in heavily pretreated patients with advanced NSCLC. Further investigation as first-line combination therapy in advanced NSCLC and as monotherapy in the second-line setting and beyond is ongoing.

The Resistance Exercise in Already Active Diabetic Individuals (READI) Randomized Clinical Trial.

CONTEXT: Resistance exercise training (strength training) and aerobic exercise training are both recommended for people with type 1 diabetes, but it is unknown whether adding resistance exercise provides incremental benefits in people with this condition who already perform aerobic exercise regularly. OBJECTIVE: This work aimed to evaluate the incremental effect of resistance training on glycated hemoglobin A1c (HbA1c), fitness, body composition, and cardiometabolic risk factors in aerobically active people with type 1 diabetes. METHODS: The Resistance Exercise in Already-active Diabetic Individuals (READI) trial (NCT00410436) was a 4-center, randomized, parallel-group trial. After a 5-week run-in period with diabetes management optimization, 131 aerobically active individuals with type 1 diabetes were randomly assigned to resistance exercise (n = 71, intervention-INT) or control (n = 60, CON) for 22 additional weeks. Both groups maintained their aerobic activities and were provided dietary counseling throughout. Exercise training was 3 times per week at community-based facilities. The primary outcome was HbA1c, and secondary outcomes included fitness (peak oxygen consumption, muscle strength), body composition (anthropometrics, dual-energy x-ray absorptiometry, computed tomography), and cardiometabolic risk markers (lipids, apolipoproteins). Assessors were blinded to group allocation. RESULTS: There were no significant differences in HbA1c change between INT and CON. Declines in HbA1c (INT: 7.75 ± 0.10% [61.2 ± 1.1 mmol/mol] to 7.55 ± 0.10% [59 ± 1.1 mmol/mol]; CON: 7.70 ± 0.11% [60.7 ± 1.2 mmol/mol] to 7.57 ± 0.11% [59.6 ± 1.3 mmol/mol]; intergroup difference in change -0.07 [95% CI, -0.31 to 0.18]). Waist circumference decreased more in INT than CON after 6 months (P = .02). Muscular strength increased more in INT than in CON (P < .001). There were no intergroup differences in hypoglycemia or any other variables. CONCLUSION: Adding resistance training did not affect glycemia, but it increased strength and reduced waist circumference, in aerobically active individuals with type 1 diabetes.

Management of Adverse Events in Early Clinical Trials by Advanced Practice Providers in the Outpatient Setting: The University of Texas MD Anderson Cancer Center Experience.

Background: Advanced practice providers (APPs) play important roles in enrolling, educating, and caring for patients in clinical trials. However, much remains unknown about the role of APPs in managing adverse events (AEs) in early (phase I to II) clinical trials. In this study, we assessed the outpatient management of grade 3 to 4 AEs by APPs in early trials and characterized the workflow of our APP Phase I to II Fast Track (FT) Clinic. Patients and Methods: We retrospectively reviewed records of patients with advanced or metastatic solid tumors enrolled in phase I to II clinical trials who were seen by APPs from September 2017 to August 2018 in the APP phase I to II FT clinic in the Department of Investigational Cancer Therapeutics. Results: A total of 808 patients enrolled in 159 clinical trials were seen in 2,697 visits (median 3 visits per patient; range 1-28) by 10 APPs. Treatment was interrupted in 6.9% of visits, and grade 3 to 4 AEs were seen in 5.4% of visits; however, patients from 1.4% of visits were sent to the emergency center (EC) and/or admitted. Patients referred to the EC and/or admitted were more likely to have baseline hypoalbuminemia, high lactate dehydrogenase, and poor Eastern Cooperative Oncology Group performance status (i.e., ECOG > 1; p < .001). There were no associations between EC referral and gender, APP years of experience, or type of treatment. Conclusions: The APP Phase I to II FT Clinic has an important role in the management of AEs by APPs in early clinical trials in the outpatient setting, potentially avoiding EC visits and admissions.

