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Item Adaptation of the Client Diagnostic Questionnaire for East Africa(Public Library of Science, 2024-03-19) Kwobah, Edith Kamaru; Goodrich, Suzanne; Kulzer, Jayne Lewis; Kanyesigye, Michael; Obatsa, Sarah; Cheruiyot, Julius; Kiprono, Lorna; Kibet, Colma; Ochieng, Felix; Bukusi, Elizabeth A.; Ofner, Susan; Brown, Steven A.; Yiannoutsos, Constantin T.; Atwoli, Lukoye; Wools-Kaloustian, Kara; Medicine, School of MedicineResearch increasingly involves cross-cultural work with non-English-speaking populations, necessitating translation and cultural validation of research tools. This paper describes the process of translating and criterion validation of the Client Diagnostic Questionnaire (CDQ) for use in a multisite study in Kenya and Uganda. The English CDQ was translated into Swahili, Dholuo (Kenya) and Runyankole/Rukiga (Uganda) by expert translators. The translated documents underwent face validation by a bilingual committee, who resolved unclear statements, agreed on final translations and reviewed back translations to English. A diagnostic interview by a mental health specialist was used for criterion validation, and Kappa statistics assessed the strength of agreement between non-specialist scores and mental health professionals' diagnoses. Achieving semantic equivalence between translations was a challenge. Validation analysis was done with 30 participants at each site (median age 32.3 years (IQR = (26.5, 36.3)); 58 (64.4%) female). The sensitivity was 86.7%, specificity 64.4%, positive predictive value 70.9% and negative predictive value 82.9%. Diagnostic accuracy by the non-specialist was 75.6%. Agreement was substantial for major depressive episode and positive alcohol (past 6 months) and alcohol abuse (past 30 days). Agreement was moderate for other depressive disorders, panic disorder and psychosis screen; fair for generalized anxiety, drug abuse (past 6 months) and Post Traumatic Stress Disorder (PTSD); and poor for drug abuse (past 30 days). Variability of agreement between sites was seen for drug use (past 6 months) and PTSD. Our study successfully adapted the CDQ for use among people living with HIV in East Africa. We established that trained non-specialists can use the CDQ to screen for common mental health and substance use disorders with reasonable accuracy. Its use has the potential to increase case identification, improve linkage to mental healthcare, and improve outcomes. We recommend further studies to establish the psychometric properties of the translated tool.Item Bleeding Risk, Physical Functioning, and Non-use of Anticoagulation Among Patients with Stroke and Atrial Fibrillation(2014-08) Schmid, Arlene A.; Ofner, Susan; Shorr, Ronald I; Williams, Linda S.; Bravata, Dawn M.Background: Atrial fibrillation (AF) is common among people with stroke. Anticoagulation medications can be used to manage the deleterious impact of AF after stroke, however may not be prescribed due to concerns about post-stroke falls and decreased functioning. Thus, the purpose of this study was to identify, among people with stroke and AF, predictors of anticoagulation prescription at hospital discharge. Methods: This is a secondary analysis of a retrospective cohort study of data retrieved via medical records, including: National Institutes of Health Stroke Scale score; Functional Independence Measure (FIM) motor score (motor or physical function); ambulation on 2nd day of hospitalization; Morse Falls Scale (fall risk); and HAS-BLED score (Hypertension; Abnormal renal and liver function; Stroke; Bleeding; Labile INRs; Elderly > 65; and Drugs or alcohol). Data analyses included bivariate comparisons between people with and without anticoagulation at discharge. Logistic-regression modeling was used to assess predictors of discharge anti-coagulation. Results: There were 334 subjects included in the analyses, average age was 75 years old. Anticoagulation was prescribed at discharge for 235 (70%) of patients. In the adjusted regression analyses, only the FIM motor score (adjusted OR = 1.015, 95%CI 1.001-1.028) and the HAS-BLED score (adjusted OR = 0.36, 95%CI 0.22-0.58) were significantly associated with anticoagulation prescription at discharge. Conclusion: It appears that in this sample, post-stroke anti-coagulation decisions appear to be made based on clinical factors associated with bleed risk and motor deficits or physical functioning. However, opportunities may exist for improving clinician documentation of specific reasoning for non-anticoagulation prescription.Item Cardiac Troponin I-interacting Kinase impacts cardiomyocyte S-phase activity but not cardiomyocyte proliferation(American Heart