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- All Subjects: Chemotherapy
- All Subjects: Physical Activity
- Creators: Dickinson, Jared
Description
Background: Heart failure is the leading cause of hospitalization in older adults and has the highest 30-day readmission rate of all diagnoses. An estimated 30 to 60 percent of older adults lose some degree of physical function in the course of an acute hospital stay. Few studies have addressed the role of posture and mobility in contributing to, or improving, physical function in older hospitalized adults. No study to date that we are aware of has addressed this in the older heart failure population.
Purpose: To investigate the predictive value of mobility during a hospital stay and patterns of mobility during the month following discharge on hospital readmission and 30-day changes in functional status in older heart failure patients.
Methods: This was a prospective observational study of 21 older (ages 60+) patients admitted with a primary diagnosis of heart failure. Patients wore two inclinometric accelerometers (rib area and thigh) to record posture and an accelerometer placed at the ankle to record ambulatory activity. Patients wore all sensors continuously during hospitalization and the ankle accelerometer for 30 days after hospital discharge. Function was assessed in all patients the day after hospital discharge and again at 30 days post-discharge.
Results: Five patients (23.8%) were readmitted within the 30 day post-discharge period. None of the hospital or post-discharge mobility measures were associated with readmission after adjustment for covariates. Higher percent lying time in the hospital was associated with slower Timed Up and Go (TUG) time (b = .08, p = .01) and poorer hand grip strength (b = -13.94, p = .02) at 30 days post-discharge. Higher daily stepping activity during the 30 day post-discharge period was marginally associated with improvements in SPPB scores at 30 days (b = <.001, p = .06).
Conclusion: For older heart failure patients, increased time lying while hospitalized is associated with slower walking time and poor hand grip strength 30 days after discharge. Higher daily stepping after discharge may be associated with improvements in physical function at 30 days.
Purpose: To investigate the predictive value of mobility during a hospital stay and patterns of mobility during the month following discharge on hospital readmission and 30-day changes in functional status in older heart failure patients.
Methods: This was a prospective observational study of 21 older (ages 60+) patients admitted with a primary diagnosis of heart failure. Patients wore two inclinometric accelerometers (rib area and thigh) to record posture and an accelerometer placed at the ankle to record ambulatory activity. Patients wore all sensors continuously during hospitalization and the ankle accelerometer for 30 days after hospital discharge. Function was assessed in all patients the day after hospital discharge and again at 30 days post-discharge.
Results: Five patients (23.8%) were readmitted within the 30 day post-discharge period. None of the hospital or post-discharge mobility measures were associated with readmission after adjustment for covariates. Higher percent lying time in the hospital was associated with slower Timed Up and Go (TUG) time (b = .08, p = .01) and poorer hand grip strength (b = -13.94, p = .02) at 30 days post-discharge. Higher daily stepping activity during the 30 day post-discharge period was marginally associated with improvements in SPPB scores at 30 days (b = <.001, p = .06).
Conclusion: For older heart failure patients, increased time lying while hospitalized is associated with slower walking time and poor hand grip strength 30 days after discharge. Higher daily stepping after discharge may be associated with improvements in physical function at 30 days.
ContributorsFloegel, Theresa A (Author) / Buman, Matthew P (Thesis advisor) / Hooker, Steven (Committee member) / Dickinson, Jared (Committee member) / DerAnanian, Cheryl (Committee member) / McCarthy, Marianne (Committee member) / Arizona State University (Publisher)
Created2015
Description
The purpose of this project is to explore the benefit of using prodrugs in chemotherapy, as well as to explain the concept of angiogenesis and the importance of this process to tumor development. Angiogenesis is the formation of new blood capillaries that are necessary for the survival of a tumor, as a tumor cannot grow larger than 1-2 mm3 without developing its own blood supply. Vascular disrupting agents, such as iodocombstatin, a derivative of combretastatin, can be used to effectively cut off the blood supply to a growing neoplasm, effectively inhibiting the supply of oxygen and nutrients needed for cell division Thus, VDAs have a very important implication in terms of the future of chemotherapy. A prodrug, defined as an agent that is inactive in the body until metabolized to yield the drug itself, was synthesized by combining iodocombstatin with a β-glucuronide linker. The prodrug is theoretically hydrolyzed in the body to afford the active drug by β-glucuronidase, an enzyme that is produced five times as much by cancer cells as by normal cells. This effectively creates a “magic-bullet” form of chemotherapy, known as Direct Enzyme Prodrug Therapy (DEPT).
ContributorsClark, Caroline Marie (Author) / Pettit, George Robert (Thesis director) / Melody, Noeleen (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2015-05
Description
The anthracycline drug Doxorubicin (DOX) is a highly effective treatment for breast cancer, but its clinical utility is limited by dose-dependent cardiovascular toxicity. The toxic effects are partly attributed to DOX-induced generation of reactive oxygen species, which may impair nitric oxide-mediated vasodilation. Exercise training activates antioxidant defense mechanisms and is thus hypothesized to counteract oxidative stress when initiated prior to DOX administration. Adult 8-week old, ovariectomized female Sprague-Dawley rats were divided into 4 groups: sedentary + vehicle (Sed+Veh); Sed+DOX; exercise + veh (Ex+Veh); and Ex+DOX. Rats in the exercise groups were preconditioned with high intensity interval training consisting of 4x4 minute bouts of exercise at 85-95% of VO2peak separated by 2 minutes of active recovery performed 5 days per week. Exercise was implemented one week prior to the first injection and continued throughout the study. Animals received either DOX (4mg/kg) or veh (saline) intraperitoneal injections bi-weekly for a cumulative dose of 12 mg/kg per animal. Five days following the final injection, animals were anesthetized with isoflurane, decapitated and aortas and perivascular adipose tissue (PVAT) were removed for western blot analyses. No significant differences in aortic protein expression were detected for inducible nitric oxide synthase (iNOS) or the upstream activator of endothelial nitric oxide synthase (eNOS), Akt, across groups (p>0.05), whereas eNOS protein expression was significantly downregulated in Sed+DOX (p=0.003). In contrast, eNOS expression was not altered in Ex+DOX treated animals. Protein expression of iNOS in PVAT was upregulated with exercise in the DOX-treated groups (p=0.039). These findings suggest that exercise preconditioning may help mitigate vascular effects of DOX by preventing downregulation of eNOS in the aorta.
