Susan B. Roberts

Exercise Training and Nutritional Supplementation for Physical Frailty in Very Elderly People

BACKGROUND Although disuse of skeletal muscle and undernutrition are often cited as potentially reversible causes of frailty in elderly people, the efficacy of interventions targeted specifically at these deficits has not been carefully studied. METHODS We conducted a randomized, placebo-controlled trial comparing progressive resistance exercise training, multinutrient supplementation, both interventions, and neither in 100 frail nursing home residents over a 10-week period. RESULTS The mean (+/- SE) age of the 63 women and 37 men enrolled in the study was 87.1 +/- 0.6 years (range, 72 to 98); 94 percent of the subjects completed the study. Muscle strength increased by 113 +/- 8 percent in the subjects who underwent exercise training, as compared with 3 +/- 9 percent in the nonexercising subjects (P < 0.001). Gait velocity increased by 11.8 +/- 3.8 percent in the exercisers but declined by 1.0 +/- 3.8 percent in the nonexercisers (P = 0.02). Stair-climbing power also improved in the exercisers as compared with the nonexercisers (by 28.4 +/- 6.6 percent vs. 3.6 +/- 6.7 percent, P = 0.01), as did the level of spontaneous physical activity. Cross-sectional thigh-muscle area increased by 2.7 +/- 1.8 percent in the exercisers but declined by 1.8 +/- 2.0 percent in the nonexercisers (P = 0.11). The nutritional supplement had no effect on any primary outcome measure. Total energy intake was significantly increased only in the exercising subjects who also received nutritional supplementation. CONCLUSIONS High-intensity resistance exercise training is a feasible and effective means of counteracting muscle weakness and physical frailty in very elderly people. In contrast, multi-nutrient supplementation without concomitant exercise does not reduce muscle weakness or physical frailty.

Nonsurgical factors that influence the outcome of bariatric surgery: a review.

Objective Severe obesity (ie, at least 100% overweight or body mass index >or=to40 kg/m2) is associated with significant morbidity and increased mortality. It is apparently becoming more common in this country. Conventional weight-loss treatments are usually ineffective for severe obesity and bariatric surgery is recommended as a treatment option. However, longitudinal data on the long-term outcome of bariatric surgery are sparse. Available data indicate that the outcome of bariatric surgery, although usually favorable in the short term, is variable and weight regain sometimes occurs at 2 years after surgery. The objective of this study is to present a review of the outcome of bariatric surgery in three areas: weight loss and improvement in health status, changes in eating behavior, and psychosocial adjustment. The study will also review how eating behavior, energy metabolism, and psychosocial functioning may affect the outcome of bariatric surgery. Suggestions for additional research in these areas are made. Method Literature review. Results On average, most patients lose 60% of excess weight after gastric bypass and 40% after vertical banded gastroplasty. In about 30% of patients, weight regain occurs at 18 months to 2 years after surgery. Binge eating behavior, which is common among the morbidly obese, may recur after surgery and is associated with weight regain. Energy metabolism may affect the outcome of bariatric surgery, but it has not been systematically studied in this population. Presurgery psychosocial functioning does not seem to affect the outcome of surgery, and psychosocial outcome is generally encouraging over the short term, but there are reports of poor adjustment after weight loss, including alcohol abuse and suicide. Conclusions Factors leading to poor outcome of bariatric surgery, such as binge eating and lowered energy metabolism, should be studied to improve patient selection and outcome. Long-term outcome data on psychosocial functioning are lacking. Longitudinal studies to examine the long-term outcome of bariatric surgery and the prognostic indicators are needed.

Energy Expenditure and Intake in Infants Born to Lean and Overweight Mothers

We investigated the contributions of low energy expenditure and high energy intake to excessive weight gain in infants born to overweight mothers. The subjects were infants of 6 lean and 12 overweight mothers, recruited soon after birth. Total energy expenditure and metabolizable energy intake were measured with a new doubly labeled water method over a period of seven days when the infants were 3 months of age, and the postprandial metabolic rate was measured by indirect calorimetry when the infants were 0.1 and 3 months of age. The results were related to weight gain in the first year of life. No significant difference was observed between infants who became overweight by the age of one year (50 percent of infants born to overweight mothers) and those who did not, with respect to weight, length, skinfold thicknesses, metabolic rate at 0.1 and 3 months of age, and metabolizable energy intake at 3 months. However, total energy expenditure at three months of age was 20.7 percent lower in the infants who became overweight than in the other infants (means +/- SE, 256 +/- 27 and 323 +/- 12 kJ per kilogram of body weight per day; P less than 0.05). This difference could account for the mean difference in weight gain. These data suggest that reduced energy expenditure, particularly on physical activity, was an important factor in the rapid weight gain during the first year of life in infants born to overweight mothers.

Binge eating disorder in extreme obesity.

