IU Indianapolis ScholarWorks :: Browsing by Subject "Age"

Browsing by Subject "Age"

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Age-Related Changes in MicroRNA Expression and Pharmacogenes in Human Liver
(Wiley, 2015-08) Burgess, Kimberly S.; Philips, Santosh; Benson, Eric A.; Desta, Zeruesenay; Gaedigk, Andrea; Gaedigk, Roger; Segar, Matthew W.; Liu, Yunlong; Skaar, Todd C.; Department of Pharmacology and Toxicology, IU School of Medicine
Developmental changes in the liver can significantly impact drug disposition. Due to the emergence of microRNAs (miRNAs) as important regulators of drug disposition gene expression, we studied age-dependent changes in miRNA expression. Expression of 533 miRNAs was measured in 90 human liver tissues (fetal, pediatric [1-17 years], and adult [28-80 years]; n = 30 each). In all, 114 miRNAs were upregulated and 72 were downregulated from fetal to pediatric, and 2 and 3, respectively, from pediatric to adult. Among the developmentally changing miRNAs, 99 miRNA-mRNA interactions were predicted or experimentally validated (e.g., hsa-miR-125b-5p-CYP1A1; hsa-miR-34a-5p-HNF4A). In human liver samples (n = 10 each), analyzed by RNA-sequencing, significant negative correlations were observed between the expression of >1,000 miRNAs and mRNAs of drug disposition and regulatory genes. Our data suggest a mechanism for the marked changes in hepatic gene expression between the fetal and pediatric developmental periods, and support a role for these age-dependent miRNAs in regulating drug disposition.
Aging with Traumatic Brain Injury: Deleterious Effects of Injury Chronicity Are Most Pronounced in Later Life
(Mary Ann Liebert, 2021) Rabinowitz, Amanda R.; Kumar, Raj G.; Sima, Adam; Venkatesan, Umesh M.; Juengst, Shannon B.; O’Neil-Pirozzi, Therese M.; Watanabe, Thomas K.; Goldin, Yelena; Hammond, Flora M.; Dreer, Laura E.; Physical Medicine and Rehabilitation, School of Medicine
Understanding the effects of age on longitudinal traumatic brain injury (TBI) outcomes requires attention to both chronic and evolving TBI effects and age-related changes in health and function. The present study examines the independent and interactive effects of aging and chronicity on functional outcomes after TBI. We leveraged a well-defined cohort of individuals who sustained a moderate/severe TBI and received acute inpatient rehabilitation at specialized centers with high follow up rate as part of their involvement in the TBI Model Systems longitudinal study. We selected individuals at one of two levels of TBI chronicity (either 2 or 10 years post-injury) and used an exact matching procedure to obtain balanced chronicity groups based on age and other characteristics (N = 1993). We found that both older age and greater injury chronicity were related to greater disability, reduced functional independence, and less community participation. There was a significant age by chronicity interaction, indicating that the adverse effects of greater time post-injury were most pronounced among survivors who were age 75 or older. The inflection point at roughly 75 years of age was corroborated by post hoc analyses, dividing the sample by age at 75 years and examining the interaction between age group and chronicity. These findings point to a need for provision of rehabilitation services in the chronic injury period, particularly for those who are over 75 years old. Future work should investigate the underlying mechanisms of this interaction towards the goal of developing interventions and models of care to promote healthy aging with TBI.
Cognitive testing in older primary care patients: A cluster-randomized trial
(Elsevier, 2015-09) Fowler, Nicole R.; Morrow, Lisa; Chiappetta, Laurel; Snitz, Beth; Huber, Kimberly; Rodriguez, Eric; Saxton, Judith; Department of Medicine, IU School of Medicine
INTRODUCTION: This study investigated whether neuropsychological testing in primary care (PC) offices altered physician-initiated interventions related to cognitive impairment (CI) or slowed the rate of CI progression. METHODS: This 24-month, cluster-randomized study included 11 community-based PC practices randomized to either treatment as usual (5 practices) or cognitive report (CR; 6 practices) arms. From 2005 to 2008, 533 patients aged ≥65 years and without a diagnosis of CI were recruited; 423 were retested 24 months after baseline. RESULTS: CR physicians were significantly more likely to order cognitive-related interventions (P = .02), document discussions about cognition (P = .003), and order blood tests to rule out reversible CI (P = .002). At follow-up, significantly more CR patients had a medication for cognition listed in their chart (P = .02). There was no difference in the rate of cognitive decline between the groups. DISCUSSION: Providing cognitive information to physicians resulted in higher rates of physician-initiated interventions for patients with CI.
