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Item Are Pain Management Questions in Patient Satisfaction Surveys Driving the Opioid Epidemic?(American Public Health Association, 2016-06) Adams, Jerome; Bledsoe, Gregory H.; Armstrong, John H.; Anesthesia, School of MedicineItem Assessment of the Protocol-Guided Rapid Evaluation of Veterans Experiencing New Transient Neurological Symptoms (PREVENT) Program for Improving Quality of Care for Transient Ischemic Attack: A Nonrandomized Cluster Trial(American Medical Association, 2020-09-08) Bravata, Dawn M.; Myers, Laura J.; Perkins, Anthony J.; Zhang, Ying; Miech, Edward J.; Rattray, Nicholas A.; Penney, Lauren S.; Levine, Deborah; Sico, Jason J.; Cheng, Eric M.; Damush, Teresa M.; Medicine, School of MedicineImportance Patients with transient ischemic attack (TIA) are at high risk of recurrent vascular events. Timely management can reduce that risk by 70%; however, gaps in TIA quality of care exist. Objective To assess the performance of the Protocol-Guided Rapid Evaluation of Veterans Experiencing New Transient Neurological Symptoms (PREVENT) intervention to improve TIA quality of care. Design, Setting, and Participants This nonrandomized cluster trial with matched controls evaluated a multicomponent intervention to improve TIA quality of care at 6 diverse medical centers in 6 geographically diverse states in the US and assessed change over time in quality of care among 36 matched control sites (6 control sites matched to each PREVENT site on TIA patient volume, facility complexity, and quality of care). The study period (defined as the data period) started on August 21, 2015, and extended to May 12, 2019, including 1-year baseline and active implementation periods for each site. The intervention targeted clinical teams caring for patients with TIA. Intervention The quality improvement (QI) intervention included the following 5 components: clinical programs, data feedback, professional education, electronic health record tools, and QI support. Main Outcomes and Measures The primary outcome was the without-fail rate, which was calculated as the proportion of veterans with TIA at a specific facility who received all 7 guideline-recommended processes of care for which they were eligible (ie, anticoagulation for atrial fibrillation, antithrombotic use, brain imaging, carotid artery imaging, high- or moderate-potency statin therapy, hypertension control, and neurological consultation). Generalized mixed-effects models with multilevel hierarchical random effects were constructed to evaluate the intervention associations with the change in the mean without-fail rate from the 1-year baseline period to the 1-year intervention period. Results Six facilities implemented the PREVENT QI intervention, and 36 facilities were identified as matched control sites. The mean (SD) age of patients at baseline was 69.85 (11.19) years at PREVENT sites and 71.66 (11.29) years at matched control sites. Most patients were male (95.1% [154 of 162] at PREVENT sites and 94.6% [920 of 973] at matched control sites at baseline). Among the PREVENT sites, the mean without-fail rate improved substantially from 36.7% (58 of 158 patients) at baseline to 54.0% (95 of 176 patients) during a 1-year implementation period (adjusted odds ratio, 2.10; 95% CI, 1.27-3.48; P = .004). Comparing the change in quality at the PREVENT sites with the matched control sites, the improvement in the mean without-fail rate was greater at the PREVENT sites than at the matched control sites (36.7% [58 of 158 patients] to 54.0% [95 of 176 patients] [17.3% absolute improvement] vs 38.6% [345 of 893 patients] to 41.8% [363 of 869 patients] [3.2% absolute improvement], respectively; absolute difference, 14%; P = .008). Conclusions and Relevance The implementation of this multifaceted program was associated with improved TIA quality of care across the participating sites. The PREVENT QI program is an example of a health care system using QI strategies to improve performance, and may serve as a model for other health systems seeking to provide better care. Trial Registration ClinicalTrials.gov Identifier: NCT02769338 Go to: Introduction Approximately 8500 veterans with transient ischemic attack (TIA) or ischemic stroke are cared for in Department of Veterans Affairs (VA) emergency departments (EDs) or inpatient wards annually in the United States.1 Patients with TIA generally present with transient neurological symptoms of a presumed ischemic cause.2 Patients with TIA are at a high risk of recurrent vascular events3,4,5; however, delivery of timely TIA care can reduce that risk by up to 70%.6,7,8,9 Despite the known benefits of timely TIA care, gaps in TIA quality of care exist in both private-sector US hospitals10 and VA facilities.11,12 In a learning health care system, “clinical informatics, incentives, and culture are aligned to promote continuous improvement and innovation, with best