Association, 2023) Reuter, Sean P.; Soonpaa, Mark H.; Field, Dorothy; Simpson, Ed; Rubart-von der Lohe, Michael; Lee, Han Kyu; Sridhar, Arthi; Ware, Stephanie M.; Green, Nick; Li, Xiaochun; Ofner, Susan; Marchuk, Douglas A.; Wollert, Kai C.; Field, Loren J.; Pediatrics, School of MedicineBackground: Identifying genetic variants that affect the level of cell cycle reentry and establishing the degree of cell cycle progression in those variants could help guide development of therapeutic interventions aimed at effecting cardiac regeneration. We observed that C57Bl6/NCR (B6N) mice have a marked increase in cardiomyocyte S-phase activity after permanent coronary artery ligation compared with infarcted DBA/2J (D2J) mice. Methods: Cardiomyocyte cell cycle activity after infarction was monitored in D2J, (D2J×B6N)-F1, and (D2J×B6N)-F1×D2J backcross mice by means of bromodeoxyuridine or 5-ethynyl-2'-deoxyuridine incorporation using a nuclear-localized transgenic reporter to identify cardiomyocyte nuclei. Genome-wide quantitative trait locus analysis, fine scale genetic mapping, whole exome sequencing, and RNA sequencing analyses of the backcross mice were performed to identify the gene responsible for the elevated cardiomyocyte S-phase phenotype. Results: (D2J×B6N)-F1 mice exhibited a 14-fold increase in cardiomyocyte S-phase activity in ventricular regions remote from infarct scar compared with D2J mice (0.798±0.09% versus 0.056±0.004%; P<0.001). Quantitative trait locus analysis of (D2J×B6N)-F1×D2J backcross mice revealed that the gene responsible for differential S-phase activity was located on the distal arm of chromosome 3 (logarithm of the odds score=6.38; P<0.001). Additional genetic and molecular analyses identified 3 potential candidates. Of these, Tnni3k (troponin I-interacting kinase) is expressed in B6N hearts but not in D2J hearts. Transgenic expression of TNNI3K in a D2J genetic background results in elevated cardiomyocyte S-phase activity after injury. Cardiomyocyte S-phase activity in both Tnni3k-expressing and Tnni3k-nonexpressing mice results in the formation of polyploid nuclei. Conclusions: These data indicate that Tnni3k expression increases the level of cardiomyocyte S-phase activity after injury.Item Care Trajectories of Veterans in the Twelve Months following Hospitalization for Acute Ischemic Stroke(AHA, 2015-10) Arling, Greg; Ofner, Susan; Reeves, Mathew J.; Myers, Laura J.; Williams, Linda S.; Daggy, Joanne K.; Phipps, Michael S.; Chumbler, Neale R.; Bravata, Dawn M.; Department of Neurology, IU School of MedicineBackground—Recovery after a stroke varies greatly between individuals and is reflected by wide variation in the use of institutional and home care services. This study sought to classify veterans according to their care trajectories in the 12 months after hospitalization for ischemic stroke. Methods and Results—The sample consisted of 3811 veterans hospitalized for ischemic stroke in Veterans Health Administration facilities in 2007. Three outcomes—nursing home care, home care, and mortality—were modeled jointly >12 months using latent class growth analysis. Data on Veterans’ care use and cost came from the Veterans Administration and Medicare. Covariates included stroke severity (National Institutes of Health Stroke Scale), functional status (functional independence measure score), age, marital status, chronic conditions, and prestroke ambulation. Five care trajectories were identified: 49% of Veterans had Rapid Recovery with little or no use of care; 15% had a Steady Recovery with initially high nursing home or home care that tapered off; 9% had Long-Term Home Care; 13% had Long-Term Nursing Home Care; and 14% had an Unstable trajectory with multiple transitions between long-term and acute care settings. Care use was greatest for individuals with more severe strokes, lower functioning at hospital discharge, and older age. Average annual costs were highest for individuals with the Long-Term Nursing Home trajectory ($63 082), closely followed by individuals with the Unstable trajectory ($58 720). Individual with the Rapid Recovery trajectory had the lowest costs ($9271). Conclusions—Care trajectories after stroke were associated with stroke severity and functional dependency and they had a dramatic impact on subsequent costs.Item Comparison of Risk of Recrudescent Fever in Children With Kawasaki Disease Treated With Intravenous Immunoglobulin and Low-Dose vs High-Dose Aspirin(JAMA Network, 2020-01-03) Platt, Brooks; Belarski, Emily; Manaloor, John; Ofner, Susan; Carroll, Aaron E.; John, Chandy C.; Wood, James B.; Medicine, School of MedicineImportance: Timely initiation of intravenous immunoglobulin plus aspirin is necessary