Comparison of Risk Factors for Pediatric Kidney Stone Formation: The Effects of Sex
(Frontiers, 2019-02-12) Schwaderer, Andrew L.; Raina, Rupesh; Khare, Anshika; Safadi, Fayez; Moe, Sharon M.; Kusumi, Kirsten; Pediatrics, School of Medicine
Background: Urinary stones are affecting more children, and pediatric stone formers have unique pathophysiology compared to adults. While adult stone formers are most frequently male, children have an age dependent sex prevalence. Under 10 years, a majority of stone formers are boys; adolescent stone formers are mostly female. Previous adult studies have shown that stone composition is influenced by the sex and age of the stone former. Thus, we hypothesize that female and male stone forming children will also have sex and age specific stone phenotypes. Methods: Retrospective chart review of a large pediatric center's stone forming children 6/1/2009 to 6/1/2016. Patients were identified by ICD 9 codes: N20, N20.1, and N20.9. Charts were reviewed for radiographic evidence of stones or documented visualized stone passage. Results: One hundred and thirty six subjects: 54 males and 82 females. Females were older, median age 14 years [interquartile range (IQR): 11, 15] vs. males' median age 12 years (IQR: 11, 14) (p < 0.01). Females had lower height z-scores, median 0.2 (IQR: -0.8, 0.8) vs. males' median 0.8 (IQR: -0.2, 1.8) (p < 0.01). Presenting symptoms were similar except flank pain affecting 39% of females vs. 22% of males (p = 0.04). Leukocyte esterase was positive in more females than males (33 vs. 4%) (p < 0.001). Males had a higher BUN/Cr ratio, mean ± standard deviation of 19.8 ± 6.3 vs. 16.6 ± 6.5 in females (p = 0.01). Glomerular hyperfiltration was present in 9% of patients while 35% of patients had estimated glomerular filtration rate (eGFR) < 90 ml/min/1.73 m2. Treatment strategies and clinical course were similar except females were told to increase dietary citrate more frequently than males (21 vs. 4%) (p < 0.01). Conclusion: We have provided a novel analysis and demonstrated that low height z-score and pyuria are more common in female stone formers. We have also shown that 9% of pediatric stone formers have labs consistent with hyperfiltration. Whether high protein intake and/or chronic dehydration are associated with hyperfiltration and long-term renal function in children with kidney stones will be an area for future research.
Differences in preoperative frailty assessment of surgical candidates by sex, age, and race
(Elsevier, 2024-05-11) Nicaise, Edouard H.; Palmateer, Gregory; Schmeusser, Benjamin N.; Futral, Cameron; Liu, Yuan; Goyal, Subir; Nabavizadeh, Reza; Kooby, David A.; Maithel, Shishir K.; Sweeney, John F.; Sarmiento, Juan M.; Ogan, Kenneth; Master, Viraj A.; Urology, School of Medicine
Introduction: Surgical decision-making often relies on a surgeon's subjective assessment of a patient's frailty status to undergo surgery. Certain patient demographics can influence subjective judgment when compared to validated objective assessments. In this study, we explore the relationship between subjective and objective frailty assessments according to patient age, sex, and race. Methods: Patients were prospectively enrolled in urology, general surgery, and surgical oncology clinics. Using a visual analog scale (0-100), operating surgeons independently rated the patient's frailty status. Objective frailty was classified using the Fried Frailty Criteria ranging from 0 to 5. Multivariable proportional odds models were conducted to examine the potential association of factors with objective frailty, according to surgeon frailty rating. Subgroup analysis according to patient sex, race, and age was also performed. Results: Seven male surgeons assessed 203 patients preoperatively with a median age of 65. A majority of patients were male (61 %), white (67 %), and 60 % and 40 % underwent urologic and general surgery/surgical oncology procedures respectively. Increased subjective surgeon rating (OR 1.69; p < 0.001) was significantly associated with the presence of objective frailty. On subgroup analysis, a higher magnitude of such association was observed more in females (OR 1.86; p = 0.0007), non-white (OR 1.84; p = 0.0019), and older (>60, OR 1.75; p = 0.0001) patients, compared to male (OR 1.45; p = 0.0243), non-white (OR 1.48; p = 0.0109) and patients under 60 (OR 1.47; p = 0.0823). Conclusion: The surgeon's subjective assessment of frailty demonstrated tendencies to rate older, female, and non-white patients as frail; however, differences in patient sex, age, and race were not statistically significant.
