Amy M. Schrader

Quantity of dietary protein intake, but not pattern of intake, affects net protein balance primarily through differences in protein synthesis in older adults

To examine whole body protein turnover and muscle protein fractional synthesis rate (MPS) following ingestions of protein in mixed meals at two doses of protein and two intake patterns, 20 healthy older adult subjects (52-75 yr) participated in one of four groups in a randomized clinical trial: a level of protein intake of 0.8 g (1RDA) or 1.5 g·kg(-1)·day(-1) (∼2RDA) with uneven (U: 15/20/65%) or even distribution (E: 33/33/33%) patterns of intake for breakfast, lunch, and dinner over the day (1RDA-U, 1RDA-E, 2RDA-U, or 2RDA-E). Subjects were studied with primed continuous infusions of L-[(2)H5]phenylalanine and L-[(2)H2]tyrosine on day 4 following 3 days of diet habituation. Whole body protein kinetics [protein synthesis (PS), breakdown, and net balance (NB)] were expressed as changes from the fasted to the fed states. Positive NB was achieved at both protein levels, but NB was greater in 2RDA vs. 1RDA (94.8 ± 6.0 vs. 58.9 ± 4.9 g protein/750 min; P = 0.0001), without effects of distribution on NB. The greater NB was due to the higher PS with 2RDA vs. 1RDA (15.4 ± 4.8 vs. -18.0 ± 8.4 g protein/750 min; P = 0.0018). Consistent with PS, MPS was greater with 2RDA vs. 1RDA, regardless of distribution patterns. In conclusion, whole body net protein balance was greater with protein intake above recommended dietary allowance (0.8 g protein·kg(-1)·day(-1)) in the context of mixed meals, without demonstrated effects of protein intake pattern, primarily through higher rates of protein synthesis at whole body and muscle levels.

The anabolic response to a meal containing different amounts of protein is not limited by the maximal stimulation of protein synthesis in healthy young adults

We have determined whole body protein kinetics, i.e., protein synthesis (PS), breakdown (PB), and net balance (NB) in human subjects in the fasted state and following ingestion of ~40 g [moderate protein (MP)], which has been reported to maximize the protein synthetic response or ~70 g [higher protein (HP)] protein, more representative of the amount of protein in the dinner of an average American diet. Twenty-three healthy young adults who had performed prior resistance exercise (X-MP or X-HP) or time-matched resting (R-MP or R-HP) were studied during a primed continuous infusion of l-[(2)H5]phenylalanine and l-[(2)H2]tyrosine. Subjects were randomly assigned into an exercise (X, n = 12) or resting (R, n = 11) group, and each group was studied at the two levels of dietary protein intake in random order. PS, PB, and NB were expressed as increases above the basal, fasting values (mg·kg lean body mass(-1)·min(-1)). Exercise did not significantly affect protein kinetics and blood chemistry. Feeding resulted in positive NB at both levels of protein intake: NB was greater in response to the meal containing HP vs. MP (P < 0.00001). The greater NB with HP was achieved primarily through a greater reduction in PB and to a lesser extent stimulation of protein synthesis (for all, P < 0.0001). HP resulted in greater plasma essential amino acid responses (P < 0.01) vs. MP, with no differences in insulin and glucose responses. In conclusion, whole body net protein balance improves with greater protein intake above that previously suggested to maximally stimulating muscle protein synthesis because of a simultaneous reduction in protein breakdown.

Association Between Quality Measures and Mortality in Individuals With Co-Occurring Mental Health and Substance Use Disorders ☆

