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Item Association between admission haematocrit and mortality among men with acute ischaemic stroke(BMJ, 2018-04-24) Sico, Jason J.; Myers, Laura J.; Fenton, Brenda; Concato, John; Williams, Linda S.; Bravata, Dawn M.; Neurology, School of MedicineObjective: Anaemia is associated with higher mortality among patients with non-stroke cardiovascular conditions; less is known regarding the relationship between anaemia and mortality among patients with acute ischaemic stroke. Methods: Medical records were abstracted for n=3965 veterans from 131 Veterans Health Administration facilities who were admitted with ischaemic stroke in fiscal year 2007. Haematocrit values within 24 hours of admission were classified as ≤27%, 28%-32%, 33%-37%, 38%-42%, 43%-47% or ≥48%. Multivariate logistic regression was used to examine the relationship between anaemia and in-hospital, 30-day, 6-month and 1-year mortality, adjusting for age, medical comorbidities, modified Acute Physiology and Chronic Health Evaluation-III and stroke severity. Impact factors were calculated to standardise comparisons between haematocrit tier and other covariates. Results: Among n=3750 patients included in the analysis, the haematocrit values were ≤27% in 2.1% (n=78), 28%-32% in 6.2% (n=234), 33%-37% in 17.9% (n=670), 38%-42% in 36.4% (n=1366), 43%-47% in 28.2% (n=1059) and ≥48% in 9.1% (n=343). Patients with haematocrit ≤27%, compared with patients in the 38%-42% range, were more likely to have died across all follow-up intervals, with statistically significant adjusted ORs (aORs) ranging from 2.5 to 3.5. Patients with polycythaemia (ie, haematocrit ≥48%) were at increased risk of in-hospital mortality (aOR=2.9; 95% CI 1.4 to 6.0), compared with patients with mid-range admission haematocrits. Pronounced differences between patients receiving and not receiving blood transfusion limited our ability to perform a propensity analysis. Impact factors in the 1-year mortality model were 0.46 (severe anaemia), 0.06 (cancer) and 0.018 (heart disease). Conclusions: Anaemia is independently associated with an increased risk of death throughout the first year post stroke; high haematocrit is associated with early poststroke mortality. Severe anaemia is associated with 1-year mortality to a greater degree than cancer or heart disease. These data cannot address the question of whether interventions targeting anaemia might improve patient outcomes.Item Auto-titrating continuous positive airway pressure for patients with acute transient ischemic attack: a randomized feasibility trial(Ovid Technologies Wolters Kluwer -American Heart Association, 2010-07) Bravata, Dawn M.; Concato, John; Fried, Terri; Ranjbar, Noshene; Sadarangani, Tanesh; McClain, Vincent; Struve, Frederick; Zygmunt, Lawrence; Knight, Herbert J.; Lo, Albert; Richerson, George B.; Gorman, Mark; Williams, Linda S.; Brass, Lawrence M.; Agostini, Joseph; Mohsenin, Vahid; Roux, Francoise; Klar Yaggi, H.; Department of Medicine, IU School of MedicineBACKGROUND AND PURPOSE: Transient ischemic attack (TIA) patients are at risk of recurrent vascular events. The primary objectives were to evaluate among TIA patients the prevalence of sleep apnea and among patients with sleep apnea auto-titrating continuous positive airway pressure (auto-CPAP) adherence. The secondary objective was to describe among TIA patients with sleep apnea the recurrent vascular event rate by auto-CPAP use category. METHODS: All intervention patients received auto-CPAP for 2 nights, but only intervention patients with evidence of sleep apnea received auto-CPAP for the remainder of the 90-day period. Intervention patients received polysomnography at 90 days after TIA. Control patients received polysomnography at baseline and at 90 days. Acceptable auto-CPAP adherence was defined as >or=4 hours per night for >or=75% of nights. Vascular events included recurrent TIA, stroke, hospitalization for congestive heart failure, myocardial infarction, or death. RESULTS: We enrolled 70 acute TIA patients: 45 intervention and 25 control. The majority of patients had sleep apnea: 57% at baseline and 59% at 90 days. Among the 30 intervention patients with airflow obstruction, 12 (40%) had acceptable auto-CPAP adherence, 18 (60%) had some use, and none had no use. Three intervention patients (12%) had recurrent events compared with 1 (2%;P=0.13) control patient. The vascular event rate was highest among sleep apnea patients with no CPAP use: none, 16%;some, 5%;acceptable adherence 0% (P=0.08). CONCLUSIONS: Sleep apnea is common among acute TIA patients. It appears feasible to provide auto-CPAP in the acute TIA period. Larger studies should evaluate whether a strategy of diagnosing and treating sleep apnea can reduce recurrent vascular events after TIA.Item The Determining Risk of Vascular Events by Apnea Monitoring (DREAM) Study: Design, Rationale and Methods(Springer, 2016-05) Koo, Brian B.; Won, Christine; Selim, Bernardo J.; Qin, Li; Jeon, Sangchoon; Redeker, Nancy S.; Bravata, Dawn M.; Strohl, Kingman P.; Concato, John; Yaggi, Henry K.; Department of Neurology, IU School of MedicinePurpose The goal of the Determining Risk of Vascular Events by Apnea Monitoring (DREAM) study is to develop a prognostic model for cardiovascular outcomes, based on physiologic variables—related to breathing, sleep architecture, and oxygenation—measured during polysomnography in US veterans. Methods The DREAM study is a multi-site, retrospective observational cohort study conducted at three Veterans Affairs (VA) centers (West Haven, CT; Indianapolis, IN; Cleveland, OH). Veterans undergoing polysomnography between January 1, 2000 and December 31, 2004 were included based on referral for evaluation of sleep-disordered breathing, documented history and physical prior to sleep testing, and ≥2-h sleep monitoring. Demographic, anthropomorphic, medical, medication, and social history factors were recorded. Measures to determine sleep apnea, sleep architecture, and oxygenation were recorded from polysomnography. VA Patient Treatment File, VA–Medicare Data, Vista Computerized Patient Record System, and VA Vital Status File were reviewed on dates subsequent to polysomnography, ranging from 0.06 to 8.8 years (5.5 ± 1.3 years; mean ± SD). Results The study population includes 1840 predominantly male, middle-aged veterans. As designed, the main primary outcome is the composite endpoint of acute coronary syndrome, stroke, transient ischemic attack, or death. Secondary outcomes include incidents of neoplasm, congestive heart failure, cardiac arrhythmia, diabetes, depression, and post-traumatic stress disorder. Laboratory outcomes include measures of glycemic control, cholesterol, and kidney function. (Actual results are pending.) Conclusions This manuscript provides the rationale for the inclusion of veterans in a study to determine the association between physiologic sleep measures and cardiovascular outcomes and specifically the development of a corresponding outcome-based prognostic model.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.Item Diagnosing and Treating Sleep Apnea in Patients With Acute Cerebrovascular Disease(American Heart Association, 2018-08-21) Bravata, Dawn M.; Sico, Jason; Vaz Fragoso, Carlos A.; Miech, Edward J.; Matthias, Marianne S.; Lampert, Rachel; Williams, Linda S.; Concato, John; Ivan, Cristina S.; Fleck, J.D.; Tobias, Lauren; Austin, Charles; Ferguson, Jared; Radulescu, Radu; Iannone, Lynne; Ofner, Susan; Taylor, Stanley; Qin, Li; Won, Christine; Yaggi, H. Klar; Medicine, School of MedicineBackground Obstructive sleep apnea ( OSA ) is common among patients with acute ischemic stroke and transient ischemic attack. We evaluated whether continuous positive airway pressure for OSA among patients with recent ischemic stroke or transient ischemic attack improved clinical outcomes. Methods and Results This randomized controlled trial among patients with ischemic stroke/transient ischemic attack compared 2 strategies (standard or enhanced) for the diagnosis and treatment of OSA versus usual care over 1 year. Primary outcomes were National Institutes of Health Stroke Scale and modified Rankin Scale scores. Among 252 patients (84, control; 86, standard; 82, enhanced), OSA prevalence was as follows: control, 69%; standard, 74%; and enhanced, 80%. Continuous positive airway pressure use occurred on average 50% of nights and was similar among standard (3.9±2.1 mean hours/nights used) and enhanced (4.3±2.4 hours/nights used; P=0.46) patients. In intention-to-treat analyses, changes in National Institutes of Health Stroke Scale and modified Rankin Scale scores were similar across groups. In as-treated analyses among patients with OSA, increasing continuous positive airway pressure use was associated with improved National Institutes of Health Stroke Scale score (no/poor, -0.6±2.9; some, -0.9±1.4; good, -0.3±1.0; P=0.0064) and improved modified Rankin Scale score (no/poor, -0.3±1.5; some, -0.4±1.0; good, -0.9±1.2; P=0.0237). In shift analyses among patients with OSA, 59% of intervention patients had best neurological symptom severity (National Institutes of Health Stroke Scale score, 0-1) versus 38% of controls ( P=0.038); absolute risk reduction was 21% (number needed to treat, 4.8). Conclusions Although changes in neurological functioning and functional status were similar across the groups in the intention-to-treat analyses, continuous positive airway pressure use was associated with improved neurological functioning among patients with acute ischemic stroke/transient ischemic attack with OSAItem A multidisciplinary stroke clinic for outpatient care of veterans with cerebrovascular disease(2011-04) Schmid, Arlene A.; Kapoor, John