Differential effects of risk factors on the cognitive trajectory of early- and late-onset Alzheimer’s disease
(BMC, 2021-06-14) Kim, Jaeho; Woo, Sook-Young; Kim, Seonwoo; Jang, Hyemin; Kim, Junpyo; Kim, Jisun; Kang, Sung Hoon; Na, Duk L.; Chin, Juhee; Apostolova, Liana G.; Seo, Sang Won; Kim, Hee Jin; Neurology, School of Medicine
Background: Although few studies have shown that risk factors for Alzheimer's disease (AD) are associated with cognitive decline in AD, not much is known whether the impact of risk factors differs between early-onset AD (EOAD, symptom onset < 65 years of age) versus late-onset AD (LOAD). Therefore, we evaluated whether the impact of Alzheimer's disease (AD) risk factors on cognitive trajectories differ in EOAD and LOAD. Methods: We followed-up 193 EOAD and 476 LOAD patients without known autosomal dominant AD mutation for 32.3 ± 23.2 months. Mixed-effects model analyses were performed to evaluate the effects of APOE ε4, low education, hypertension, diabetes, dyslipidemia, and obesity on cognitive trajectories. Results: APOE ε4 carriers showed slower cognitive decline in general cognitive function, language, and memory domains than APOE ε4 carriers in EOAD but not in LOAD. Although patients with low education showed slower cognitive decline than patients with high education in both EOAD and LOAD, the effect was stronger in EOAD, specifically in frontal-executive function. Patients with hypertension showed faster cognitive decline than did patients without hypertension in frontal-executive and general cognitive function in LOAD but not in EOAD. Patients with obesity showed slower decline in general cognitive function than non-obese patients in EOAD but not in LOAD. Conclusions: Known risk factors for AD were associated with slower cognitive decline in EOAD but rapid cognitive decline in LOAD.
Distinctive Features and Outcomes of Hepatocellular Carcinoma in Patients With Alcohol-Related Liver Disease: A US Multicenter Study
(Wolters Kluwer Health, 2020-03) deLemos, Andrew; Patel, Milin; Gawrieh, Samer; Burney, Heather; Dakhoul, Lara; Miller, Ethan; Scanga, Andrew; Kettler, Carla; Liu, Hao; Roche, Patrick; Wattacheril, Julia; Chalasani, Naga; Medicine, School of Medicine
Introduction: The burden of hepatocellular carcinoma (HCC) occurring in patients with alcoholic liver disease (ALD) is increasing at an alarming rate. The aims of this study were to compare the patient and tumor characteristics of HCC occurring in ALD-alone relative to and in addition to other chronic liver diseases. Methods: Patients diagnosed with HCC between 2000 and 2014 were identified at 5 US clinical centers. The patients were categorized as ALD-alone, ALD plus viral hepatitis, or a non-ALD etiology. Clinical and tumor characteristics among the 3 groups were compared, and survival probability was estimated by the Kaplan-Meier method. The frequency of noncirrhotic HCC was compared across the 3 groups. Results: A total of 5,327 patients with HCC were analyzed. Six hundred seventy (12.6%) developed HCC due to underlying ALD. Ninety-one percent of ALD-related HCC arose in men, in contrast to non-ALD etiologies where men accounted for 70% of HCCs cases (P < 0.001). Patients with ALD-alone-related HCC were older at diagnosis and had tumors less likely to be detected as part of routine surveillance. The ALD-alone cohort was least likely to be within the Milan criteria and to undergo liver transplantation. Overall survival in the ALD-alone HCC cohort was lower than the other 2 groups (1.07 vs 1.31 vs 1.41 years, P < 0.001). HCC in the noncirrhotic ALD cohorts occurred in only 3.5% of the patients compared with 15.7% in patients with non-ALD etiologies (P < 0.001). Discussion: HCC occurring in patients with ALD occurred mostly in older men and almost exclusively in a cirrhotic background. They present with advanced tumors, and their survival is lower than HCCs occurring in non-ALD.