practices seamlessly embedded in the delivery process and new knowledge captured as an integral by-product of the delivery experience.”13(p136) Within a learning health care system, health care teams respond to quality problems by using quality improvement (QI) strategies and systems redesign approaches to improve performance, depending on the complexity and scope of the problem.14 The objective of the Protocol-Guided Rapid Evaluation of Veterans Experiencing New Transient Neurological Symptoms (PREVENT) trial was to evaluate a multicomponent QI intervention to improve the quality of TIA care.15 The PREVENT intervention was designed to align with the learning health care system model.13,15Item 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 HealthINTRODUCTION: 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.Item Bone mineral density reductions after tenofovir disoproxil fumarate initiation and changes in phosphaturia: a secondary analysis of ACTG A5224s(Oxford Academic, 2017-07-01) Gupta, Samir K.; Yeh, Eunice; Kitch, Douglas W.; Brown, Todd T.; Venuto, Charles S.; Morse, Gene D.; Ha, Belinda; Melbourne, Kathleen; McComsey, Grace A.; Medicine, School of MedicineBackground: It is unknown if the greater reductions in bone mineral density (BMD) associated with initiation of tenofovir disoproxil fumarate compared with abacavir in previously untreated HIV-infected participants in the ACTG A5224s clinical trial were associated with potentially worsening tenofovir-related phosphaturia. Methods: We correlated changes in BMD at the hip and spine with changes in phosphaturia [transtubular reabsorption of phosphorus (TRP) and tubular maximum phosphate reabsorption per glomerular filtration rate (TmP/GFR)] from entry through week 96 in those initiating tenofovir ( n = 134) versus abacavir ( n = 135) with efavirenz or atazanavir/ritonavir in A5224s. We also correlated changes in BMD with tenofovir AUC measured between weeks 4 and 24. Results: Changes in TRP and TmP/GFR through week 96 between the tenofovir and abacavir arms were not significantly different (both P ≥ 0.70) and did not differ with use of efavirenz versus atazanavir/ritonavir. There were no significant correlations between changes in either TRP or TmP/GFR and with either hip or spine BMD in the tenofovir arms. Tenofovir AUC was significantly correlated with changes in hip BMD, but not spine BMD, at week 24 ( r = -0.22, P = 0.028) and week 48 ( r = -0.26, P = 0.010), but not at week 96 ( r = -0.14, P = 0.18). Conclusions: Changes in phosphaturia were not different between the tenofovir and abacavir arms in A5224s. Changes in hip and spine BMD with tenofovir were not related to changes in phosphaturia. However, tenofovir exposure was weakly associated with changes in hip BMD through week 48.Item C-reactive protein and risk of cognitive decline: The REGARDS study(PLOS, 2020-12-31) Rentería, Miguel Arce; Gillett, Sarah R.; McClure, Leslie A.; Wadley, Virginia G.; Glasser, Stephen P.; Howard, Virginia J.; Kissela, Brett M.; Unverzagt, Frederick W.; Jenny, Nancy S.; Manly, Jennifer J.; Cushman, Mary; Psychiatry, School of MedicineMarkers of systemic inflammation are associated with increased risk of cognitive impairment, but it is unclear if they are associated with a faster rate of cognitive decline and whether this relationship differs by race. Our objective was to examine the association of baseline C-reaction protein (CRP) with cognitive decline among a large racially diverse cohort of older adults. Participants included 21,782 adults aged 45 and older (36% were Black, Mean age at baseline 64) from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. CRP was measured at baseline and used as a continuous variable or a dichotomous grouping based on race-specific 90th percentile cutoffs. Cognitive measures of memory and verbal fluency were administered every 2 years for up to 12 years. Latent growth curve models evaluated the association of CRP on cognitive trajectories, adjusting for relevant demographic and health factors. We found that higher CRP was associated with worse memory (B = -.039, 95% CI [-.065,-.014]) and verbal fluency at baseline (B = -.195, 95% CI [-.219,-.170]), but not with rate of cognitive decline. After covariate adjustment, the association of CRP on memory was attenuated (B = -.005, 95% CI [-.031,-.021]). The association with verbal fluency at baseline, but not over time, remained (B = -.042, 95% CI [-.067,-.017]). Race did not modify the association between CRP and cognition. Findings suggest that levels of CRP at age 45+, are a marker of cognitive impairment but may not be suitable for risk prediction for cognitive decline.Item Identification of TMEM230 mutations in familial Parkinson's disease(Nature Research, 2016-07) Deng, Han-Xiang; Shi, Yong; Yang, Yi; Ahmeti, Kreshnik B.; Miller, Nimrod; Huang, Cao; Cheng, Lijun; Zhai, Hong; Deng, Sheng; Nuytemans, Karen; Corbett, Nicola J.; Kim, Myung