OBJECTIVE: To determine whether extremely obese binge eating disorder (BED) subjects (BED defined by the Eating Disorder Examination) differ from their extremely obese non-BED counterparts in terms of their eating disturbances, psychiatric morbidity and health status.DESIGN: Prospective clinical comparison of BED and non-BED subjects undergoing gastric bypass surgery (GBP).SUBJECTS: Thirty seven extremely obese (defined as BMI ≥40 kg/m2) subjects (31 women, six men), aged 22–58 y.MEASUREMENTS: Eating Disorder Examination 12th Edition (EDE), Three Factor Eating Questionnaire (TFEQ), Structured Clinical Interview for the Diagnostic and Statistical Manual-IV (SCID-IV), Short-Form Health Status Survey (SF-36), and 24 h Feeding Paradigm.RESULTS: Twenty-five percent of subjects were classified as BED (11% met full and 14% partial BED criteria) and 75% of subjects were classified as non-BED. BED (full and partial) subjects had higher eating disturbance in terms of eating concern and shape concern (as found by the EDE), higher disinhibition (as found by the TFEQ), and they consumed more liquid meal during the 24 h feeding paradigm. No difference was found in psychiatric morbidity between BED and non-BED in terms of DSM-IV Axis I diagnosis. The health status scores of both BED and non-BED subjects were significantly lower than US norms on all subscales of the SF-36, particularly the BED group.CONCLUSION: Our findings support the validity of the category of BED within a population of extremely obese individuals before undergoing GBP. BED subjects differed from their non-BED counterparts in that they had a greater disturbance in eating attitudes and behavior, a poorer physical and mental health status, and a suggestion of impaired hunger/satiety control. However, in this population of extremely obese subjects, the stability of BED warrants further study.

Genotypic and phenotypic analysis of variants resistant to hepatitis C virus nonstructural protein 5A replication complex inhibitor BMS‐790052 in Humans: In Vitro and In Vivo Correlations

The NS5A replication complex inhibitor, BMS‐790052, inhibits hepatitis C virus (HCV) replication with picomolar potency in preclinical assays. This potency translated in vivo to a substantial antiviral effect in a single‐ascending dose study and a 14‐day multiple‐ascending dose (MAD) monotherapy study. However, HCV RNA remained detectable in genotype 1a–infected patients at the end of the MAD study. In contrast, viral breakthrough was observed less often in patients infected with genotype 1b, and, in several patients, HCV RNA declined and remained below the level of quantitation (<25 IU/mL) through the duration of treatment. Here, we report on the results of the genotypic and phenotypic analyses of resistant variants in 24 genotype 1–infected patients who received BMS‐790052 (1, 10, 30, 60, and 100 mg, once‐daily or 30 mg twice‐daily) in the 14‐day MAD study. Sequence analysis was performed on viral complementary DNA isolated from serum specimens collected at baseline and days 1 (4, 8, and 12 hours), 2, 4, 7, and 14 postdosing. Analyses of the sequence variants (1) established a correlation between resistant variants emerging in vivo with BMS‐790052 treatment and those observed in the in vitro replicon system (major substitutions at residues 28, 30, 31, and 93 for genotype 1a and residues 31 and 93 for genotype 1b); (2) determined the prevalence of variants at baseline and the emergence of resistance at different times during dosing; and (3) revealed the resistance profile and replicative ability (i.e., fitness) of the variants. Conclusion: Although resistance emerged during monotherapy with BMS‐790052, the substantial anti‐HCV effect of this compound makes it an excellent candidate for effective combination therapy. (HEPATOLOGY 2011)

Eating patterns and dietary composition in relation to BMI in younger and older adults

Objective:To compare relative associations of eating patterns and dietary composition with body mass index (BMI) in younger (aged 20–59 years, n=1792) and older (aged 60–90 years, n=893) participants in the Continuing Survey of Food Intakes by Individuals, collected 1994–1996.Methods:Data from two 24-h dietary recalls from individuals reporting physiologically plausible energy intake (within ±22% of predicted energy requirements, based on previously published methods) were used.Results:Mean reported energy intake was 96 and 95% of predicted energy requirements in younger and older subjects, respectively. Older subjects were less likely than younger subjects to skip a meal, but snacking was common in both age groups. Fiber density was significantly higher in the older group. A higher BMI in both age groups was associated with a higher total daily energy intake, and higher energy intakes at all eating occasions. In both age groups, eating frequency was positively associated with energy intake, and eating more than three times a day was associated with being overweight or obese. In the younger group but not the older group, a lower fiber density coupled with higher percentage of energy from fat was independently associated with having a higher BMI.Conclusions:While no one eating occasion contributes more than any other to excess adiposity, eating more often than three times a day may play a role in overweight and obesity in both younger and older persons. A reduced satiety response to dietary fiber in addition to lower energy expenditure may potentially further contribute to weight gain in older persons.

