Exercise dose, exercise adherence, and associated health outcomes in the TIGER study.

PURPOSE: To effectively evaluate activity-based interventions for weight management and disease risk reduction, objective and accurate measures of exercise dose are needed. This study examined cumulative exercise exposure defined by HR-based intensity, duration, and frequency as a measure of compliance with a prescribed exercise program and a predictor of health outcomes. METHODS: One thousand one-hundred fifty adults (21.3 ± 2.7 yr) completed a 15-wk exercise protocol consisting of 30 min·d, 3 d·wk, at 65%-85% maximum HR reserve. Computerized HR monitor data were recorded at every exercise session (33,473 valid sessions). To quantify total exercise dose, duration for each session was adjusted for average exercise intensity (%HR reserve) to create a measure of intensity minutes for each workout, which were summed over all exercise sessions to formulate an HR physical activity score (HRPAS). Regression analysis was used to examine the relation between HRPAS and physiological responses to exercise training. Compliance with the exercise protocol based on achievement of the minimum prescribed HRPAS was compared with adherence defined by attendance. RESULTS: On the basis of HRPAS, 868 participants were empirically defined as compliant, and 282 were noncompliant. HRPAS-based and attendance-based classifications of compliance and adherence differed in approximately 9% of participants. Higher HRPAS was associated with significant positive changes in body mass (P < 0.001), body mass index (P < 0.001), waist and hip circumferences (P < 0.001), percent body fat (P < 0.001), systolic blood pressure (P < 0.011), resting HR (P < 0.003), fasting glucose (P < 0.001), and total cholesterol (P < 0.02). Attendance-based adherence was associated with body mass, hip circumference, percent body fat, resting HR, and cholesterol (P < 0.05). CONCLUSIONS: The HRPAS is a quantifiable measure of exercise dose associated with improvement in health indicators beyond that observed when adherence is defined as session attendance.

Acute cognitive impairment in patients with multiple myeloma undergoing autologous hematopoietic stem cell transplant.

BACKGROUND: Few studies have examined the acute effects of autologous hematopoietic stem cell transplantation (Au-HSCT) on the neuropsychological functioning of patients with multiple myeloma (MM). The prevalence of cognitive deficits after induction chemotherapy (pre-AuHSCT) was examined in patients with MM, clinically significant changes in cognitive function 1 and 3 months post-AuHSCT were determined, and patients who may be vulnerable to cognitive decline during this period were identified. METHODS: A total of 53 patients with MM were recruited pre-AuHSCT. Neuropsychological tests measuring multiple cognitive domains (attention, psychomotor speed, learning/memory, language, executive function, motor function) were administered pre-AuHSCT and 1 and 3 months post-AuHSCT. A pretreatment assessment was not available. An Overall Cognitive Function Index was computed to determine cognitive impairment pre-AuHSCT, and a practice-effect-adjusted Reliable Change Index was used to determine cognitive change over time. RESULTS: Overall, deficits were more frequent in learning/memory, executive function, motor function, and psychomotor speed. Before AuHSCT, 47% of patients (25/53) exhibited cognitive impairment as determined by the Overall Cognitive Function Index. One month post-AuHSCT, 49% of patients (20/41) demonstrated clinically significant decline on 1 or more measures; 3 months post-AuHSCT, 48% (14 of 29 patients) showed decline on 1 or more measures. Older patients, minorities, and those with advanced disease, more induction cycles, or postinduction deficits showed greater vulnerability to decline. CONCLUSIONS: Nearly half of the patients showed vulnerability to impairment in learning/memory or executive function after receiving induction therapy, and the prevalence of impairment remained high post-AuHSCT. Awareness of cognitive impairment and associated risk factors in actively treated patients is important for considering psychosocial or other support for patients with acute cognitive symptoms.

Validating the M. D. Anderson Symptom Inventory (MDASI) for use in patients with ovarian cancer.

OBJECTIVE: The M. D. Anderson Symptom Inventory (MDASI) captures the severity of common cancer symptoms from the patient's perspective. We describe the validity and sensitivity of a module of the MDASI to be used with patients having ovarian cancer (MDASI-OC). METHODS: Ovarian cancer-specific module items were developed from 14 qualitative patient interviews. 128 patients with invasive epithelial ovarian, peritoneal, or fallopian-tube cancer treated at The University of Texas MD Anderson Cancer Center were recruited. Patients completed the MDASI-OC, socio-demographic questionnaires, the Functional Assessment of Cancer Therapy-Ovary (FACT-O), and a global quality-of-life (QOL) item. Reliability was assessed using Cronbach α, and sensitivity using a known group was assessed. Construct validity was tested using exploratory factor analysis. RESULTS: The sample was primarily white (85.2%), had a mean age of 57.5 years (±12.7 years), and had previously been treated with chemotherapy (75.0%) and/or surgery (93.8%). Approximately 30% of patients reported disturbed sleep, fatigue, or numbness/tingling of at least moderate severity (≥5 on a 0-10 scale). On the ovarian-cancer-specific symptoms, approximately 20% reported back pain, feeling bloated, or constipation of at least moderate severity. Factor analysis revealed six underlying constructs (pain/sleep; cognitive; disease-related and numbness; treatment-related; affective; gastrointestinal-specific). MDASI-OC symptom and interference items had Cronbach α values of 0.90 and 0.89, respectively. The MDASI-OC was sensitive to symptom severity by performance status (p=0.009), QOL (p=0.002), and FACT-O scores (p<0.001). CONCLUSIONS: The 27-item MDASI-OC meets common criteria for validation and reliability and is sensitive to expected changes in symptoms related to differences in disease and treatment status.