for decreasing the risk of recrudescent fever and coronary artery abnormalities in children with Kawasaki disease (KD). The optimal dose of aspirin, however, remains unclear. Objective: To evaluate whether initial treatment with low-dose compared with high-dose aspirin in children with KD is associated with an increase in fever recrudescence. Design, Setting, and Participants: A retrospective cohort study of 260 children with KD at Riley Hospital for Children, Indianapolis, Indiana, between January 1, 2007, and December 31, 2018, was conducted. Children aged 0 to 18 years with a first episode of KD, identified by International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis codes treated within 10 days of symptom onset with high-dose intravenous immunoglobulin plus aspirin were eligible. Patients who received an alternative diagnosis, experienced a second episode of KD, did not receive intravenous immunoglobulin plus aspirin for initial treatment, were not treated within 10 days of symptoms, or had incomplete records were excluded. Exposures: High-dose (≥10 mg/kg/d) or low-dose (<10 mg/kg/d) aspirin therapy. Main Outcomes and Measures: The primary outcome was recrudescent fever necessitating retreatment of KD. The secondary outcomes were coronary artery abnormalities and hospital length of stay. Results: Among the 260 patients included, the median (interquartile range) age was 2.5 (1.6-4.3) years, 103 (39.6%) were girls, 166 (63.8%) were non-Hispanic white, 57 (21.9%) were African American, 22 (8.5%) were Asian, 11 (4.2%) were Hispanic, and 4 (1.5%) were of unknown race/ethnicity. One hundred-forty-two patients (54.6%) were treated with low-dose aspirin. There was no association between recrudescent fever and aspirin dose, with 39 children (27.5%) having recrudescent fever in the low-dose group compared with 26 children (22.0%) in the high-dose group (odds ratio [OR], 1.34; 95% CI, 0.76-2.37; P = .31), with similar results after adjusting for potential confounding variables (OR, 1.63; 95% CI, 0.89-2.97; P = .11). In a subset analysis of 167 children with complete KD, however, there was nearly a 2-fold difference in the odds of recrudescent fever with low-dose aspirin (OR, 1.87; 95% CI, 0.82-4.23; P = .14), although this difference did not reach statistical significance. In addition, no association was identified between treatment group and coronary artery abnormalities (low-dose, 7.4% vs high-dose, 9.4%; OR, 0.86; 95% CI, 0.48-1.55; P = .62) or median (interquartile range) length of stay (3 [3-5] days for both groups; P = .27). Conclusions and Relevance: In this study, low-dose aspirin for the initial treatment of children with KD was not associated with fever recrudescence or coronary artery abnormalities. Given the potential benefits, further study of low-dose aspirin to detect potentially clinically relevant outcome differences is warranted to inform treatment decisions and guideline development.Item Correlation of inpatient and outpatient measures of stroke care quality within veterans health administration hospitals(2011-08) Ross, Joseph S.; Arling, Greg; Ofner, Susan; Roumie, Christianne L; Keyhani, Salomeh; Williams, Linda S.; Ordin, Diana L.; Bravata, Dawn M.Background and Purpose—Quality of care delivered in the inpatient and ambulatory settings may be correlated within an integrated health system such as the Veterans Health Administration. We examined the correlation between stroke care quality at hospital discharge and within 6 months postdischarge. Methods—We conducted a cross-sectional hospital-level correlation analyses of chart-abstracted data for 3467 veterans discharged alive after an acute ischemic stroke from 108 Veterans Health Administration medical centers and 2380 veterans with postdischarge follow-up within 6 months in fiscal year 2007. Four risk-standardized processes of care represented discharge care quality: prescription of antithrombotic and antilipidmic therapy, anticoagulation for atrial fibrillation, and tobacco cessation counseling along with a composite measure of defect-free care. Five risk-standardized intermediate outcomes represented postdischarge care quality: achievement of blood pressure, low-density lipoprotein, international normalized ratio, and glycosylated hemoglobin target levels, and delivery of appropriate treatment for poststroke depression along with a composite measure of achieved outcomes. Results—Median risk-standardized composite rate of defect-free care at discharge was 79%. Median risk-standardized postdischarge rates of achieving goal were 56% for blood pressure, 36% for low-density lipoprotein, 41% for international normalized ratio, 40% for glycosylated hemoglobin, and 39% for