Risk for Recurrent Venous Thromboembolism in Patients With Subsegmental Pulmonary Embolism Managed Without Anticoagulation : A Multicenter Prospective Cohort Study.

BACKGROUND: The incidence of pulmonary embolism has been increasing, but its case-fatality rate is decreasing, suggesting a lesser severity of illness. The clinical importance of patients with pulmonary embolism isolated to the subsegmental vessels is unknown. OBJECTIVE: To determine the rate of recurrent venous thromboembolism in patients with subsegmental pulmonary embolism managed without anticoagulation. DESIGN: Multicenter prospective cohort study. (ClinicalTrials.gov: NCT01455818). SETTING: Eighteen sites between February 2011 and February 2021. PATIENTS: Patients with isolated subsegmental pulmonary embolism. INTERVENTION: At diagnosis, patients underwent bilateral lower-extremity venous ultrasonography, which was repeated 1 week later if results were negative. Patients without deep venous thrombosis did not receive anticoagulant therapy. MEASUREMENTS: The primary outcome was recurrent venous thromboembolism during the 90-day follow-up period. RESULTS: Recruitment was stopped prematurely because the predefined stopping rule was met after 292 of a projected 300 patients were enrolled. Of the 266 patients included in the primary analysis, the primary outcome occurred in 8 patients, for a cumulative incidence of 3.1% (95% CI, 1.6% to 6.1%) over the 90-day follow-up. The incidence of recurrent venous thromboembolism was 2.1% (CI, 0.8% to 5.5%) and 5.7% (CI, 2.2% to 14.4%) over the 90-day follow-up in patients with single and multiple isolated subsegmental pulmonary embolism, respectively. No patients had a fatal recurrent pulmonary embolism. LIMITATION: The study was restricted to patients with low-risk subsegmental pulmonary embolism. CONCLUSION: Overall, patients with subsegmental pulmonary embolism who did not have proximal deep venous thrombosis had a higher-than-expected rate of recurrent venous thromboembolism. PRIMARY FUNDING SOURCE: Heart and Stroke Foundation of Canada and French Ministry of Health Programme Hospitalier de Recherche Clinique.

Patient-Reported Out-of-Pocket Costs and Financial Toxicity During Early-Phase Oncology Clinical Trials.

BACKGROUND: Clinical trials are an important therapeutic option for patients with cancer. Although financial burden in cancer treatment is well documented, the financial burden associated with clinical trials is not well understood. PATIENTS AND METHODS: We conducted a survey regarding economic burden and financial toxicity in patients with cancer enrolled in phase I clinical trials for >1 month. Financial toxicity score was assessed using the Comprehensive Score for Financial Toxicity survey. Patients also reported monthly out-of-pocket (OOP) costs. RESULTS: Two hundred and thirteen patients completed the survey (72% non-Hispanic White; 45% with annual income ≤$60,000; 50% lived >300 miles from the clinic; 37% required air travel). Forty-eight percent of patients had monthly OOP costs of at least $1,000. Fifty-five percent and 64% of patients reported unanticipated medical and nonmedical expenses, respectively. Worse financial toxicity was associated with yearly household income <$60,000 (odds ratio [OR]: 2.7; p = .008), having unanticipated medical costs (OR: 3.2; p = .024), and living >100 miles away from the clinical trial hospital (OR: 2.3; p = .043). Non-White or Hispanic patients (OR: 2.5; p = .011) and patients who were unemployed or not working outside the home (OR: 2.5; p = .016) were more likely to report high unanticipated medical costs. CONCLUSION: Among patients with cancer participating in clinical trials, economic burden is high, and most of patients' OOP costs were nonmedical costs. Financial toxicity is disproportionally higher in patients with lower income and those who travel farther, and unexpected medical costs were more common among non-White or Hispanic patients. OOP costs can be substantial and are often unexpected for patients. IMPLICATIONS FOR PRACTICE: The financial burden of cancer treatment is well documented, but there are limited data regarding the financial burden associated with cancer clinical trials. This study surveyed 213 patients enrolled in early-phase clinical trials. Monthly out-of-pocket costs were at least $1000 for nearly half of patients. Worse financial toxicity was associated with income <$60,000 and living farther away from the hospital. Racial/ethnic minorities had higher rates of unanticipated medical costs. These data help to quantify the high financial burden for patients and may reveal a cause of disparities in clinical trial enrollment for underrepresented populations.

