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Item (506) The complex relationship between pain intensity and physical functioning in fibromyalgia: the mediating role of depression(The Journal of Pain, 2016) Steiner, Jennifer L.; Bigatti, Silvia M.; Slaven, James E.; Ang, Dennis C.Fibromyalgia (FM) is typically associated with the experience of diffuse pain and physical impairment. Depression also commonly co-exists in patients with FM, and it has been correlated with pain intensity and physical functioning. Previous research suggests an association between pain intensity and physical functioning; however, the direct causal relationship between improvements in pain intensity and in functioning is not observed in many FM patients. This may suggest that another factor such as depression is mediating this relationship. The present work examined the possibility of a mediating role of depression in the relationship between pain intensity and functioning over the course of time. 216 patients with FM completed self-report measures of pain intensity, depression, and physical impairment as part of a larger longitudinal study which investigated interventions to increase physical activity among FM patients. Assessments were completed at baseline, 12 weeks, 24 weeks, and 36 weeks. Longitudinal mediational analyses indicated that depression is a statistically significant partial mediator of the relationship between pain intensity and self-reported physical functioning at all four assessment points. To the authors’ knowledge, this is the first study to explicitly examine this relationship in a sample of FM patients, as well as the first to do so using a longitudinal design; this may significantly add to our understanding of the complexities behind creating improvements in physical functioning in this population. Clinical implication for these findings include focusing on depression and psychological correlates of depression as first line therapeutic targets in improving physical functioning of patients with FM, and treating co-morbid depression in patients with fibromyalgia earlier in the course of treatment to prevent engagement in and the perpetuation of the cycle of disability. This work was a secondary data analysis from a study funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases.Item Admission plasma uromodulin and the risk of acute kidney injury in hospitalized patients with cirrhosis: a pilot study(American Physiological Society, 2019-10-01) Patidar, Kavish R.; Garimella, Pranav S.; Macedo, Etienne; Slaven, James E.; Ghabril, Marwan S.; Weber, Regina E.; Anderson, Melissa; Orman, Eric S.; Nephew, Lauren D.; Desai, Archita P.; Chalasani, Naga P.; El-Achkar, Tarek M.; Medicine, School of MedicineAcute kidney injury (AKI) is a common complication in hospitalized patients with cirrhosis. Uromodulin, a protein uniquely produced by the kidney and released both in the urine and circulation, has been shown to regulate AKI and is linked to tubular reserve. Although low levels of urine uromodulin are associated with AKI after cardiac surgery, it is unclear whether circulating uromodulin can stratify the risk of AKI, particularly in a susceptible population such as hospitalized patients with cirrhosis. Thus, we investigated whether plasma uromodulin measured at the time of admission is associated with subsequent hospital-acquired AKI (defined by a rise in serum creatinine >0.3mg/dL within 48 h or ≥ 1.5 times baseline) in patients with cirrhosis. A total of 98 patients [mean age 54 yr, Model for Endstage Liver Disease Sodium (MELD-Na) score 19, and baseline creatinine of 0.95 mg/dL] were included, of which 13% (n = 13) developed AKI. Median uromodulin levels were significantly lower in patients who developed AKI compared with patients who did not (9.30 vs. 13.35 ng/mL, P = 0.02). After adjusting for age, sex, diabetes, hypertension, albumin, and MELD-Na score as covariates on multivariable logistic regression, uromodulin was independently associated with AKI [odd ratios of 1.19 (95% confidence interval 1.02, 1.37; P = 0.02)]. Lower uromodulin levels on admission are associated with increased odds of subsequent AKI in hospitalized patients with cirrhosis. Further studies are needed to better understand the role of uromodulin in the pathogenesis and as a predictive biomarker of AKI in this population. NEW & NOTEWORTHY In this study, we found that admission plasma uromodulin levels are significantly lower in patients who developed subsequent acute kidney injury (AKI) during their hospital stay compared with patients who did not. Additionally, uromodulin is independently associated with AKI development after adjusting for clinically relevant parameters such as age, sex, diabetes, hypertension, severity of cirrhosis, and kidney function. To our knowledge, this is the first study linking plasma uromodulin with AKI development in patients with cirrhosis.Item Alcohol Use Trajectories after High School Graduation among Emerging Adults with Type 1 Diabetes(Elsevier, 2014-08) Hanna, Kathleen M.; Stupiansky, Nathan W.; Weaver, Michael T.; Slaven, James E.; Stump, Timothy E.; IU School of NursingObjective Explore alcohol involvement trajectories and associated factors during the year post-high school (HS) graduation among emerging adults with type 1 diabetes. Methods Youth (N=181) self-reported alcohol use at baseline and every 3 months for 