Jong; Deng, Hao; Tang, Baisha; Yang, Ziquang; Xu, Yanming; Chen, Piao; Huang, Bo; Gao, Xiao-Ping; Song, Zhi; Liu, Zhenhua; Fecto, Faisal; Siddique, Nailah; Foroud, Tatiana; Jankovic, Joseph; Ghetti, Bernardino; Nicholson, Daniel A.; Krainc, Dimitri; Melen, Onur; Vance, Jeffery M.; Pericak-Vance, Margaret A.; Ma, Yong-Chao; Rajput, Ali H.; Siddique, Teepu; Medical and Molecular Genetics, School of MedicineParkinson's disease is the second most common neurodegenerative disorder without effective treatment. It is generally sporadic with unknown etiology. However, genetic studies of rare familial forms have led to the identification of mutations in several genes, which are linked to typical Parkinson's disease or parkinsonian disorders. The pathogenesis of Parkinson's disease remains largely elusive. Here we report a locus for autosomal dominant, clinically typical and Lewy body-confirmed Parkinson's disease on the short arm of chromosome 20 (20pter-p12) and identify TMEM230 as the disease-causing gene. We show that TMEM230 encodes a transmembrane protein of secretory/recycling vesicles, including synaptic vesicles in neurons. Disease-linked TMEM230 mutants impair synaptic vesicle trafficking. Our data provide genetic evidence that a mutant transmembrane protein of synaptic vesicles in neurons is etiologically linked to Parkinson's disease, with implications for understanding the pathogenic mechanism of Parkinson's disease and for developing rational therapies.Item Is Low Health Literacy Associated with Increased Emergency Department Utilization and Recidivism?(Wiley Online Library, 2014-10) Griffey, Richard T.; Kennedy, Sarah K.; McGownan, Lucy; Kaphingst, Kimberly A.; Department of Emergency Medicine, IU School of MedicineOBJECTIVES: The objective was to determine whether patients with low health literacy have higher emergency department (ED) utilization and higher ED recidivism than patients with adequate health literacy. METHODS: The study was conducted at an urban academic ED with more than 95,000 annual visits that is part of a 13-hospital health system, using electronic records that are captured in a central data repository. As part of a larger, cross-sectional, convenience sample study, health literacy testing was performed using the short test of functional health literacy in adults (S-TOFHLA) and standard test thresholds identifying those with inadequate, marginal, and adequate health literacy. The authors collected patients' demographic and clinical data, including items known to affect recidivism. This was a structured electronic record review directed at determining 1) the median number of total ED visits in this health system within a 2-year period and 2) the proportion of patients with each level of health literacy who had return visits within 3, 7, and 14 days of index visits. Descriptive data for demographics and ED returns are reported, stratified by health literacy level. The Mantel-Haenszel chi-square was used to test whether there is an association between health literacy and ED recidivism. A negative binomial multivariable model was performed to examine whether health literacy affects ED use, including variables significant at the 0.1 alpha level on bivariate analysis and retaining those significant at an alpha of 0.05 in the final model. RESULTS: Among 431 patients evaluated, 13.2% had inadequate, 10% had marginal, and 76.3% had adequate health literacy as identified by S-TOFHLA. Patients with inadequate health literacy had higher ED utilization compared to those with adequate health literacy (p = 0.03). Variables retained in the final model included S-TOFHLA score, number of medications, having a personal doctor, being a property owner, race, insurance, age, and simple comorbidity score. During the study period, 118 unique patients each made at least one return ED visit within a 14-day period. The proportion of patients with inadequate health literacy making at least one return visit was higher than that of patients with adequate health literacy at 14 days, but was not significantly higher within 3 or 7 days. CONCLUSIONS: In this single-center study, higher utilization of the ED by patients with inadequate health literacy when compared to those with adequate health literacy was observed. Patients with inadequate health literacy made a higher number of return visits at 14 days but not at 3 or 7 days.Item Menopause and Big Data: Word Adjacency Graph Modeling of Menopause-Related ChaCha® Data(Wolters Kluwer, 2017-07) Carpenter, Janet S.; Groves, Doyle; Chen, Chen X.; Otte, Julie L.; Miller, Wendy; School of NursingOBJECTIVE: To detect and visualize salient queries about menopause using Big Data from ChaCha. METHODS: We used Word Adjacency Graph (WAG) modeling to detect clusters and visualize the range of menopause-related topics and their mutual proximity. The subset of relevant queries was fully modeled. We split each query into token words (ie, meaningful