Elevated serum interleukin-8 is associated with enhanced intratumor neutrophils and reduced clinical benefit of immune-checkpoint inhibitors.

Serum interleukin-8 (IL-8) levels and tumor neutrophil infiltration are associated with worse prognosis in advanced cancers. Here, using a large-scale retrospective analysis, we show that elevated baseline serum IL-8 levels are associated with poor outcome in patients (n = 1,344) with advanced cancers treated with nivolumab and/or ipilimumab, everolimus or docetaxel in phase 3 clinical trials, revealing the importance of assessing serum IL-8 levels in identifying unfavorable tumor immunobiology and as an independent biomarker in patients receiving immune-checkpoint inhibitors.

Does exercise training affect resting metabolic rate in adolescents with obesity?

We evaluated the hypothesis that resistance exercise training performed alone or in combination with aerobic exercise training would increase resting metabolic rate (RMR) relative to aerobic-only and nonexercising control groups. Postpubertal adolescents (N = 304) aged 14-18 years with obesity (body mass index (BMI) ≥ 95th percentile) or overweight (BMI ≥ 85th percentile + additional diabetes risk factor(s)) were randomized to 4 groups for 22 weeks: Aerobic exercise training, Resistance exercise training, Combined aerobic and resistance exercise training, or Control. All participants received dietary counselling targeting a daily energy deficit of 250 kcal. RMR was measured by indirect calorimetry and body composition by magnetic resonance imaging. There was no significant change in RMR in any group, in spite of significant within-group increases in fat-free mass in the Aerobic, Resistance, and Combined exercise training groups. RMR at baseline and 6 months were Aerobic: 1972 ± 38 and 1990 ± 41; Resistance: 2024 ± 37 and 1992 ± 41; Combined: 2023 ± 38 and 1995 ± 38; Control: 2075 ± 38 and 2073 ± 39 kcal/day (p > 0.05). There were no between-group differences in RMR after adjustment for total body weight or fat-free mass between groups over time. Per-protocol analyses including only participants with ≥70% adherence, and analyses stratified by sex, also showed no within- or between-group differences in RMR. In conclusion, despite an increase in fat-free mass in all exercise groups, 6 months of aerobic, resistance, or combined training with modest dietary restriction did not increase RMR compared with diet only in adolescents with obesity.

Body composition and energy intake - skeletal muscle mass is the strongest predictor of food intake in obese adolescents: The HEARTY trial.

There has been renewed interest in examining the relationship between specific components of energy expenditure and the overall influence on energy intake (EI). The purpose of this cross-sectional analysis was to determine the strongest metabolic and anthropometric predictors of EI. It was hypothesized that resting metabolic rate (RMR) and skeletal muscle mass would be the strongest predictors of EI in a sample of overweight and obese adolescents. 304 post-pubertal adolescents (91 boys, 213 girls) aged 16.1 (±1.4) years with body mass index at or above the 95th percentile for age and sex OR at or above the 85th percentile plus an additional diabetes risk factor were measured for body weight, RMR (kcal/day) by indirect calorimetry, body composition by magnetic resonance imaging (fat free mass (FFM), skeletal muscle mass, fat mass (FM), and percentage body fat), and EI (kcal/day) using 3 day food records. Body weight, RMR, FFM, skeletal muscle mass, and FM were all significantly correlated with EI (p < 0.005). After adjusting the model for age, sex, height, and physical activity, only FFM (ß = 21.9, p = 0.007) and skeletal muscle mass (ß = 25.8, p = 0.02) remained as significant predictors of EI. FFM and skeletal muscle mass also predicted dietary protein and fat intake (p < 0.05), but not carbohydrate intake. In conclusion, with skeletal muscle mass being the best predictor of EI, our results support the hypothesis that the magnitude of the body's lean tissue is related to absolute levels of EI in a sample of inactive adolescents with obesity.