1 year post-HS graduation. Data were also collected on parent-youth conflict, diabetes self-efficacy, major life events, living and educational situations, diabetes management, marijuana use, cigarette smoking, and glycemic control. Trajectories of alcohol use were modeled using latent class growth analysis. Associations between trajectory class and specific salient variables were examined using analysis of variance, chi square, or generalized linear mixed model, as appropriate. Results Identified alcohol involvement trajectory classes were labeled as: 1) Consistent Involvement Group (n=25, 13.8%) with stable, high use relative to other groups over the 12 months; 2) Growing Involvement Group (n=55, 30.4%) with increasing use throughout the 12 months; and 3) Minimal Involvement Group (n=101, 55.8%) with essentially no involvement until month nine. Those with minimal involvement had the best diabetes management and better diabetes self-efficacy than those with consistent involvement. In comparison to those minimally involved, those with growing involvement were more likely to live independently of parents; those consistently involved had more major life events; and both the growing and consistent involvement groups were more likely to have tried marijuana and cigarettes. Conclusions This sample of emerging adults with type 1 diabetes has 3 unique patterns of alcohol use during the first year after high school. Implication and Contribution Among youth with type 1 diabetes in the year post-HS graduation, alcohol involvement knowledge was extended by identifying patterns of such use. Further research of alcohol use patterns is needed to guide health care professionals in their assessments and researchers in testing interventions that target unique patterns.Item Assessing the impact of a primary care electronic medical record system in three Kenyan rural health centers(Oxford University Press, 2016-05) Tierney, William M.; Sidle, John E.; Diero, Lameck O.; Sudoi, Allan; Kiplagat, Jepchirchir; Macharia, Stephen; Shen, Changyu; Yeung, Ada; Were, Martin C.; Slaven, James E.; Wools-Kaloustian, Kara; Medicine, School of MedicineObjective: Efficient, effective health care requires rapid availability of patient information. We designed, implemented, and assessed the impact of a primary care electronic medical record (EMR) in three rural Kenyan health centers. Method: Local clinicians identified data required for primary care and public health reporting. We designed paper encounter forms to capture these data in adult medicine, pediatric, and antenatal clinics. Encounter form data were hand-entered into a new primary care module in an existing EMR serving onsite clinics serving patients infected with the human immunodeficiency virus (HIV). Before subsequent visits, Summary Reports were printed containing selected patient data with reminders for needed HIV care. We assessed effects on patient flow and provider work with time-motion studies before implementation and two years later, and we surveyed providers' satisfaction with the EMR. Results: Between September 2008 and December 2011, 72 635 primary care patients were registered and 114 480 encounter forms were completed. During 2011, 32 193 unique patients visited primary care clinics, and encounter forms were completed for all visits. Of 1031 (3.2%) who were HIV-infected, 85% received HIV care. Patient clinic time increased from 37 to 81 min/visit after EMR implementation in one health center and 56 to 106 min/visit in the other. However, outpatient visits to both health centers increased by 85%. Three-quarters of increased time was spent waiting. Despite nearly doubling visits, there was no change in clinical officers' work patterns, but the nurses' and the clerks' patient care time decreased after EMR implementation. Providers were generally satisfied with the EMR but desired additional training. Conclusions: We successfully implemented a primary care EMR in three rural Kenyan health centers. Patient waiting time was dramatically lengthened while the nurses' and the clerks' patient care time decreased. Long-term use of EMRs in such settings will require changes in culture and workflow.Item Assessment of Discordance Between Surrogate Care Goals and Medical Treatment Provided to Older Adults With Serious Illness(JAMA Network, 2020-05) Comer, Amber R.; Hickman, Susan E.; Slaven, James E.; Monahan, Patrick O.; Sachs, Greg A.; Wocial, Lucia D.; Burke, Emily S.; Torke, Alexia M.; Health Sciences, School of Health and Human SciencesImportance: An important aspect of high-quality care is ensuring that treatments are in alignment with patient or surrogate decision-maker goals. Treatment discordant with patient goals has been shown to increase medical costs and prolong end-of-life difficulties. Objectives: To evaluate discordance between surrogate decision-maker goals of care and medical orders and treatments provided to hospitalized, incapacitated older patients. Design, setting, and participants: This prospective cohort study included 363 patient-surrogate dyads. Patients were 65 years or older and faced at least 1 major medical decision in the medical and medical intensive care unit services in 3 tertiary care hospitals in an urban Midwestern area. Data were collected from April 27, 2012, through July 10, 2015, and analyzed from October 5, 2018, to December 5, 2019. Main outcomes and measures: Each surrogate's preferred goal of care was determined via interview during initial hospitalization and 6 to 8 weeks after discharge. Surrogates were asked to select the goal of care for the patient from 3 options: comfort-focused care, life-sustaining treatment, or an intermediate option. To assess discordance, the preferred goal of care as determined by the surrogate was compared with data from medical record review outlining the medical treatment received during the target hospitalization. Results: A total of 363 dyads consisting of patients (223 women [61.4%]; mean [SD] age, 81.8 [8.3] years) and their surrogates (257 women [70.8%]; mean [SD] age, 58.3 [11.2] years) were included in the analysis. One hundred sixty-nine patients (46.6%) received at least 1 medical treatment discordant from their surrogate's identified goals of care. The most common type of discordance involved full-code orders for patients with a goal of comfort (n = 41) or an intermediate option (n = 93). More frequent in-person contact between surrogate and patient (adjusted odds ratio [AOR], 0.43; 95% CI, 0.23-0.82), patient residence in an institution (AOR, 0.44; 95% CI, 0.23-0.82), and surrogate-rated quality of communication (AOR, 0.98; 95% CI, 0.96-0.99) were associated with lower discordance. Surrogate marital status (AOR for single vs married, 1.92; 95% CI, 1.01-3.66), number of family members involved in decisions (AOR for ≥2 vs 0-1, 1.84; 95% CI, 1.05-3.21), and religious affiliation (AOR for none vs any, 4.87; 95% CI, 1.12-21.09) were associated with higher discordance. Conclusions and relevance: This study found that discordance between surrogate goals of care and medical treatments for hospitalized, incapacitated patients was common. Communication quality is a modifiable factor associated with discordance that may be an avenue for future interventions.Item The Association of Surrogate Decision Makers’ Religious and Spiritual Beliefs with End of Life Decisions(Elsevier, 2020-02) Torke, Alexia M.; Fitchett, George; Maiko, Saneta; Burke, Emily S.; Slaven, James E.; Newton Watson, Beth; Ivy, Steven; Monahan, Patrick O.; Biostatistics, School of Public HealthContext: Although religion and spirituality are important to surrogate decision makers, little is known about the role of religion in decision making regarding life-sustaining treatments. Objectives: To determine the relationships between dimensions of religion and spirituality and medical treatment decisions made by surrogates. Methods: This prospective observational study enrolled patient/surrogate dyads from three hospitals in one metropolitan area. Eligible patients were 65 years or older and admitted to the medicine or medical intensive care services. Baseline surveys between hospital days 2 and 10 assessed seven dimensions of religion and spirituality. Chart reviews of the electronic medical record and regional health information exchange six months after enrollment identified the use of life-sustaining treatments and hospice for patients who died. Results: There were 291 patient/surrogate dyads. When adjusting for other religious dimensions, demographic, and illness factors, only surrogates' belief in miracles was significantly associated with a lower surrogate preference for do-not-resuscitate status (adjusted odds ratio [aOR] 0.39; 95% CI 0.19, 0.78). Among patients who died, higher surrogate intrinsic religiosity was associated with lower patient receipt of life-sustaining treatments within the last 30 days (aOR 0.66; 95% CI 0.45, 0.97). Belief in miracles (aOR 0.30; 95% CI 0.10, 0.96) and higher intrinsic religiosity (aOR 0.70; 95% CI 0.53, 0.93) were associated with lower hospice utilization. Conclusion: Few religious variables are associated with end-of-life preferences or treatment. Belief in miracles and intrinsic religiosity may affect treatment and should be identified and explored with surrogates by trained chaplains or other clinicians with appropriate training.Item Associations of objectively measured and self-reported sleep duration with carotid artery intima media thickness among police officers(Wiley, 2013-11) Ma, Claudia C.; Burchfiel, Cecil M.; Charles, Luenda E.; Dorn, Joan M.; Andrew, Michael E.; Kook Gu, Ja; Joseph, Parveen Nedra; Fekedulegn, Desta; Slaven, James E.; Hartley, Tara A.; Mnatsakanova, Anna; Violanti, John M.; Biostatistics, School of MedicineBACKGROUND: We aimed to examine the association of objectively measured and self-reported sleep duration with carotid artery intima media thickness (IMT) among 257 police officers, a group at high risk for cardiovascular disease (CVD). METHODS: Sleep duration was estimated using actigraphic data and through self-reports. The mean maximum IMT was the average of the largest 12 values scanned bilaterally from three angles of the near and far wall of the common carotid, bulb, and internal carotid artery. Linear and quadratic regression models were used to assess the association of sleep duration with IMT. RESULTS: Officers who had fewer than 5 or 8 hr or more of objectively measured sleep duration had significantly higher maximum IMT values, independent of age. Self-reported sleep duration was not associated with either IMT measure. CONCLUSION: Attainment of sufficient sleep duration may be considered as a possible strategy for atherosclerosis prevention among police officers.Item Caspofungin Increases Fungal Chitin