ContributorsO'Neill, Liam Martin (Author) / Sweazea, Karen (Thesis director) / Angadi, Siddhartha (Committee member) / Dickinson, Jared (Committee member) / School of Human Evolution and Social Change (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Estimates indicate that in the United States 1 in 8 women will develop breast cancer in their lifetime. Improved cancer screenings, early detection, and targeted treatments have increased breast cancer survival rates. However, breast cancer patients treated with chemotherapy are at an increased risk for cardiovascular disease, functional impairments, and loss of cardiorespiratory fitness. These negative outcomes have implications for early morbidity and mortality. The purpose of this thesis was to test the hypothesis that high-intensity exercise preconditioning (exercise commenced prior to initiating chemotherapy and continued throughout treatment cycles) preserves health-related outcomes in breast cancer patients treated with anthracycline-containing chemotherapy. Here, we present a subset of preliminary data from an ongoing trial (NCT02842658) that is focused on VO2peak and skeletal muscle outcomes from the first 10 participants that have enrolled in the trial. Breast cancer patients (N=10; 50 ± 11 y; 168 ± 4 cm; 92 ± 37 kg; 32.3 ± 12.3 kg/m2) scheduled to receive anthracycline-containing chemotherapy were randomly assigned to one of two interventions: 1) exercise preconditioning, (3 days per week of supervised exercise throughout treatment) or 2) standard of care (attention-control). Pre-testing occurred 1-2 week prior to chemotherapy. The interventions were initiated 1 week prior to chemotherapy and continued throughout anthracycline treatment. Post-testing occurred 3-7 days following the last anthracycline treatment. VO2peak (L/min) was reduced by 16% in the control group (P < 0.05), whereas VO2peak was preserved in the exercise preconditioning group. Trends for greater preservation and/or improvement in the exercise preconditioning group were also observed for lean body mass and peak heart rate. Hand grip strength was not changed in either group (P > 0.05). Both groups demonstrated an increase in ultrasound-derived echogenicity measures of the vastus lateralis (P < 0.05), indicating changes in the composition of the skeletal muscle during treatment. These preliminary data highlight that exercise preconditioning may serve as a strategy to preserve cardiorespiratory fitness and perhaps lean mass during anthracycline treatment of breast cancer. There remains a need for larger, definitive clinical trials to identify strategies to prevent the array of chemotherapy-induced toxicities that are observed in breast cancer patients treated with anthracyclines.
ContributorsCasey, Kathleen (Author) / Angadi, Siddhartha (Thesis director) / Gaesser, Glenn (Committee member) / Dickinson, Jared (Committee member) / College of Health Solutions (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
College students are a niche of young adults, characterized by abnormal sleeping habits and inactive lifestyles. Many students entering college are as young as 18 years old and graduate by 22 years old, a window of time in which their bones are still accruing mineral. The purpose of this cross-sectional study was to determine whether sleep patterns and physical activity observed in college students (N= 52) 18-25 years old at Arizona State University influenced bone biomarkers, osteocalcin (OC) and N-terminal telopeptide of type 1 collagen (NTX-1) concentrations. Students completed various dietary and health history questionnaires including the International Physical Activity Questionnaire short form. Students wore an actigraphy watch for 7 consecutive nights to record sleep events including total sleep time, sleep onset latency and wake after sleep onset. Total sleep time had a significant, negative correlation with OC (r = -0.298, p-value =0.036) while sleep onset latency had a significant, positive correlation with NTX-1 serum concentration (r = 0.293, p-value = 0.037). Despite correlational findings, only sleep percent was found to be significant (beta coefficient = 0.271 p-value = 0.788) among all the sleep components assessed, after adjusting for gender, race, BMI and calcium intake in multivariate regression models. Physical activity alone was not associated with either bone biomarker. Physical activity*sleep onset latency interactions were significantly correlated with osteocalcin (r = 0.308, p-value =0.006) and NTX-1 (r = 0.286, p-value = 0.042) serum concentrations. Sleep percent*physical activity interactions were significantly correlated with osteocalcin (r = 0.280, p-value = 0.049) but not with NTX-1 serum concentrations. Interaction effects were no longer significant after adjusting for covariates in the regression models. While sleep percent was a significant component in the regression model for NTX-1, it was not clinically significant. Overall, sleep patterns and physical activity did not explain OC and NTX-1 serum concentrations in college students 18-25 years old. Future studies may need to consider objective physical activity devices including accelerometers to measure activity levels. At this time, college students should review sleep and physical activity recommendations to ensure optimal healthy habits are practiced.
ContributorsMahmood, Tara Nabil (Author) / Whisner, Corrie (Thesis advisor) / Dickinson, Jared (Committee member) / Petrov, Megan (Committee member) / Adams, Marc (Committee member) / Arizona State University (Publisher)
Created2019