Screen time is associated with depressive symptomatology among obese adolescents: a HEARTY study.

UNLABELLED: Obese adolescents spend a disproportionate time in screen-based activities and are at higher risk for clinical depression compared to their normal-weight peers. While screen time is associated with obesity and cardiometabolic risk factors, little is known about the relationship between screen time and mental health. This cross-sectional study examines the association between duration and types of screen time and depressive symptomatology (subclinical symptoms) in a sample of 358 (261 female; 97 male) overweight and obese adolescents aged 14-18 years. Self-report measures assessed depressive symptoms and time spent in different types of screen behavior (TV, recreational computer use, and video games). After controlling for age, ethnicity, sex, parental education, body mass index (BMI), physical activity, caloric intake, carbohydrate intake, and intake of sugar-sweetened beverages, total screen time was significantly associated with more severe depressive symptomatology (ß = 0.21, p = 0.001). After adjustment, time spent playing video games (ß = 0.13, p = 0.05) and recreational computer time (ß = 0.18, p = 0.006) was associated with depressive symptoms, but TV viewing was not. CONCLUSIONS: Screen time may represent a risk factor or marker of depressive symptomatology in obese adolescents. Future intervention research should evaluate whether reducing screen exposure reduces depressive symptoms in obese youth, a population at increased risk for psychological disorders. WHAT IS KNOWN: • Screen time is associated with an increased risk of obesity in youth. • Screen time is associated with an adverse cardio-metabolic profile in youth. What is New: • Screen time is associated with more severe depressive symptoms in overweight and obese adolescents. • Time spent in recreational computer use and playing video games, but not TV viewing, was associated with more severe depressive symptoms in overweight and obese adolescents.

Effects of aerobic training, resistance training, or both on cardiorespiratory and musculoskeletal fitness in adolescents with obesity: the HEARTY trial.

The purpose of this study was to examine the effects of aerobic, resistance, and combined exercise training on cardiorespiratory and musculoskeletal fitness in postpubertal adolescents with obesity. After a 4-week supervised moderate-intensity exercise run-in, 304 adolescents aged 14-18 years with body mass index ≥85th percentile were randomized to 4 groups for 22 weeks of aerobic training, resistance training, combined training, or a nonexercising control. All participants received dietary counselling with a maximum daily energy deficit of 250 kcal. Cardiorespiratory fitness (peak oxygen consumption) was measured by indirect calorimetry using a graded treadmill exercise test. Musculoskeletal fitness was measured using the 2003 Canadian Physical Activity Fitness and Lifestyle Appraisal tests (hand grip, push-ups, partial curl-ups, sit and reach, and vertical jump). Muscular strength was assessed using an 8-repetition maximum test on the bench press, seated row, and leg press machines. A greater increase in peak oxygen consumption in the aerobic exercise group (30.6 ± 0.6 to 33.4 ± 0.7 mLO2/kg/min) was measured relative to the control group (30.6 ± 0.5 to 30.9 ± 0.7 mLO2/kg/min) (p = 0.002). Similarly, the number of partial curl-ups increased in the aerobic group (19 ± 1 to 23 ± 1) while no differences were measured in the control group (19 ± 1 to 20 ± 1) (p = 0.015). Increases in muscular strength and number of push-ups were greatest in the resistance group versus the control and combined groups versus the aerobic group (p < 0.05). In conclusion, aerobic training had the strongest effect on cardiorespiratory fitness, while resistance and combined training improved both muscular strength and endurance more than control and aerobic training alone, respectively, in adolescents with obesity.