depression management and the median risk-standardized composite 6-month outcome rate was 44%. The hospital composite rate of defect-free care at discharge was correlated with meeting the low-density lipoprotein goal (r=0.31; P=0.007) and depression management (r=0.27; P=0.03) goal but was not correlated with blood pressure, international normalized ratio, glycosylated hemoglobin goals, nor with the composite measure of achieved postdischarge outcomes (probability values >0.13). Conclusions—Hospital discharge care quality was not consistently correlated with ambulatory care quality.Item Development and Testing of the Dysmenorrhea Symptom Interference (DSI) Scale(2020-07-17) Chen, Chen X.; Murphy, Tabitha; Ofner, Susan; Yahng, Lilian; Krombach, Peter; LaPradd, Michelle; Bakoyannis, Giorgos; Carpenter, Janet S.; School of NursingDysmenorrhea affects most reproductive-age women and increases the risk of future pain. To evaluate dysmenorrhea interventions, validated outcome measures are needed. In this two-phase study, we developed and tested the dysmenorrhea symptom interference scale. During the scale-development phase (n = 30), we created a nine-item scale based on qualitative data from cognitive interviews. During the scale-testing phase (n = 686), we evaluated reliability, validity, and responsiveness to change. The scale measures how dysmenorrhea symptoms interfere with physical, mental, and social activities. Internal consistency was strong with Cronbach's α > 0.9. Test-retest reliability was acceptable (r = 0.8). The scale showed satisfactory content validity, construct validity (supported by confirmatory factor analysis), concurrent validity, and responsiveness to change. The minimally important difference was 0.3 points on a scale with a possible total score ranging from 1 to 5. This new psychometrically sound scale can be used in research and clinical practice to facilitate the measurement and management of dysmenorrhea.Item Development and Validation of Electronic Quality Measures to Assess Care for Patients With Transient Ischemic Attack and Minor Ischemic Stroke(AHA, 2017) Bravata, Dawn M.; Myers, Laura J.; Cheng, Eric; Reeves, Mathew; Baye, Fitsum; Zhangsheng, Yu; Damush, Teresa; Miech, Edward J.; Sico, Jason; Phipps, Michael; Zillich, Alan; Johanning, Jason; Chaturvedi, Seemant; Austin, Curt; Ferguson, Jared; Maryfield, Bailey; Snow, Kathy; Ofner, Susan; Graham, Glenn; Rhude, Rachel; Williams, Linda S.; Arling, Greg; Medicine, School of MedicineBackground—Despite interest in using electronic health record (EHR) data to assess quality of care, the accuracy of such data is largely unknown. We sought to develop and validate transient ischemic attack and minor ischemic stroke electronic quality measures (eQMs) using EHR data. Methods and Results—A random sample of patients with transient ischemic attack or minor ischemic stroke, cared for in Veterans Health Administration facilities (fiscal year 2011), was identified. We constructed 31 eQMs based on existing quality measures. Chart review was the criterion standard for validating the eQMs. To evaluate eQMs in terms of eligibility, we calculated the proportion of patients who were genuinely not eligible to receive a process (based on chart review) and who were correctly identified as not eligible by the EHR data (specificity). To assess eQMs about classification of whether patients received a process, we calculated the proportion of patients who actually received the process (based on chart review) and who were classified correctly by the EHR data as passing (sensitivity). Seven hundred sixty-three patients were included. About eligibility, specificity varied from 25% (brain imaging; carotid imaging) to 99% (anticoagulation quality). About pass rates, sensitivity varied from 30% (antihypertensive class) to 100% (coronary risk assessment; international normalized ratio measured). The 16 eQMs with ≥70% specificity in eligibility and ≥70% sensitivity in pass rates included coronary risk assessment, international normalized ratio measured, HbA1c measurement, speech language pathology consultation, anticoagulation for atrial fibrillation, discharge on statin, lipid management, neurology consultation, Holter, deep vein thrombosis prophylaxis, oral hypoglycemic intensification, cholesterol medication intensification, antihypertensive intensification, antihypertensive class, carotid stenosis intervention, and substance abuse referral for alcohol. Conclusions—It is feasible to construct valid eQMs for processes of transient ischemic attack and minor ischemic stroke care. Healthcare systems with EHRs should consider using electronic data to evaluate care for their patients with transient ischemic attack