words and phrases) and removed stopwords (ie, not meaningful functional words). The remaining words were considered in sequence to build summary tables of words and two and three-word phrases. Phrases occurring at least 10 times were used to build a network graph model that was iteratively refined by observing and removing clusters of unrelated content. RESULTS: We identified two menopause-related subsets of queries by searching for questions containing menopause and menopause-related terms (eg, climacteric, hot flashes, night sweats, hormone replacement). The first contained 263,363 queries from individuals aged 13 and older and the second contained 5,892 queries from women aged 40 to 62 years. In the first set, we identified 12 topic clusters: 6 relevant to menopause and 6 less relevant. In the second set, we identified 15 topic clusters: 11 relevant to menopause and 4 less relevant. Queries about hormones were pervasive within both WAG models. Many of the queries reflected low literacy levels and/or feelings of embarrassment. CONCLUSIONS: We modeled menopause-related queries posed by ChaCha users between 2009 and 2012. ChaCha data may be used on its own or in combination with other Big Data sources to identify patient-driven educational needs and create patient-centered interventions.Item The Minimal Clinically Important Difference for the Mayo-Portland Adaptability Inventory(Wolters Kluwer, 2017-07) Malec, James F.; Kean, Jacob; Monahan, Patrick O.; Physical Medicine and Rehabilitation, School of MedicineOBJECTIVES: To determine the Minimal Clinically Important Difference (MCID) and Robust Clinically Important Difference (RCID) of the Mayo-Portland Adaptability Inventory-4 (MPAI-4) as measures of response to intervention. METHODS: Retrospective analysis of existing data. Both distribution- and anchor-based methods were used to triangulate on the MCID and to identify a moderate, that is, more robust, level of change (RCID) for the MPAI-4. These were further evaluated with respect to clinical provider ratings. PARTICIPANTS: Data for individuals with acquired brain injury in rehabilitation programs throughout the United States in the OutcomeInfo Database (n = 3087) with 2 MPAI-4 ratings. MAIN MEASURES: MPAI-4, Supervision Rating Scale, Clinician Rating of Global Clinical Improvement. RESULTS: Initial analyses suggested 5 T-score points (5T) as the MCID and 9T as the RCID. Eighty-one percent to 87% of clinical raters considered a 5T change and 99% considered a 9T change to indicate meaningful improvement. CONCLUSIONS: 5T represents the MCID for the MPAI-4 and 9T, the RCID. Both values are notably less than the Reliable Change Index (RCI). While the RCI indicates change with a high level of statistical confidence, it may be insensitive to change that is considered meaningful by providers and participants as indicated by the MCID.Item A (p)ppGpp-Null Mutant of Haemophilus ducreyi Is Partially Attenuated in Humans Due to Multiple Conflicting Phenotypes(American Society for Microbiology (ASM), 2014-08) Holley, Concerta; Gangaiah, Dharanesh; Li, Wei; Fortney, Kate R.; Janowicz, Diane M.; Ellinger, Sheila; Zwickl, Beth; Katz, Barry P.; Spinola, Stanley M.; Department of Microbiology & Immunology, IU School of Medicine(p)ppGpp responds to nutrient limitation through a global change in gene regulation patterns to increase survival. The stringent response has been implicated in the virulence of several pathogenic bacterial species. Haemophilus ducreyi, the causative agent of chancroid, has homologs of both relA and spoT, which primarily synthesize and hydrolyze (p)ppGpp in Escherichia coli. We constructed relA and relA spoT deletion mutants to assess the contribution of (p)ppGpp to H. ducreyi pathogenesis. Both the relA single mutant and the relA spoT double mutant failed to synthesize (p)ppGpp, suggesting that relA is the primary synthetase of (p)ppGpp in H. ducreyi. Compared to the parent strain, the double mutant was partially attenuated for pustule formation in human volunteers. The double mutant had several phenotypes that favored attenuation, including increased sensitivity to oxidative stress. The increased sensitivity to oxidative stress could be complemented in trans. However, the double mutant also exhibited phenotypes that favored virulence. When grown to the mid-log phase, the double mutant was significantly more resistant than its parent to being taken up by human macrophages and exhibited increased transcription of lspB, which is involved in resistance to phagocytosis. Additionally, compared to the parent, the double mutant also exhibited prolonged survival in the stationary phase. In E. coli, overexpression of DksA compensates for the loss of (p)ppGpp; the H. ducreyi double mutant expressed higher transcript levels of dksA than the parent strain. These data suggest that the partial attenuation of the double mutant is likely the net result of multiple conflicting phenotypes.