Effects of aerobic training, resistance training, or both on psychological health in adolescents with obesity: The HEARTY randomized controlled trial.

OBJECTIVE: To determine the effects of aerobic training, resistance training, and combined training on mood, body image, and self-esteem in adolescents with obesity. METHOD: After a 4-week prerandomization treatment, 304 postpubertal adolescents (91 males, 213 females) with obesity ages 14-18 years were randomized to 1 of 4 groups for 22 weeks: aerobic training (n = 75), resistance training (n = 78), combined aerobic and resistance training (n = 75), or nonexercising control (n = 76). All participants received dietary counseling, with a daily energy deficit of 250 kcal. Mood was measured using the Brunel Mood Scale. Body image was assessed using the Multiple Body Self-Relations Questionnaire, and physical self-perceptions and global self-esteem were measured using the Harter Physical Self-Perceptions Questionnaire. RESULTS: Median adherence was 62%, 56%, and 64% in aerobic, resistance, and combined training, respectively. Resistance and combined training produced greater improvements than control on vigor, and resistance training reduced depressive symptoms. All groups improved on body image and physical self-perceptions, but combined showed greater increases than control on perceived physical conditioning, while only resistance training showed greater increases than controls on global self-esteem. Both combined and resistance training demonstrated greater increases in perceived strength than control. Psychological benefits were more related to better adherence and reductions in body fat than changes in strength or fitness. CONCLUSION: Resistance training, alone or in combination with aerobic training, may provide psychological benefits in adolescents with overweight or obesity, and therefore could be an alternative to aerobic training for some individuals in the biological and psychological management of adolescent obesity.

Screen time is independently associated with health-related quality of life in overweight and obese adolescents.

AIM: Excessive screen time and diminished health-related quality of life (HRQoL) are greater problems for obese than nonobese adolescents, but no research has examined the relationship between these two variables. This study examined the association between screen time and HRQoL in overweight and obese adolescents. METHODS: A sample of 358 overweight and obese adolescents aged 14-18 years were assessed at baseline between 2005 and 2010 as part of the Canadian Healthy Eating, Aerobic and Resistance Training in Youth (HEARTY) trial. We used the Pediatric Quality of Life (PEDS-QL) and other self-report measures to assess HRQoL and screen time, defined as how long the 261 females and 97 males spent viewing TV, using the computer and playing video games. RESULTS: After adjusting for socio-demographic variables, adiposity, physical activity and diet, screen time duration was associated with reduced overall HRQoL (adjusted r = -0.16, ß = -0.16, p = 0.009) and psychosocial HRQoL (adjusted r = -0.16, ß = -0.18, p = 0.004), but not physical HRQoL. No differences were found between males and females. CONCLUSION: Screen time was associated with reduced overall and psychosocial HRQoL in overweight and obese adolescents. Future research should determine whether reducing screen time improves overall and psychosocial HRQoL in obese adolescents.

Resistance Exercise in Already-Active Diabetic Individuals (READI): study rationale, design and methods for a randomized controlled trial of resistance and aerobic exercise in type 1 diabetes.