and Eosinophil and γδ T Cell-Dependent Pathology in Invasive Aspergillosis(American Association of Immunologists, 2017-07-15) Amarsaikhan, Nansalmaa; Sands, Ethan M.; Shah, Anand; Abdolrasouli, Ali; Reed, Anna; Slaven, James E.; Armstrong-James, Darius; Templeton, Steven P.; Microbiology and Immunology, School of MedicineThe polysaccharide-rich fungal cell wall provides pathogen-specific targets for antifungal therapy and distinct molecular patterns that stimulate protective or detrimental host immunity. The echinocandin antifungal caspofungin inhibits synthesis of cell wall β-1,3-glucan and is used for prophylactic therapy in immune-suppressed individuals. However, breakthrough infections with fungal pathogen Aspergillus fumigatus are associated with caspofungin prophylaxis. In this study, we report in vitro and in vivo increases in fungal surface chitin in A. fumigatus induced by caspofungin that was associated with airway eosinophil recruitment in neutropenic mice with invasive pulmonary aspergillosis (IA). More importantly, caspofungin treatment of mice with IA resulted in a pattern of increased fungal burden and severity of disease that was reversed in eosinophil-deficient mice. Additionally, the eosinophil granule proteins major basic protein and eosinophil peroxidase were more frequently detected in the bronchoalveolar lavage fluid of lung transplant patients diagnosed with IA that received caspofungin therapy when compared with azole-treated patients. Eosinophil recruitment and inhibition of fungal clearance in caspofungin-treated mice with IA required RAG1 expression and γδ T cells. These results identify an eosinophil-mediated mechanism for paradoxical caspofungin activity and support the future investigation of the potential of eosinophil or fungal chitin-targeted inhibition in the treatment of IA.Item Characterization of Spontaneous and Induced Puberty in Girls with Turner Syndrome(American Association of Clinical Endocrinologists, 2017-07) Folsom, Lisal J.; Slaven, James E.; Nabhan, Zeina M.; Eugster, Erica A.; Medicine, School of MedicineOBJECTIVE: To characterize puberty in girls with Turner syndrome (TS) and determine whether specific patient characteristics are associated with the timing of menarche. We also sought to compare spontaneous versus induced puberty in these patients. METHODS: Medical records of girls followed in our Pediatric Endocrine clinic for TS from 2007 to 2015 were reviewed. RESULTS: Fifty-three girls were included, of whom 10 (19%) achieved menarche spontaneously and 43 (81%) received hormone replacement therapy (HRT). Of girls receiving HRT, a younger age at estrogen initiation correlated with a longer time to menarche (P = .02), and a mosaic karyotype was associated with a shorter time to menarche (P = .02), whereas no relationship was seen for body mass index, estrogen regimen, or maternal age at menarche. Nineteen girls (44%) receiving HRT had bleeding on estrogen alone at a wide dose range and were more likely to be on transdermal than oral preparations (P = .01). Girls with spontaneous puberty achieved menarche at a younger age (P<.01) and were more likely to have mosaic TS (P = .02). CONCLUSION: Significant variability in the timing of menarche exists among girls with TS. However, age at pubertal induction and karyotype were significantly correlated with age at menarche in our patients. A wide range of estrogen doses is seen in girls who bleed prior to progesterone, suggesting extreme variability in estrogen sensitivity among patients with TS. Girls achieving spontaneous menarche are younger and more likely to have a mosaic karyotype than those with induced menarche. Large-scale prospective studies are needed to confirm these results.Item The Complex Relationship between Pain Intensity and Physical Functioning in Fibromyalgia: The Mediating Role of Depression(Journal of Applied Biobehavioral Research, 2017) Steiner, Jennifer L.; Bigatti, Silvia M.; Slaven, James E.; Ang, Dennis C.Fibromyalgia (FM) is typically associated with the experience of diffuse pain and physical impairment.Depression also commonly co-exists in patients with FM, and has been correlated with pain intensity and physical functioning.Previous research suggests an association between pain intensity and physical functioning; however, the direct causal relationship between improvements in pain intensity and in functioning is not observed in many FM patients.This may suggest that another factor such as depression is mediating this relationship. The present work examinedmediating role of depression. METHODS: 216 patients with FM completed measures of pain intensity, depression, and physical functionas part of a larger longitudinal study.Assessments were completed at baseline, 12, 24, and 36 weeks.RESULTS: Longitudinal mediational analyses indicated that depression is a partial mediator of the relationship between pain intensity and physical functioningat all four assessment points.Beta coefficients for the path from pain to physical functioning ranged from 0.18 –0.36, with attenuated path coefficients ranging from 0.03 –0.08, still showing significant but decreased associations when depression was added as a mediator. CONCLUSIONS: Clinical implication includes the importance of treating co-morbid depression in patients with fibromyalgia early in the course of treatment to prevent engagement in the cycle of disability.