Freedom from Recurrence across Age in Non-Melanoma Skin Cancer Treated with Image-Guided Superficial Radiation Therapy
(MDPI, 2024-09-05) Farberg, Aaron S.; Heysek, Randy V.; Haber, Robert; Agha, Rania; Crawford, Kevin M.; Xinge, Ji; Stricker, Jeffrey Blake; Dermatology, School of Medicine
Non-melanoma skin cancers (NMSCs) are a significant cause of morbidity and mortality; their incidence is increasing most in older patients. NMSCs have traditionally been treated with surgical excision, curettage, Mohs micrographic surgery (MMS), and superficial radiotherapy (SRT). Image-guided SRT (IGSRT) is a treatment option for poor surgical candidates or patients with low- or high-risk, early-stage NMSC who prefer to avoid surgery. This large retrospective cohort study compared 2-, 4-, and 6-year freedom from recurrence in biopsy-proven NMSC lesions treated with IGSRT (n = 20,069 lesions) between patients aged < 65 years (n = 3158 lesions) and ≥65 years (n = 16,911 lesions). Overall freedom from recurrence rates were 99.68% at 2 years, 99.57% at 4 years, and 99.57% at 6 years. Rates did not differ significantly by age (p = 0.8) nor by sex among the two age groups (p > 0.9). There was a significant difference in recurrence among older patients when analyzed by stage (p = 0.032), but no difference by stage in younger patients (p = 0.7). For early-stage NMSCs, IGSRT is a clinically equivalent alternative to MMS and statistically significant in superiority to non-image-guided SRT. This study demonstrates that there is no significant effect of age on 2-, 4-, or 6-year freedom from recurrence in patients with IGSRT-treated NMSC.
The influence of body mass index and age on C-peptide at the diagnosis of type 1 diabetes in children who participated in the diabetes prevention trial-type 1
(Wiley, 2018-05) Sosenko, Jay M.; Geyer, Susan; Skyler, Jay S.; Rafkin, Lisa E.; Ismail, Heba M.; Libman, Ingrid M.; Liu, Yuk-Fun; DiMeglio, Linda A.; Evans-Molina, Carmella; Palmer, Jerry P.; Medicine, School of Medicine
BACKGROUND/OBJECTIVE: The extent of influence of BMI and age on C-peptide at the diagnosis of type 1 diabetes (T1D) is unknown. We thus studied the impact of body mass index Z-scores (BMIZ) and age on C-peptide measures at and soon after the diagnosis of T1D. METHODS: Data from Diabetes Prevention Trial-Type 1 (DPT-1) participants <18.0 years at diagnosis was analyzed. Analyses examined associations of C-peptide measures with BMIZ and age in 2 cohorts: oral glucose tolerance tests (OGTTs) at diagnosis (n = 99) and mixed meal tolerance tests (MMTTs) <6 months after diagnosis (n = 80). Multivariable linear regression was utilized. RESULTS: Fasting and area under the curve (AUC) C-peptide from OGTTs (n = 99) at diagnosis and MMTTs (n = 80) after diagnosis were positively associated with BMIZ and age (P < .001 for all). Associations persisted when BMIZ and age were included as independent variables in regression models (P < .001 for all). BMIZ and age explained 31%-47% of the variance of C-peptide measures. In an example, 2 individuals with identical AUC C-peptide values had an approximate 5-fold difference in values after adjustments for BMIZ and age. The association between fasting glucose and C-peptide decreased markedly when fasting C-peptide values were adjusted (r = 0.30, P < .01 to r = 0.07, n.s.). CONCLUSIONS: C-peptide measures are strongly and independently related to BMIZ and age at and soon after the diagnosis of T1D. Adjustments for BMIZ and age cause substantial changes in C-peptide values, and impact the association between glycemia and C-peptide. Such adjustments can improve assessments of β-cell impairment at diagnosis.
The Influence of Health Care Professional Characteristics on Pain Management Decisions
(Oxford Academic, 2015-01) Bartley, Emily J.; Boissoneault, Jeff; Vargovich, Alison M.; Wandner PhD, Laura D.; Hirsh, Adam T.; Lok, Benjamin C.; Heft, Marc W.; Robinson, Michael E.; Psychology, School of Science
Objective Evidence suggests that patient characteristics such as sex, race, and age influence the pain management decisions of health care providers. Although this signifies that patient demographics may be important determinants of health care decisions, pain-related care also may be impacted by the personal characteristics of the health care practitioner. However, the extent to which health care provider characteristics affect pain management decisions is unclear, underscoring the need for further research in this area. Methods A total of 154 health care providers (77 physicians, 77 dentists) viewed video vignettes of virtual human (VH) patients varying in sex, race, and age. Practitioners provided computerized ratings of VH patients’ pain intensity and unpleasantness, and also reported their willingness to prescribe non-opioid and opioid analgesics for each patient. Practitioner sex, race, age, and duration of professional experience were included as predictors to determine their impact on pain management decisions. Results When assessing and treating pain, practitioner sex, race, age, and duration of experience were all significantly associated with pain management decisions. Further, the role of these characteristics differed across VH patient sex, race, and age. Conclusions These findings suggest that pain assessment and treatment decisions may be impacted by the health care providers’ demographic characteristics, effects which may contribute to pain management disparities. Future research is warranted to determine whether findings replicate in other health care disciplines and medical conditions, and identify other practitioner characteristics (e.g., culture) that may affect pain management decisions.

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