The Resistance Exercise in Already Active Diabetic Individuals (READI) trial aimed to examine whether adding a 6-month resistance training program would improve glycemic control (as reflected in reduced HbA1c) in individuals with type 1 diabetes who were already engaged in aerobic exercise compared to aerobic training alone. After a 5-week run-in period including optimization of diabetes care and low-intensity exercise, 131 physically active adults with type 1 diabetes were randomized to two groups for 22weeks: resistance training three times weekly, or waiting-list control. Both groups maintained the same volume, duration and intensity of aerobic exercise throughout the study as they did at baseline. HbA1c, body composition, frequency of hypoglycemia, lipids, blood pressure, apolipoproteins B and A-1 (ApoB and ApoA1), the ApoB-ApoA1 ratio, urinary albumin excretion, serum C-reactive protein, free fatty acids, total daily insulin dose, health-related quality of life, cardiorespiratory fitness and musculoskeletal fitness were recorded at baseline, 3 (for some variables), and 6 months. To our knowledge, READI is the only trial to date assessing the incremental health-related impact of adding resistance training for individuals with type 1 diabetes who are already aerobically active. Few exercise trials have been completed in this population, and even fewer have assessed resistance exercise. With recent improvements in the quality of diabetes care, the READI study will provide conclusive evidence to support or refute a major clinically relevant effect of exercise type in the recommendations for physical activity in patients with type 1 diabetes.

Low-molecular-weight heparin to prevent postpartum venous thromboembolism. A pilot randomised placebo-controlled trial.

The risk of venous thromboembolism (VTE) is elevated in the postpartum period. Low-molecular-weight heparin (LMWH) reduces the risk of VTE in many settings but is costly, inconvenient and increases bleeding. Randomised controlled trials (RCT) are required to determine if LMWH prophylaxis provides a clinical benefit in high-risk postpartum women. We sought to determine if a placebo-controlled RCT was feasible. We conducted a multi-national, double-blind pilot RCT in "high risk" postpartum women comparing 21 days of prophylactic dose LMWH to identical saline placebo injections. The primary pilot outcome was mean number of recruited women per centre per month. The planned primary outcome for the full trial was symptomatic objectively confirmed VTE or asymptomatic proximal deep-vein thrombosis diagnosed by a screening bilateral leg vein ultrasound at day 21. In six centres, a total of 1,346 potentially eligible women were approached to participate; 968 were ineligible, leaving 378 (31.5%) eligible patients. Of these, only 25 (6.6%) were randomised at a rate of 0.7 per centre per month. The primary reasons for declining participation were to avoid study injections and being too overwhelmed to participate in research. None of the participants had a VTE during follow-up. In conclusion, despite an adequate number of eligible participants, our double-blind RCT design was not feasible due to a very low consent rate. Other experimental approaches may be necessary to generate evidence in this important area of research.

Effects of aerobic training, resistance training, or both on percentage body fat and cardiometabolic risk markers in obese adolescents: the healthy eating aerobic and resistance training in youth randomized clinical trial.

IMPORTANCE: Little evidence exists on which exercise modality is optimal for obese adolescents. OBJECTIVE: To determine the effects of aerobic training, resistance training, and combined training on percentage body fat in overweight and obese adolescents. DESIGN, SETTING, AND PARTICIPANTS: Randomized, parallel-group clinical trial at community-based exercise facilities in Ottawa (Ontario) and Gatineau (Quebec), Canada, among previously inactive postpubertal adolescents aged 14 to 18 years (Tanner stage IV or V) with body mass index at or above the 95th percentile for age and sex or at or above the 85th percentile plus an additional diabetes mellitus or cardiovascular risk factor. INTERVENTIONS: After a 4-week run-in period, 304 participants were randomized to the following 4 groups for 22 weeks: aerobic training (n = 75), resistance training (n = 78), combined aerobic and resistance training (n = 75), or nonexercising control (n = 76). All participants received dietary counseling, with a daily energy deficit of 250 kcal. MAIN OUTCOMES AND MEASURES: The primary outcome was percentage body fat measured by magnetic resonance imaging at baseline and 6 months. We hypothesized that aerobic training and resistance training would each yield greater decreases than the control and that combined training would cause greater decreases than aerobic or resistance training alone. RESULTS: Decreases in percentage body fat were -0.3 (95% CI, -0.9 to 0.3) in the control group, -1.1 (95% CI, -1.7 to -0.5) in the aerobic training group (P = .06 vs controls), and -1.6 (95% CI, -2.2 to -1.0) in the resistance training group (P = .002 vs controls). The -1.4 (95% CI, -2.0 to -0.8) decrease in the combined training group did not differ significantly from that in the aerobic or resistance training group. Waist circumference changes were -0.2 (95% CI, -1.7 to 1.2) cm in the control group, -3.0 (95% CI, -4.4 to -1.6) cm in the aerobic group (P = .006 vs controls), -2.2 (95% CI -3.7 to -0.8) cm in the resistance training group (P = .048 vs controls), and -4.1 (95% CI, -5.5 to -2.7) cm in the combined training group. In per-protocol analyses (≥ 70% adherence), the combined training group had greater changes in percentage body fat (-2.4, 95% CI, -3.2 to -1.6) vs the aerobic group (-1.2; 95% CI, -2.0 to -0.5; P = .04 vs the combined group) but not the resistance group (-1.6; 95% CI, -2.5 to -0.8). CONCLUSIONS AND RELEVANCE: Aerobic, resistance, and combined training reduced total body fat and waist circumference in obese adolescents. In more adherent participants, combined training may cause greater decreases than aerobic or resistance training alone. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00195858.