Ethnic bias in anthropometric estimates of DXA abdominal fat: the TIGER study.

BACKGROUND/INTRODUCTION: The purpose of this study was to examine the race/ethnicity bias of using waist circumference (WC) to estimate abdominal fat. METHODS: A total of 771 females and 484 males (17-35 yr) were tested one to three times during a prescribed 30-wk aerobic exercise program. The race/ethnicity distribution for women was non-Hispanic white, 29%; Hispanic, 25%; African American (AA), 35%; Asian Indian, 3%; and Asian, 8%. The distribution for men was non-Hispanic white, 37%; Hispanic, 26%; AA, 22%; Asian Indian, 5%; and Asian, 10%. Abdominal fat (L1-L5) was estimated from whole-body scanning using dual-energy x-ray absorptiometry (DXA Abd-Fat). RESULTS: DXA Abd-Fat varied by race/ethnicity after accounting for WC and height in both women and men. The increase in DXA Abd-Fat per increase in WC was lower in the Asian and Asian-Indian women than that in the other women. The increase in DXA Abd-Fat per increase in WC was higher in the AA men and lower in the Asian-Indian men than that in the other men. These differential race/ethnicity effects were most notable when WC exceeded ≍90 cm in the women and ≍100 cm in the men, values which are consistent with current definitions of abdominal obesity in the United States. CONCLUSIONS: Prediction equations for abdominal fat using WC that do not account for race/ethnicity group provide biased estimates. These results may affect assessment of disease risk from abdominal obesity among racial/ethnic groups.

Exposing college students to exercise: the Training Interventions and Genetics of Exercise Response (TIGER) study.

OBJECTIVE: The Training Interventions and Genetics of Exercise Response (TIGER) study is an exercise program designed to introduce sedentary college students to regular physical activity and to identify genetic factors that influence response to exercise. PARTICIPANTS: A multiracial/ethnic cohort (N = 1,567; 39% male), age 18 to 35 years, participated in the study. METHODS: Subjects underwent 30 weeks of exercise training, 3 days/week, for 40 minutes at 65% to 85% of age- and gender-predicted maximum heart rate reserve. Multiple measures of body size/composition, heart rate, and blood pressure were obtained. RESULTS: A total of 1,567 participants, (39% male), age 18 to 35 years, participated in the TIGER study. The prevalence of overweight/obesity in participants was 48.0%/19.3% in non-Hispanic Whites, 55.3%/24.2% in Hispanic Whites, 54.9%/25.4% in African Americans, and 38.3%/11.3% in Asians. Average within-semester retention was 68%, but overall retention (30 weeks, 2 semesters) was 20%. CONCLUSIONS: The TIGER study represents an efficacious strategy for introducing college-aged individuals to regular aerobic exercise.

Generalized equations for estimating DXA percent fat of diverse young women and men: the TIGER study.

PURPOSE: Popular generalized equations for estimating percent body fat (BF%) developed with cross-sectional data are biased when applied to racially/ethnically diverse populations. We developed accurate anthropometric models to estimate dual-energy x-ray absorptiometry BF% (DXA-BF%) that can be generalized to ethnically diverse young adults in both cross-sectional and longitudinal field settings. METHODS: This longitudinal study enrolled 705 women and 428 men (aged 17-35 yr) for 30 wk of exercise training (3 d·wk(-1) for 30 min·d(-1) of 65%-85% predicted V˙O2max). The distribution of ethnicity was as follows: 37% non-Hispanic white, 29% Hispanic, and 34% African-American. DXA-BF%, skinfold thicknesses, and body mass index (BMI) were collected at baseline and after 15 and 30 wk. RESULTS: Skinfolds, BMI, and race/ethnicity were significant predictors of DXA-BF% in linear mixed model regression analysis. For comparable anthropometric measures (e.g., BMI), DXA-BF% was lower in African-American women and men but higher in Hispanic women compared with non-Hispanic white. Addition of BMI to the skinfold model improved the SEE for women (3.6% vs 4.0%), whereas BMI did not improve prediction accuracy of men (SEE = 3.1%). CONCLUSIONS: These equations provide accurate predictions of DXA-BF% for diverse young women and men in both cross-sectional and longitudinal settings. To our knowledge, these are the first published body composition equations with generalizability to multiple time points, and the SEE estimates are among the lowest published in the literature.