IMPORTANCE Individuals with co-occurring mental and substance use disorders have increased rates of mortality relative to the general population. The relationship between measures of treatment quality and mortality for these individuals is unknown. OBJECTIVE To examine the association between 5 quality measures and 12- and 24-month mortality. DESIGN, SETTING AND PARTICIPANTS Retrospective cohort study of patients with co-occurring mental illness (schizophrenia, bipolar disorder, post-traumatic stress disorder and major depression) and substance use disorders who received care for these disorders paid for by the Veterans Administration between October 2006 and September 2007. Logistic regression models were used to examine the association between 12 and 24-month mortality and 5 patient-level quality measures, while risk-adjusting for patient characteristics. Quality measures included receipt of psychosocial treatment, receipt of psychotherapy, treatment initiation and engagement, and a measure of continuity of care. We also examined the relationship between number of diagnosis-related outpatient visits and mortality, and conducted sensitivity analyses to examine the robustness of our findings to an unobserved confounder. MAIN OUTCOMES MEASURE Mortality 12 and 24 months after the end of the observation period. RESULTS All measures except for treatment engagement at 24 months were significantly associated with lower mortality at both 12 and 24 months. At 12 months, receiving any psychosocial treatment was associated with a 21% decrease in mortality; psychotherapy, a 22% decrease; treatment initiation, a 15% decrease, treatment engagement, a 31% decrease; and quarterly, diagnosis-related visits a 28% decrease. Increasing numbers of visits were associated with decreasing mortality. Sensitivity analyses indicated that the difference in the prevalence of an unobserved confounder would have to be unrealistically large given the observed data, or there would need to be a large effect of an unobserved confounder, to render these findings non-significant. CONCLUSIONS AND RELEVANCE This is the first study to show an association between process-based quality measures and mortality in patients with co-occurring mental and substance use disorders, and provides initial support for the predictive validity of the measures. By devising strategies to improve performance on these measures, health care systems may be able to decrease the mortality of this vulnerable population.

Acute ingestion of citrulline stimulates nitric oxide synthesis but does not increase blood flow in healthy young and older adults with heart failure

To determine if age-associated vascular dysfunction in older adults with heart failure (HF) is due to insufficient synthesis of nitric oxide (NO), we performed two separate studies: 1) a kinetic study with a stable isotope tracer method to determine in vivo kinetics of NO metabolism, and 2) a vascular function study using a plethysmography method to determine reactive hyperemic forearm blood flow (RH-FBF) in older and young adults in the fasted state and in response to citrulline ingestion. In the fasted state, NO synthesis (per kg body wt) was ∼ 50% lower in older vs. young adults and was related to a decreased rate of appearance of the NO precursor arginine. Citrulline ingestion (3 g) stimulated de novo arginine synthesis in both older [6.88 ± 0.83 to 35.40 ± 4.90 μmol · kg body wt(-1) · h(-1)] and to a greater extent in young adults (12.02 ± 1.01 to 66.26 ± 4.79 μmol · kg body wt(-1) · h(-1)). NO synthesis rate increased correspondingly in older (0.17 ± 0.01 to 2.12 ± 0.36 μmol · kg body wt(-1) · h(-1)) and to a greater extent in young adults (0.36 ± 0.04 to 3.57 ± 0.47 μmol · kg body wt(-1) · h(-1)). Consistent with the kinetic data, RH-FBF in the fasted state was ∼ 40% reduced in older vs. young adults. However, citrulline ingestion (10 g) failed to increase RH-FBF in either older or young adults. In conclusion, citrulline ingestion improved impaired NO synthesis in older HF adults but not RH-FBF, suggesting that factors other than NO synthesis play a role in the impaired RH-FBF in older HF adults, and/or it may require a longer duration of supplementation to be effective in improving RH-FBF.

Association Between Process Measures and Mortality in Individuals with Opioid Use Disorders