Dynamics of β-Amyloid Reductions in Brain, Cerebrospinal Fluid, and Plasma of β-Amyloid Precursor Protein Transgenic Mice Treated with a γ-Secretase Inhibitor

γ-Secretase inhibitors are one promising approach to the development of a therapeutic for Alzheimers disease (AD). γ-Secretase inhibitors reduce brain β-amyloid peptide (Aβ), which is believed to be a major contributor in the etiology of AD. Transgenic mice overexpressing the human β-amyloid precursor protein (APP) are valuable models to examine the dynamics of Aβ changes with γ-secretase inhibitors in plaque-free and plaque-bearing animals. BMS-299897 2-[(1R)-1-[[(4-chlorophenyl)sulfony](2,5-difluorophenyl)amino]ethyl]-5-fluorobenzenepropanoic acid, a γ-secretase inhibitor, showed dose- and time dependent reductions of Aβ in brain, cerebrospinal fluid (CSF), and plasma in young transgenic mice, with a significant correlation between brain and CSF Aβ levels. Because CSF and brain interstitial fluid are distinct compartments in composition and location, this correlation could not be assumed. In contrast, aged transgenic mice with large accumulations of Aβ in plaques showed reductions in CSF Aβ in the absence of measurable changes in plaque Aβ in the brain after up to 2 weeks of treatment. Hence, CSF Aβ levels were a valuable measure of γ-secretase activity in the central nervous system in either the presence or absence of plaques. Transgenic mice were also used to examine potential side effects due to Notch inhibition. BMS-299897 was 15-fold more effective at preventing the cleavage of APP than of Notch in vitro. No changes in the maturation of CD8+ thymocytes or of intestinal goblet cells were observed in mice treated with BMS-299897, showing that it is possible for γ-secretase inhibitors to reduce brain Aβ without causing Notch-mediated toxicity.

Aspects of eating behaviors "disinhibition" and "restraint" are related to weight gain and BMI in women.

Objective: The causes of adult weight gain leading to obesity are uncertain. We examined the association of adult weight gain and obesity with subscales of eating behavior characteristics in older women.

Cardiac rehabilitation programmes: predictors of non-attendance and drop-out:

Background Despite evidence of its benefits, attendance at cardiac rehabilitation (CR) programmes is poor. Past studies to identify predictors of non-attendance have been limited by their small sample size, particularly for female patients. The present study was designed to identify socio-demographic and clinical predictors of non-attendance and drop-out separately for men and women automatically referred to CR programmes. Method and subjects Prospective study of CR programme attendance amongst 808 patients consecutively admitted over an 11-month period to one of two hospitals in Melbourne, Australia, after acute myocardial infarction (AMI), or to undergo coronary artery bypass graft surgery (CABGS) or percutaneous coronary intervention (PCI). Results Of the 652 eligible patients, 573 (88%) were successfully tracked at 4 months. Of these, 284 (49.6%) had attended a CR programme, while 272 (47.5%) had not. Using logistic regression, the significant predictors of programme non-attendance among men were having had a PCI, being a non-driver, and being aged 70 or more. The only factor predictive of non-attendance for women was being aged 70 or more. Amongst attenders, 67 (23.6%) patients discontinued the programme. Being a smoker, having diabetes and being unemployed at the time of hospital admission were predictive of programme drop-out by men. Being physically inactive at admission was predictive of programme drop-out by women. Conclusions The present study demonstrated a relatively high rate of CR programme attendance. Special attention needs to be directed towards males who are older, PCI patients, smokers, unemployed or non-drivers, and females who are older or inactive.

Procedures for screening out inaccurate reports of dietary energy intake

OBJECTIVE To review existing methods and illustrate the use of a new, simple method for identifying inaccurate reports of dietary energy intake (rEI). DESIGN Comparison of rEI with energy requirements estimated by using total energy expenditure predicted (pTEE) from age, weight, height and sex using a previously published equation. Propagation of error calculations was performed and cut-offs for excluding rEI at plus or minus two standard deviations (+/-2 SD) and +/-1 SD for the agreement between rEI and pTEE were established. SETTING Dietary survey in a US national cohort: the Continuing Survey of Food Intakes by Individuals (CSFII), 1994-96. SUBJECTS Men and non-pregnant, non-lactating women aged 21-45 years in the CSFII who provided two multiple-pass 24-hour recalls, height and weight (n = 3755). RESULTS Average rEI was 77% of pTEE in men, and 64% of pTEE in women. Calculated cut-offs were rEI <40% or >160% of pTEE (+/-2 SD) and <70% or >130% of pTEE (+/-1 SD), respectively. Use of only the +/-1 SD cut-offs, not the +/-2 SD cut-offs, resulted in a relationship between rEI and body weight similar to what was expected (based on an independently calculated relationship between rEI and measured TEE). Exclusion of rEI outside either the +/-2 SD (11% of subjects) or +/-1 SD (57% of subjects) cut-offs did not affect mean reported macronutrient intakes, but did markedly affect relationships between dietary composition and body mass index. CONCLUSIONS When examining relationships between diet and health, use of +/-1 SD cut-offs may be preferable to +/-2 SD cut-offs for excluding inaccurate dietary reports.