Direct regulation of myocardial triglyceride metabolism by the cardiomyocyte circadian clock.

Maintenance of circadian alignment between an organism and its environment is essential to ensure metabolic homeostasis. Synchrony is achieved by cell autonomous circadian clocks. Despite a growing appreciation of the integral relation between clocks and metabolism, little is known regarding the direct influence of a peripheral clock on cellular responses to fatty acids. To address this important issue, we utilized a genetic model of disrupted clock function specifically in cardiomyocytes in vivo (termed cardiomyocyte clock mutant (CCM)). CCM mice exhibited altered myocardial response to chronic high fat feeding at the levels of the transcriptome and lipidome as well as metabolic fluxes, providing evidence that the cardiomyocyte clock regulates myocardial triglyceride metabolism. Time-of-day-dependent oscillations in myocardial triglyceride levels, net triglyceride synthesis, and lipolysis were markedly attenuated in CCM hearts. Analysis of key proteins influencing triglyceride turnover suggest that the cardiomyocyte clock inactivates hormone-sensitive lipase during the active/awake phase both at transcriptional and post-translational (via AMP-activated protein kinase) levels. Consistent with increased net triglyceride synthesis during the end of the active/awake phase, high fat feeding at this time resulted in marked cardiac steatosis. These data provide evidence for direct regulation of triglyceride turnover by a peripheral clock and reveal a potential mechanistic explanation for accelerated metabolic pathologies after prevalent circadian misalignment in Western society.

Body mass index bias in defining obesity of diverse young adults: the Training Intervention and Genetics of Exercise Response (TIGER) study.

The BMI cut-score used to define overweight and obesity was derived primarily using data from Caucasian men and women. The present study evaluated the racial/ethnic bias of BMI to estimate the adiposity of young men and women (aged 17-35 years) using dual-energy X-ray absorptiometry (DXA) determination of percentage body fat (DXA-BF%) as the referent standard. The samples were 806 women and 509 men who were tested from one to three times over 9 months providing 1300 observations for women and 820 observations for men. Linear mixed models (LMM) regression showed that with age and BMI controlled, DXA-BF% of African-American (AA) men and women, Asian-Indian men and women, Hispanic women and Asian women significantly differed from non-Hispanic white (NHW) men and women. For the same BMI of NHW women, the DXA-BF% of AA women was 1.76 % lower, but higher for Hispanic (1.65 %), Asian (2.65 %) and Asian-Indian (5.98 %) women. For the same BMI of NHW men, DXA-BF% of AA men was 4.59 % lower and 4.29 % higher for Asian-Indian men. Using the recommended BMI cut-scores to define overweight and obesity systematically overestimated overweight and obesity prevalence for AA men and women, and underestimated prevalence for Asian-Indian men and women, Asian women and Hispanic women. The present study extends the generalisability of research documenting the racial/ethnic bias of the universal overweight and obesity BMI cut-scores.

Cross-validation of generalised body composition equations with diverse young men and women: the Training Intervention and Genetics of Exercise Response (TIGER) Study.

Generalised skinfold equations developed in the 1970s are commonly used to estimate laboratory-measured percentage fat (BF%). The equations were developed on predominately white individuals using Siri's two-component percentage fat equation (BF%-GEN). We cross-validated the Jackson-Pollock (JP) generalised equations with samples of young white, Hispanic and African-American men and women using dual-energy X-ray absorptiometry (DXA) as the BF% referent criterion (BF%-DXA). The cross-sectional sample included 1129 women and men (aged 17-35 years). The correlations between BF%-GEN and BF%-DXA were 0.85 for women and 0.93 for men. Analysis of measurement error showed that BF%-GEN underestimated BF%-DXA of men and women by 1.3 and 3.0 %. General linear models (GLM) confirmed that BF%-GEN systematically underestimated BF%-DXA of Hispanic men and women, and overestimated BF%-DXA of African-American men. GLM were used to estimate BF%-DXA from the JP sum of skinfolds and to account for race/ethnic group bias. The fit statistics (R and standard error of the estimate; see) of the men's calibration model were: white, R 0.92, see 3.0 %; Hispanic, R 0.91, see 3.0 %; African-American, R 0.95, see 2.6 %. The women's statistics were: white and African-American, R 0.86, see 3.8 %; Hispanic, R 0.83, see 3.4 %. These results showed that BF%-GEN and BF%-DXA were highly correlated, but the error analyses documented that the generalised equations lacked accuracy when applied to these racially and ethnically diverse men and women. The inaccuracy was linked to the body composition and race/ethnic differences between these Training Intervention and Genetics of Exercise Response (TIGER) study subjects and the men and women used to develop the generalised equations in the 1970s and using BF%-DXA as the referent criterion.