IU Indianapolis ScholarWorks :: Browsing by Subject "Risk Factors"

Browsing by Subject "Risk Factors"

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Associations of Muscle Mass and Strength with All-Cause Mortality among US Older Adults
(Lippincott, Williams & Wilkins, 2018-03) Li, Ran; Xia, Jin; Zhang, Xi; Gathirua-Mwangi, Wambui Grace; Guo, Jianjun; Li, Yufeng; McKenzie, Steve; Song, Yiqing; Epidemiology, School of Public Health
INTRODUCTION: Recent studies suggested that muscle mass and muscle strength may independently or synergistically affect aging-related health outcomes in older adults; however, prospective data on mortality in the general population are sparse. METHODS: We aimed to prospectively examine individual and joint associations of low muscle mass and low muscle strength with all-cause mortality in a nationally representative sample. This study included 4449 participants age 50 yr and older from the National Health and Nutrition Examination Survey 1999 to 2002 with public use 2011 linked mortality files. Weighted multivariable logistic regression models were adjusted for age, sex, race, body mass index (BMI), smoking, alcohol use, education, leisure time physical activity, sedentary time, and comorbid diseases. RESULTS: Overall, the prevalence of low muscle mass was 23.1% defined by appendicular lean mass (ALM) and 17.0% defined by ALM/BMI, and the prevalence of low muscle strength was 19.4%. In the joint analyses, all-cause mortality was significantly higher among individuals with low muscle strength, whether they had low muscle mass (odds ratio [OR], 2.03; 95% confidence interval [CI], 1.27-3.24 for ALM; OR, 2.53; 95% CI, 1.64-3.88 for ALM/BMI) or not (OR, 2.66; 95% CI, 1.53-4.62 for ALM; OR, 2.17; 95% CI, 1.29-3.64 for ALM/BMI). In addition, the significant associations between low muscle strength and all-cause mortality persisted across different levels of metabolic syndrome, sedentary time, and LTPA. CONCLUSIONS: Low muscle strength was independently associated with elevated risk of all-cause mortality, regardless of muscle mass, metabolic syndrome, sedentary time, or LTPA among US older adults, indicating the importance of muscle strength in predicting aging-related health outcomes in older adults.
Biological Hallmarks of Cancer in Alzheimer’s Disease
(Elsevier, 2019-04-16) Nudelman, Kelly N. H.; McDonald, Brenna C.; Lahiri, Debomoy K.; Saykin, Andrew J.; Medical and Molecular Genetics, School of Medicine
Although Alzheimer’s disease (AD) is an international health research priority for our aging population, little therapeutic progress has been made. This lack of progress may be partially attributable to disease heterogeneity. Previous studies have identified an inverse association of cancer and AD, suggesting that cancer history may be one source of AD heterogeneity. These findings are particularly interesting in light of the number of common risk factors and two-hit models hypothesized to commonly drive both diseases. We reviewed the ten hallmark biological alterations of cancer cells to investigate overlap with the AD literature and identified overlap of all ten hallmarks in AD, including: 1) potentially common underlying risk factors, such as increased inflammation, deregulated cellular energetics, and genome instability, 2) inversely regulated mechanisms, including cell death and evading growth suppressors, and 3) functions with more complex, pleiotropic mechanisms, some of which may be stage-dependent in AD, such as cell adhesion/contact inhibition and angiogenesis. Additionally, we discuss the recent observation of a biological link between cancer and AD neuropathology. Finally, we address the therapeutic implications of this topic. The significant overlap of functional pathways and molecules between these diseases, some similarly and some oppositely regulated or functioning in each disease, supports the need for more research to elucidate cancer-related AD genetic and functional heterogeneity, with the aims of better understanding AD risk mediators, as well as further exploring the potential for some types of drug repurposing towards AD therapeutic development.
Child and Infant Mortality; Risk Factors Related to SUID in Marion County
(Office of the Vice Chancellor for Research, 2015-04-17) Oberle, Morgan R.; Elomba, Charles D.; Cullen, Deborah L.; Stiffler, Deborah J.