Screen viewing and diabetes risk factors in overweight and obese adolescents.

BACKGROUND: Sedentary behavior has been associated with deleterious cardiometabolic health indicators in adults, but very little research has examined this relationship in youth. PURPOSE: To examine the association between the duration and type of sedentary screen behavior with diabetes risk factors (fasting glucose, insulin, homeostasis model-insulin resistance [HOMA-IR], 2-hour postload glucose, hemoglobin A1c) in a sample of overweight and obese adolescents. METHODS: A cross-sectional study of 307 overweight or obese adolescents aged 14-18 years (90 boys, 217 girls) assessed at baseline of a lifestyle intervention for weight control conducted from 2005 to 2010. Sedentary screen behaviors, defined as hours per day spent watching TV, playing seated video games, recreational computer use, and total screen time were measured by self-report. Data were analyzed using linear regression analyses in 2012. RESULTS: TV viewing was the only type of sedentary screen behavior associated with elevated diabetes risk factors before and after adjustment for confounders. Specifically, TV viewing remained positively associated with fasting insulin (adjusted r=0.11, ß=0.10, p=0.048) and HOMA-IR (adjusted r=0.11, ß=0.10, p=0.05) after adjustment for age, gender, waist-to-hip ratio, caloric intake, percentage of intake in carbohydrates, physical activity duration, and physical activity intensity. CONCLUSIONS: TV watching may be independently associated with an increase in diabetes risk factors in a high-risk sample of overweight and obese adolescents. These findings provide support for interventions designed to reduce time spent watching TV as a possible means to attenuating diabetes risk factors in this high-risk population.

Cost-effectiveness of exercise programs in type 2 diabetes.

BACKGROUND: A randomized controlled trial has shown that supervised, facility-based exercise training is effective in improving glycemic control in type 2 diabetes. However, these programs are associated with additional costs. This analysis assessed the cost-effectiveness of such programs. METHODS: Analysis used data from the Diabetes Aerobic and Resistance Exercise (DARE) clinical trial which compared three different exercise programs (resistance, aerobic or a combination of both) of 6 months duration with a control group (no exercise program). Clinical outcomes at 6 months were entered for individual patients into the UKPDS economic model for type 2 diabetes adapted for the Canadian context. From this, expected life-years, quality-adjusted life-years (QALYs) and costs were estimated for all patients within the trial. RESULTS: The combined exercise program was the most expensive ($40,050) followed by the aerobic program ($39,250), the resistance program ($38,300) and no program ($31,075). QALYs were highest for combined (8.94), followed by aerobic (8.77), resistance (8.73) and no program (8.70). The incremental cost per QALY gained for the combined exercise program was $4,792 compared with aerobic alone, $8,570 compared with resistance alone, and $37,872 compared with no program. The combined exercise program remained cost-effective for all scenarios considered within sensitivity analysis. CONCLUSIONS: A program providing training in both resistance and aerobic exercise was the most cost-effective of the alternatives compared. Based on previous funding decisions, exercise training for individuals with diabetes can be considered an efficient use of resources.