BACKGROUND Individuals with opioid use disorders have high rates of mortality relative to the general population. The relationship between treatment process and mortality is unknown. AIM To examine the association between 7 process measures and 12- and 24-month mortality. METHODS Retrospective cohort study of patients with opioid use disorders who received care from the Veterans Administration between October 2006 and September 2007. Logistic regression models were used to examine the association between 12 and 24-month mortality and 7 patient-level process measures, while risk-adjusting for patient characteristics. Process measures included quarterly physician visits, any opioid use disorder pharmacotherapy, continuous pharmacotherapy, psychosocial treatment, Hepatitis B/C and HIV screening, and no prescriptions for benzodiazepines or opioids. We conducted sensitivity analyses to examine the robustness of our findings to an unobserved confounder. RESULTS Among individuals with opioid use disorders, not being prescribed opioids or benzodiazepines, receipt of any psychosocial treatment and quarterly physician visits were significantly associated with lower mortality at both 12 and 24 months, but Hepatitis and HIV screening, and measures related to opioid use disorder pharmacotherapy were not. Sensitivity analyses indicated that the difference in the prevalence of an unobserved confounder would have to be unrealistically large given the observed data, or there would need to be a large effect of the confounder, to render these findings non-significant. CONCLUSIONS AND RELEVANCE This is the first study to show an association between process measures and mortality in patients with opioid use disorders and provides initial evidence for their use as quality measures.

Association Between Quality Measures and Perceptions of Care Among Patients With Substance Use Disorders

OBJECTIVE This study evaluated whether eight quality measures assessing care for patients with a substance use disorder were associated with patient perceptions of their care, including perceived improvement and global rating of behavioral health care. METHODS Secondary data analyses were conducted of administrative and patient survey data collected as part of a national evaluation of Veterans Health Administration (VHA) mental health and substance use services. Data for patients who received care for substance use disorders during October 2006-September 2007 paid for by the VHA and who participated in a telephone interview about their care (N=2,074) were included. Measures of patient perceptions of care included perceived improvement and global rating of behavioral health care. Eight quality measures based on administrative data assessed initiation and engagement in substance use disorder care, receipt of psychotherapy or psychosocial treatment, and follow-up after hospitalization. Regression models were conducted in which each quality measure predicted each outcome, with analyses adjusting for patient characteristics and functioning. RESULTS Treatment engagement, two measures of psychotherapy receipt, and psychosocial treatment were significantly associated with perceived improvement, whereas treatment initiation and follow-up after hospitalization (seven and 30 days) were not. Psychotherapy receipt and follow-up after hospitalization (seven and 30 days) were significantly associated with global rating of behavioral health care. CONCLUSIONS Some quality measures assessing care for substance use disorders were significantly associated with patient perceptions of care. Results provide additional support for these quality measures and suggest that patient perceptions of care are an important outcome in assessing care.

Hydration health literacy in the elderly

BACKGROUND: Inadequate hydration in the elderly is associated with increased morbidity and mortality. However, few studies have addressed the knowledge of elderly individuals regarding hydration in health and disease. Gaps in health literacy have been identified as a critical component in health maintenance, and promoting health literacy should improve outcomes related to hydration associated illnesses in the elderly. METHODS: We administered an anonymous survey to community-dwelling elderly (n = 170) to gauge their hydration knowledge. RESULTS: About 56% of respondents reported consuming >6 glasses of fluid/day, whereas 9% reported drinking ≤3 glasses. About 60% of respondents overestimated the amount of fluid loss at which moderately severe dehydration symptoms occur, and 60% did not know fever can cause dehydration. Roughly 1/3 were not aware that fluid overload occurs in heart failure (35%) or kidney failure (32%). A majority of respondents were not aware that improper hydration or changes in hydration status can result in confusion, seizures, or death. CONCLUSIONS: Overall, our study demonstrated that there were significant deficiencies in hydration health literacy among elderly. Appropriate education and attention to hydration may improve quality of life, reduce hospitalizations and the economic burden related to hydration-associated morbidity and mortality.