Between 2003- 2012, Indiana had 434 child deaths, including 53 Sudden Unexpected Infant Death (SUID) cases. Marion County has a high rate of SUID at 14%. The purpose of our research is to identify the risk factors for suffocation and to determine if SUID can be better prevented. In a pilot exploratory study, we analyzed five de-identified Marion County SUID cases to identify the asphyxia variables. The Fetal Infant Mortality Review (FIMR) cases allowed for thematic analysis. We used a meta-aggregation program NOTARI (Narrative, opinion, text assessment, and review instrument) to focus on categorical variables. Results identified asphyxia variables such as swaddling, blanket suffocation, wedging, parents bedding, soft bedding with pillows. Common maternal variables were obesity, hypertension, and STDs. Infant variables included breathing problems and cardio-respiratory pathologies. We found four cases with documented safe sleep education. The education that parents receive on safe sleep is not a guarantee that they will practice safe sleep with their infants. The education might not be effective enough to help them comprehend its importance; therefore nurses and other healthcare professionals need to consider changing the way they educate and advocate for parents. We suggest the introduction of more primary educational programs that will help the community understand safe sleep and SUID. This intervention would help decrease the incidence of sudden unexpected infant death.
Clinical and Laboratory characteristics of patients with COVID-19 Infection and Deep Venous Thrombosis
(Elsevier, 2020-10-22) Motaganahalli, Raghu L.; Kapoor, Rajat; Timsina, Lava R.; Gutwein, Ashley R.; Ingram, Michael D.; Raman, Subha; Roberts, Scott D.; Rahman, Omar; Rollins, David; Dalsing, Michael C.; Surgery, School of Medicine
Objective: Early reports suggest that patients with novel coronavirus disease-2019 (COVID-19) infection carry a significant risk of altered coagulation with an increased risk for venous thromboembolic events. This report investigates the relationship of significant COVID-19 infection and deep venous thrombosis (DVT) as reflected in the patient clinical and laboratory characteristics. Methods: We reviewed the demographics, clinical presentation, laboratory and radiologic evaluations, results of venous duplex imaging and mortality of COVID-19-positive patients (18-89 years) admitted to the Indiana University Academic Health Center. Using oxygen saturation, radiologic findings, and need for advanced respiratory therapies, patients were classified into mild, moderate, or severe categories of COVID-19 infection. A descriptive analysis was performed using univariate and bivariate Fisher's exact and Wilcoxon rank-sum tests to examine the distribution of patient characteristics and compare the DVT outcomes. A multivariable logistic regression model was used to estimate the adjusted odds ratio of experiencing DVT and a receiver operating curve analysis to identify the optimal cutoff for d-dimer to predict DVT in this COVID-19 cohort. Time to the diagnosis of DVT from admission was analyzed using log-rank test and Kaplan-Meier plots. Results: Our study included 71 unique COVID-19-positive patients (mean age, 61 years) categorized as having 3% mild, 14% moderate, and 83% severe infection and evaluated with 107 venous duplex studies. DVT was identified in 47.8% of patients (37% of examinations) at an average of 5.9 days after admission. Patients with DVT were predominantly male (67%; P = .032) with proximal venous involvement (29% upper and 39% in the lower extremities with 55% of the latter demonstrating bilateral involvement). Patients with DVT had a significantly higher mean d-dimer of 5447 ± 7032 ng/mL (P = .0101), and alkaline phosphatase of 110 IU/L (P = .0095) than those without DVT. On multivariable analysis, elevated d-dimer (P = .038) and alkaline phosphatase (P = .021) were associated with risk for DVT, whereas age, sex, elevated C-reactive protein, and ferritin levels were not. A receiver operating curve analysis suggests an optimal d-dimer value of 2450 ng/mL cutoff with 70% sensitivity, 59.5% specificity, and 61% positive predictive value, and 68.8% negative predictive value. Conclusions: This study suggests that males with severe COVID-19 infection requiring hospitalization are at highest risk for developing DVT. Elevated d-dimers and alkaline phosphatase along with our multivariable model can alert the clinician to the increased risk of DVT requiring early evaluation and aggressive treatment
COVID-19s Impact on the Hispanic Community: How Understanding Culture Can Improve Outcomes
(Indiana Medical Student Program for Research and Scholarship (IMPRS), 2020-12-15) Guerra Rodriguez, Yamilet; Hudson, Brenda L.; IU School of Medicine
Background: A disproportionate burden of SARS-Cov-2 infection, or coronavirus disease 2019 (Covid-19), and death are highest among racial and ethnic minority groups. Based on data available on June 12, 2020, Hispanic people are more likely to acquire COVID-19 and have higher incidence of hospitalization and death compared to their white, non-Hispanic counterparts. While this issue is complex, many have hypothesized that the difference is due to societal factors and communication methods. The aim of this project was to evaluate information related to how the Hispanic population is affected by COVID-19 and how communications about the disease should be designed based on past research, physician input, and cultural sensitivities. Methods: We conducted a thorough literature search on COVID-19 articles, both peer reviewed and grey literature, evaluating race and ethnic differences in disease prevalence and severity. Additionally, we conducted interviews with a small number of Indiana doctors who treat Hispanic patients to obtain a doctor’s perspective on the Hispanic community’s needs during the pandemic and ways to help reduce prevalence. Results: Physicians in Indiana believe the main approach to help the Hispanic community is by utilizing trusted community resources to communicate information and build relationships with patients over time. It is recommended to develop new methods to deliver essential information about COVID-19 through multiple mediums, in a clear way, and in Spanish with focus on the collective good of the family. In addition, it is important not to just translate resources from English to Spanish but to design materials addressing barriers specific to the Hispanic community. Conclusion: More culturally tailored information should be released to educate the Hispanic community about COVID-19. This information will assist in the design of materials and initiatives for the Hispanic community that we hope will improve methods of communication and care delivery related to COVID-19.