Video game playing is independently associated with blood pressure and lipids in overweight and obese adolescents.

OBJECTIVE: To examine the association between duration and type of screen time (TV, video games, computer time) and blood pressure (BP) and lipids in overweight and obese adolescents. DESIGN: This is a cross-sectional study of 282 overweight or obese adolescents aged 14-18 years (86 males, 196 females) assessed at baseline prior to beginning a lifestyle intervention study for weight control. Sedentary behaviours, defined as hours per day spent watching TV, playing video games, recreational computer use and total screen time were measured by self-report. We examined the associations between sedentary behaviours and BP and lipids using multiple linear regression. RESULTS: Seated video gaming was the only sedentary behaviour associated with elevated BP and lipids before and after adjustment for age, sex, pubertal stage, parental education, body mass index (BMI), caloric intake, percent intake in dietary fat, physical activity (PA) duration, and PA intensity. Specifically, video gaming remained positively associated with systolic BP (adjusted r = 0.13, ß = 1.1, p<0.05) and total cholesterol/HDL ratio (adjusted r = 0.12, ß = 0.14, p<0.05). CONCLUSIONS: Playing video games was the only form of sedentary behaviour that was independently associated with increased BP and lipids. Our findings provide support for reducing time spent playing seated video games as a possible means to promote health and prevent the incidence of cardiovascular disease (CVD) risk factors in this high risk group of overweight and obese adolescents. Future research is needed to first replicate these findings and subsequently aim to elucidate the mechanisms linking seated video gaming and elevated BP and lipids in this high risk population. TRIAL REGISTRATION: Clinicaltrials.gov NCT00195858.

Effect of exercise training on physical fitness in type II diabetes mellitus.

UNLABELLED: Few studies have compared changes in cardiorespiratory fitness between aerobic training only or in combination with resistance training. In addition, no study to date has compared strength gains between resistance training and combined exercise training in type II diabetes mellitus (T2DM). PURPOSE: We evaluated the effects of aerobic exercise training (A group), resistance exercise training (R group), combined aerobic and resistance training (A + R group), and sedentary lifestyle (C group) on cardiorespiratory fitness and muscular strength in individuals with T2DM. METHODS: Two hundred and fifty-one participants in the Diabetes Aerobic and Resistance Exercise trial were randomly allocated to A, R, A + R, or C. Peak oxygen consumption (V O(2peak)), workload, and treadmill time were determined after maximal exercise testing at 0 and 6 months. Muscular strength was measured as the eight-repetition maximum on the leg press, bench press, and seated row. Responses were compared between younger (aged 39-54 yr) and older (aged 55-70 yr) adults and between sexes. RESULTS: VO(2peak) improved by 1.73 and 1.93 mL O(2)*kg(-1)*min(-1) with A and A + R, respectively, compared with C (P < 0.05). Strength improvements were significant after A + R and R on the leg press (A + R: 48%, R: 65%), bench press (A + R: 38%, R: 57%), and seated row (A + R: 33%, R: 41%; P < 0.05). There was no main effect of age or sex on training performance outcomes. There was, however, a tendency for older participants to increase VO(2peak) more with A + R (+1.5 mL O(2)*kg(-1)*min(-1)) than with A only (+0.7 mL O(2)*kg(-1)*min(-1)). CONCLUSIONS: Combined training did not provide additional benefits nor did it mitigate improvements in fitness in younger subjects compared with aerobic and resistance training alone. In older subjects, there was a trend to greater aerobic fitness gains with A + R versus A alone.