and to complement and expand quality measurement programs currently focused on patients with stroke.Item Development, Validation, and Assessment of an Ischemic Stroke or Transient Ischemic Attack-Specific Prediction Tool for Obstructive Sleep Apnea(Elsevier, 2017-08) Sico, Jason J.; Yaggi, H. Klar; Ofner, Susan; Concato, John; Austin, Charles; Ferguson, Jared; Qin, Li; Tobias, Lauren; Taylor, Stanley; Vaz Fragoso, Carlos A.; McLain, Vincent; Williams, Linda S.; Bravata, Dawn M.; Biostatistics, School of Public HealthBACKGROUND: Screening instruments for obstructive sleep apnea (OSA), as used routinely to guide clinicians regarding patient referral for polysomnography (PSG), rely heavily on symptomatology. We sought to develop and validate a cerebrovascular disease-specific OSA prediction model less reliant on symptomatology, and to compare its performance with commonly used screening instruments within a population with ischemic stroke or transient ischemic attack (TIA). METHODS: Using data on demographic factors, anthropometric measurements, medical history, stroke severity, sleep questionnaires, and PSG from 2 independently derived, multisite, randomized trials that enrolled patients with stroke or TIA, we developed and validated a model to predict the presence of OSA (i.e., Apnea-Hypopnea Index ≥5 events per hour). Model performance was compared with that of the Berlin Questionnaire, Epworth Sleepiness Scale (ESS), the Snoring, Tiredness, Observed apnea, high blood Pressure, Body mass index, Age, Neck circumference, and Gender instrument, and the Sleep Apnea Clinical Score. RESULTS: The new SLEEP Inventory (Sex, Left heart failure, ESS, Enlarged neck, weight [in Pounds], Insulin resistance/diabetes, and National Institutes of Health Stroke Scale) performed modestly better than other instruments in identifying patients with OSA, showing reasonable discrimination in the development (c-statistic .732) and validation (c-statistic .731) study populations, and having the highest negative predictive value of all in struments. CONCLUSIONS: Clinicians should be aware of these limitations in OSA screening instruments when making decisions about referral for PSG. The high negative predictive value of the SLEEP INventory may be useful in determining and prioritizing patients with stroke or TIA least in need of overnight PSG.Item Diagnosing and managing sleep apnea in patients with chronic cerebrovascular disease: a randomized trial of a home-based strategy(Springer, 2017-07) Bravata, Dawn M.; McClain, Vincent; Austin, Charles; Ferguson, Jared; Burrus, Nicholas; Miech, Edward J.; Matthias, Marianne S.; Chumbler, Neale; Ofner, Susan; Foresman, Brian; Sico, Jason; Vaz Fragoso, Carlos A.; Williams, Linda S.; Agarwal, Rajiv; Concato, John; Yaggi, H. Klar; Department of Medicine, IU School of MedicineBackground Obstructive sleep apnea is common and associated with poor outcomes after stroke or transient ischemic attack (TIA). We sought to determine whether the intervention strategy improved sleep apnea detection, obstructive sleep apnea (OSA) treatment, and hypertension control among patients with chronic cerebrovascular disease and hypertension. Methods In this randomized controlled strategy trial intervention, patients received unattended polysomnography at baseline, and patients with OSA (apnea-hypopnea index ≥5 events/h) received auto-titrating continuous positive airway pressure (CPAP) for up to 1 year. Control patients received usual care and unattended polysomnography at the end of the study, to identify undiagnosed OSA. Both groups received 24-h blood pressure assessments at baseline and end of the study. “Excellent” CPAP adherence was defined as cumulative use of ≥4 h/night for ≥70% of the nights. Results Among 225 randomized patients (115 control; 110 intervention), 61.9% (120/194) had sleep apnea. The strategy successfully diagnosed sleep apnea with 97.1% (102/105) valid studies; 90.6% (48/53, 95% CI 82.7–98.4%) of sleep apnea was undiagnosed among control patients. The intervention improved long-term excellent CPAP use: 38.6% (22/57) intervention versus 0% (0/2) control (p < 0.0001). The intervention did not improve hypertension control in this population with well-controlled baseline blood pressure: intervention, 132.7 mmHg (±standard deviation, 14.1) versus control, 133.8 mmHg (±14.0) (adjusted difference, −1.1 mmHg, 95% CI (−4.2, 2.0)), p = 0.48). Conclusions Patients with cerebrovascular disease and hypertension have a high prevalence of OSA. The use of portable polysomnography, and auto-titrating CPAP in the patients’ homes, improved both the diagnosis and the treatment for sleep apnea compared with usual care but did not lower blood pressure.