Diabetes and peripheral arterial disease in men: trends in prevalence, mortality, and effect of concomitant coronary disease
(Wiley, 2009-08) Kamalesh, Masoor; Shen, Jianzhao; Biostatistics, School of Public Health
BACKGROUND: Recent data on trends in diabetes mellitus (DM) prevalence and long-term effect on mortality in peripheral arterial disease (PAD) subjects is lacking. METHODS: All subjects discharged from any VA medical center between October 1990 to September 1997 with an International Classification of Diseases (ICD)-9 code for PAD and DM in the discharge summary were retrospectively identified. Demographic data were extracted from the database. Mortality data were obtained from the Beneficiary Information and Resource Locator. Outcome measures were age specific DM prevalence over time, and short-term and long-term mortality. RESULTS: Of 33, 629 patients with PAD, 9474 (29%) had DM. Diabetes mellitus subjects were less likely to be white and had more comorbidities. Mean length of hospital stay was greater for DM (22.3 d vs 18.7 days, P < 0.001). Mortality was higher for DM at 180 days (9.8% vs 8.4%, P < 0.001), 1 year (16.4% vs 13.7%, P < 0.001), and continues to increase at 8 years of follow-up. Logistic regression analysis showed no interaction between DM and coronary artery disease (CAD). CONCLUSIONS: Diabetes mellitus increases all-cause mortality in subjects with PAD starting at 6 months post-discharge and continues to be higher even at 8 years of follow-up. There was a lack of interaction of DM and CAD on mortality in this cohort of subjects with PAD.
Effects of Risk Factors on Belizean Adolescents’ Academic Behaviors and Grit after Prolonged Absence During the COVID-19 Pandemic
(Ubiquity Press, 2022-06-17) Vairez, Mathias, Jr.; Gomez, Frank, Jr.; Gentle-Genitty, Carolyn; Quiroz, Janeen; Manzanero, Olga; School of Social Work
This causal-comparative study explored the effects of risk factors—family status, parental marital status, family income, and parent education level—on Belizean adolescents’ academic behaviors and grit (passion and perseverance in goal achievement) following prolonged absence during the COVID-19 pandemic. Data were collected online using a demographic survey, the Grit-S Scale (Duckworth & Quinn, 2009), coupled with eight additional items to measure academic behaviors (attendance, preparedness, attention, note-taking, participation, organization, use of out-of-school time, and homework completion and submission) for success (Farrington et al., 2012) from secondary and tertiary students in Belize. With rare exception, Belizean education took place in person before the pandemic. This changed to remote teaching and learning during the pandemic. Findings showed that adolescents from the defined risk factor of single-parent households experienced greater declines across all eight academic behaviors. Additionally, this effect was more pronounced for adolescents who experienced the loss of a parent from divorce or death of a parent. For grit, there were two key outcomes: (a) adolescents from nuclear and higher income families had slightly higher levels of grit; and (b) adolescents from parents with lower educational attainment had significantly higher levels of grit than their peers. Based on these findings, recommendations include more study of schools that invest in becoming trauma responsive when evaluating engagement and performance during prolonged absences. Future research should assess adolescents’ level of academic behaviors, grit, and other noncognitive factors.