Feasibility of Conducting a 6-Months Long Home-based Exercise Program withProtein Supplementation in Elderly Community-dwelling Individuals with Heart Failure

Objective Cardiac cachexia is a condition associated with heart failure, particularly in the elderly, and is characterized by loss of muscle mass with or without the loss of fat mass. Approximately 15% of elderly heart failure patients will eventually develop cardiac cachexia; such a diagnosis is closely associated with high morbidity and increased mortality. While the mechanism(s) involved in the progression of cardiac cachexia is incompletely established, certain factors appear to be contributory. Dietary deficiencies, impaired bowel perfusion, and metabolic dysfunction all contribute to reduced muscle mass, increased muscle wasting, increased protein degradation, and reduced protein synthesis. Thus slowing or preventing the progression of cardiac cachexia relies heavily on dietary and exercise-based interventions in addition to standard heart failure treatments and medications. Methods The aim of the present study was to test the feasibility of an at-home exercise and nutrition intervention program in a population of elderly with heart failure, in an effort to determine whether dietary protein supplementation and increased physical activity may slow the progression, or prevent the onset, of cardiac cachexia. Frail elderly patients over the age of 55 with symptoms of heart failure from UAMS were enrolled in one of two groups, intervention or control. To assess the effect of protein supplementation and exercise on the development of cardiac cachexia, data on various measures of muscle quality, cardiovascular health, mental status, and quality of life were collected and analyzed from the two groups at the beginning and end of the study period. Results More than 50% of those who were initially enrolled actually completed the 6-month study. While both groups showed some improvement in their study measures, the protein and exercise group showed a greater tendency to improve than the control group by the end of the six months. Conclusion These findings suggest that with a larger cohort, this intervention may show significant positive effects for elderly patients who are at risk of developing cardiac cachexia.

Abstract 267: Demographic differences in patients diagnosed with breast neoplasms living in Arkansas counties that have a history of a high percentage of crop land

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Cancer is the second leading cause of death in Arkansas, and obesity is a significant co-morbidity. Understanding how obesity interacts with environmental exposures to influence cancer rates is critical to the health of Arkansans. Agriculture is the largest industry in Arkansas, and positive associations between BMI, pesticide exposure and breast cancer incidence in pesticide applicators have been reported, possibly due to perturbations in hormones and oxidative stress. The primary goal of the current study is to explore the roles of BMI and county of residence in women with breast neoplasm diagnoses utilizing the UAMS Data Warehouse dataset (a collection of data on patients treated at a University of Arkansas for Medical Sciences facility [1999-2012]). This case-case study identified Arkansas counties with either a high or low percentage of cropland in 1987. Eighteen counties were pair-matched within each group based on population and cancer cases, with 272 and 271 patients residing in high and low percentage of cropland respectively who had malignant breast neoplasm diagnoses. Adjusted odds ratios were calculated using logistic regression. With percentage of cropland (high vs. low) as the response variable and independent variables of race, age and BMI, Caucasians [OR 3.461; CI (1.954, 6.129)] were significantly higher within the low cropland than the high cropland, and age at diagnosis [OR 0.979; (0.963, 0.995)] was significantly lower within the high cropland than the low cropland. When the model was stratified by race (Caucasian and non-Caucasians), age at diagnosis [OR 0.977; CI (0.959, 0.995)] was significantly lower within the high cropland than the low cropland for Caucasians. No significant differences were found among non-Caucasians between high and low of cropland. When the model was stratified by BMI (normal/underweight and overweight/obese), Caucasians [OR 4.222; CI (2.114, 8.436)] were significantly higher within low cropland than the high cropland for overweight/obese patients and age at diagnosis [OR 0.972; CI (0.947, 0.998)] was significantly lower within the high cropland than the low cropland for normal/underweight patients. Within the high cropland population, using race as a response variable, BMI (OR 0.427; CI 0.28, 0.66) was significantly higher and age at diagnosis (OR 1.17; CI 1.04, 1.32) was significantly lower for non-Caucasians. These data demonstrate a difference in breast cancer patients both between high and low cropland counties, and within the high cropland counties in Arkansas. Thus, BMI and environmental exposures could interact to influence breast cancer risk in agricultural communities. With the growing obesity epidemic, understanding how these factors are related are critical in the design of cancer prevention strategies. Citation Format: Rosalind B. Penney, Bryant Phelan, Amy M. Schrader, Page Moore, Susan A. Kadlubar. Demographic differences in patients diagnosed with breast neoplasms living in Arkansas counties that have a history of a high percentage of crop land. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 267. doi:10.1158/1538-7445.AM2014-267