Exploratory genome-wide interaction analysis of non-steroidal anti-inflammatory drugs and predicted gene expression on colorectal cancer risk
(American Association for Cancer Research, 2020-09) Wang, Xiaoliang; Su, Yu-Ru; Petersen, Paneen S.; Bien, Stephanie; Schmit, Stephanie L.; Drew, David A.; Albanes, Demetrius; Berndt, Sonja I.; Brenner, Hermann; Campbell, Peter T.; Casey, Graham; Chang-Claude, Jenny; Gallinger, Steven J.; Gruber, Stephen B.; Haile, Robert W.; Harrison, Tabitha A.; Hoffmeister, Michael; Jacobs, Eric J.; Jenkins, Mark A.; Joshi, Amit D.; Li, Li; Lin, Yi; Lindor, Noralane M.; Le Marchand, Loïc; Martin, Vicente; Milne, Roger; Maclnnis, Robert; Moreno, Victor; Nan, Hongmei; Newcomb, Polly A.; Potter, John D.; Rennert, Gad; Rennert, Hedy; Slattery, Martha L.; Thibodeau, Steve N.; Weinstein, Stephanie J.; Woods, Michael O.; Chan, Andrew T.; White, Emily; Hsu, Li; Peters, Ulrike; Global Health, School of Public Health
Background: Regular use of nonsteroidal anti-inflammatory drugs (NSAID) is associated with lower risk of colorectal cancer. Genome-wide interaction analysis on single variants (G × E) has identified several SNPs that may interact with NSAIDs to confer colorectal cancer risk, but variations in gene expression levels may also modify the effect of NSAID use. Therefore, we tested interactions between NSAID use and predicted gene expression levels in relation to colorectal cancer risk. Methods: Genetically predicted gene expressions were tested for interaction with NSAID use on colorectal cancer risk among 19,258 colorectal cancer cases and 18,597 controls from 21 observational studies. A Mixed Score Test for Interactions (MiSTi) approach was used to jointly assess G × E effects which are modeled via fixed interaction effects of the weighted burden within each gene set (burden) and residual G × E effects (variance). A false discovery rate (FDR) at 0.2 was applied to correct for multiple testing. Results: Among the 4,840 genes tested, genetically predicted expression levels of four genes modified the effect of any NSAID use on colorectal cancer risk, including DPP10 (PG×E = 1.96 × 10-4), KRT16 (PG×E = 2.3 × 10-4), CD14 (PG×E = 9.38 × 10-4), and CYP27A1 (PG×E = 1.44 × 10-3). There was a significant interaction between expression level of RP11-89N17 and regular use of aspirin only on colorectal cancer risk (PG×E = 3.23 × 10-5). No interactions were observed between predicted gene expression and nonaspirin NSAID use at FDR < 0.2. Conclusions: By incorporating functional information, we discovered several novel genes that interacted with NSAID use.
Factors Associated With Death in Critically Ill Patients With Coronavirus Disease 2019 in the US
(American Medical Association, 2020-07-15) Gupta, Shruti; Hayek, Salim S.; Wang, Wei; Chan, Lili; Mathews, Kusum S.; Melamed, Michal L.; Brenner, Samantha K.; Leonberg-Yoo, Amanda; Schenck, Edward J.; Radbel, Jared; Reiser, Jochen; Bansal, Anip; Srivastava, Anand; Zhou, Yan; Sutherland, Anne; Green, Adam; Shehata, Alexandre M.; Goyal, Nitender; Vijayan, Anitha; Velez, Juan Carlos Q.; Shaefi, Shahzad; Parikh, Chirag R.; Arunthamakun, Justin; Athavale, Ambarish M.; Friedman, Allon N.; Short, Samuel A. P.; Kibbelaar, Zoe A.; Omar, Samah Abu; Admon, Andrew J.; Donnelly, John P.; Gershengorn, Hayley B.; Hernán, Miguel A.; Semler, Matthew W.; Leaf, David E.; Medicine, School of Medicine
Importance: The US is currently an epicenter of the coronavirus disease 2019 (COVID-19) pandemic, yet few national data are available on patient characteristics, treatment, and outcomes of critical illness from COVID-19. Objectives: To assess factors associated with death and to examine interhospital variation in treatment and outcomes for patients with COVID-19. Design, Setting, and Participants: This multicenter cohort study assessed 2215 adults with laboratory-confirmed COVID-19 who were admitted to intensive care units (ICUs) at 65 hospitals across the US from March 4 to April 4, 2020. Exposures: Patient-level data, including demographics, comorbidities, and organ dysfunction, and hospital characteristics, including number of ICU beds. Main Outcomes and Measures: The primary outcome was 28-day in-hospital mortality. Multilevel logistic regression was used to evaluate factors associated with death and to examine interhospital variation in treatment and outcomes. Results: A total of 2215 patients (mean [SD] age, 60.5 [14.5] years; 1436 [64.8%] male; 1738 [78.5%] with at least 1 chronic comorbidity) were included in the study. At 28 days after ICU admission, 784 patients (35.4%) had died, 824 (37.2%) were discharged, and 607 (27.4%) remained hospitalized. At the end of study follow-up (median, 16 days; interquartile range, 8-28 days), 875 patients (39.5%) had died, 1203 (54.3%) were discharged, and 137 (6.2%) remained hospitalized. Factors independently associated with death included older age (≥80 vs <40 years of age: odds ratio [OR], 11.15; 95% CI, 6.19-20.06), male sex (OR, 1.50; 95% CI, 1.19-1.90), higher body mass index (≥40 vs <25: OR, 1.51; 95% CI, 1.01-2.25), coronary artery disease (OR, 1.47; 95% CI, 1.07-2.02), active cancer (OR, 2.15; 95% CI, 1.35-3.43), and the presence of hypoxemia (Pao2:Fio2<100 vs ≥300 mm Hg: OR, 2.94; 95% CI, 2.11-4.08), liver dysfunction (liver Sequential Organ Failure Assessment score of 2 vs 0: OR, 2.61; 95% CI, 1.30–5.25), and kidney dysfunction (renal Sequential Organ Failure Assessment score of 4 vs 0: OR, 2.43; 95% CI, 1.46–4.05) at ICU admission. Patients admitted to hospitals with fewer ICU beds had a higher risk of death (<50 vs ≥100 ICU beds: OR, 3.28; 95% CI, 2.16-4.99). Hospitals varied considerably in the risk-adjusted proportion of patients who died (range, 6.6%-80.8%) and in the percentage of patients who received hydroxychloroquine, tocilizumab, and other treatments and supportive therapies. Conclusions and Relevance: This study identified demographic, clinical, and hospital-level risk factors that may be associated with death in critically ill patients with COVID-19 and can facilitate the identification of medications and supportive therapies to improve outcomes.
Functional variants in the LRRK2 gene confer shared effects on risk for Crohn's disease and Parkinson's disease
(American Association for the Advancement of Science, 2018-01-10) Hui, Ken Y.; Fernandez-Hernandez, Heriberto; Hu, Jianzhong; Schaffner, Adam; Pankratz, Nathan; Hsu, Nai-Yun; Chuang, Ling-Shiang; Carmi, Shai; Villaverde, Nicole; Li, Xianting; Rivas, Manual; Levine, Adam P.; Bao, Xiuliang; Labrias, Philippe R.; Haritunians, Talin; Ruane, Darren; Gettler, Kyle; Chen, Ernie; Li, Dalin; Schiff, Elena R.; Pontikos, Nikolas; Barzilai, Nir; Brant, Steven R.; Bressman, Susan; Cheifetz, Adam S.; Clark, Lorraine N.; Daly, Mark J.; Desnick, Robert J.; Duerr, Richard H.; Katz, Seymour; Lencz, Todd; Myers, Richard H.; Ostrer, Harry; Ozelius, Laurie; Payami, Haydeh; Peter, Yakov; Rioux, John D.; Segal, Anthony W.; Scott, William K.; Silverberg, Mark S.; Vance, Jeffery M.; Ubarretxena-Belandia, Iban; Foroud, Tatiana; Atzmon, Gil; Pe’er, Itsik; Ioannou, Yiannis; McGovern, Dermot P.B.; Yue, Zhenyu; Schadt, Eric E.; Cho, Judy H.; Peter, Inga; Medical and Molecular Genetics, School of Medicine
Crohn's disease (CD), a form of inflammatory bowel disease, has a higher prevalence in Ashkenazi Jewish than in non-Jewish European populations. To define the role of nonsynonymous mutations, we performed exome sequencing of Ashkenazi Jewish patients with CD, followed by array-based genotyping and association analysis in 2066 CD cases and 3633 healthy controls. We detected association signals in the LRRK2 gene that conferred risk for CD (N2081D variant, P = 9.5 × 10-10) or protection from CD (N551K variant, tagging R1398H-associated haplotype, P = 3.3 × 10-8). These variants affected CD age of onset, disease location, LRRK2 activity, and autophagy. Bayesian network analysis of CD patient intestinal tissue further implicated LRRK2 in CD pathogenesis. Analysis of the extended LRRK2 locus in 24,570 CD cases, patients with Parkinson's disease (PD), and healthy controls revealed extensive pleiotropy, with shared genetic effects between CD and PD in both Ashkenazi Jewish and non-Jewish cohorts. The LRRK2 N2081D CD risk allele is located in the same kinase domain as G2019S, a mutation that is the major genetic cause of familial and sporadic PD. Like the G2019S mutation, the N2081D variant was associated with increased kinase activity, whereas neither N551K nor R1398H variants on the protective haplotype altered kinase activity. We also confirmed that R1398H, but not N551K, increased guanosine triphosphate binding and hydrolyzing enzyme (GTPase) activity, thereby deactivating LRRK2. The presence of shared LRRK2 alleles in CD and PD provides refined insight into disease mechanisms and may have major implications for the treatment of these two seemingly unrelated diseases.

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