R; Miech, Edward J.; Kuehn, Deborah; Dallas, Mary I; Kerns, Robert D; Lo, Albert C.; Concato, John; Phipps, Michael S.; Couch, Cody D; Moran, Eileen; Williams, Linda S.; Goble, Layne A; Bravata, Dawn M.Background: Managing cerebrovascular risk factors is complex and difficult. The objective of this program evaluation was to assess the effectiveness of an outpatient Multidisciplinary Stroke Clinic model for the clinical management of veterans with cerebrovascular disease or cerebrovascular risk factors. Methods: The Multidisciplinary Stroke Clinic provided care to veterans with cerebrovascular disease during a one-half day clinic visit with interdisciplinary evaluations and feedback from nursing, health psychology, rehabilitation medicine, internal medicine, and neurology. We conducted a program evaluation of the clinic by assessing clinical care outcomes, patient satisfaction, provider satisfaction, and costs. Results: We evaluated the care and outcomes of the first consecutive 162 patients who were cared for in the clinic. Patients had as many as six clinic visits. Systolic and diastolic blood pressure decreased: 137.2 ± 22.0 mm Hg versus 128.6 ± 19.8 mm Hg, P = 0.007 and 77.9 ± 14.8 mm Hg versus 72.0 ± 10.2 mm Hg, P = 0.004, respectively as did low-density lipoprotein (LDL)-cholesterol (101.9 ± 23.1 mg/dL versus 80.6 ± 25.0 mg/dL, P = 0.001). All patients had at least one major change recommended in their care management. Both patients and providers reported high satisfaction levels with the clinic. Veterans with stroke who were cared for in the clinic had similar or lower costs than veterans with stroke who were cared for elsewhere. Conclusion: A Multidisciplinary Stroke Clinic model provides incremental improvement in quality of care for complex patients with cerebrovascular disease at costs that are comparable to usual post-stroke care.Item Penetrance and Pleiotropy of Polygenic Risk Scores for Schizophrenia, Bipolar Disorder, and Depression Among Adults in the US Veterans Affairs Health Care System(American Medical Association, 2022-09-14) Bigdeli, Tim B.; Voloudakis, Georgios; Barr, Peter B.; Gorman, Bryan R.; Genovese, Giulio; Peterson, Roseann E.; Burstein, David E.; Velicu, Vlad I.; Li, Yuli; Gupta, Rishab; Mattheisen, Manuel; Tomasi, Simone; Rajeevan, Nallakkandi; Sayward, Frederick; Radhakrishnan, Krishnan; Natarajan, Sundar; Malhotra, Anil K.; Shi, Yunling; Zhao, Hongyu; Kosten, Thomas R.; Concato, John; O'Leary, Timothy J.; Przygodzki, Ronald; Gleason, Theresa; Pyarajan, Saiju; Brophy, Mary; Huang, Grant D.; Muralidhar, Sumitra; Gaziano, J. Michael; Aslan, Mihaela; Fanous, Ayman H.; Harvey, Philip D.; Roussos, Panos; Cooperative Studies Program (CSP); Million Veteran Program (MVP); Psychiatry, School of MedicineImportance: Serious mental illnesses, including schizophrenia, bipolar disorder, and depression, are heritable, highly multifactorial disorders and major causes of disability worldwide. Objective: To benchmark the penetrance of current neuropsychiatric polygenic risk scores (PRSs) in the Veterans Health Administration health care system and to explore associations between PRS and broad categories of human disease via phenome-wide association studies. Design, setting, and participants: Extensive Veterans Health Administration's electronic health records were assessed from October 1999 to January 2021, and an embedded cohort of 9378 individuals with confirmed diagnoses of schizophrenia or bipolar 1 disorder were found. The performance of schizophrenia, bipolar disorder, and major depression PRSs were compared in participants of African or European ancestry in the Million Veteran Program (approximately 400 000 individuals), and associations between PRSs and 1650 disease categories based on ICD-9/10 billing codes were explored. Last, genomic structural equation modeling was applied to derive novel PRSs indexing common and disorder-specific genetic factors. Analysis took place from January 2021 to January 2022. Main outcomes and measures: Diagnoses based on in-person structured clinical interviews were compared with ICD-9/10 billing codes. PRSs were constructed using summary statistics from genome-wide association studies of schizophrenia, bipolar disorder, and major depression. Results: Of 707 299 enrolled study participants, 459 667 were genotyped at the time of writing; 84 806 were of broadly African ancestry (mean [SD] age, 58 [12.1] years) and 314 909 were of broadly European ancestry (mean [SD] age, 66.4 [13.5] years). Among 9378 individuals with confirmed diagnoses of schizophrenia or bipolar 1 disorder, 8962 (95.6%) were correctly identified using ICD-9/10 codes (2 or more). Among those of European ancestry, PRSs were robustly associated with having received a diagnosis of schizophrenia (odds ratio [OR], 1.81 [95% CI, 1.76-1.87]; P < 10-257) or bipolar disorder (OR, 1.42 [95% CI, 1.39-1.44]; P < 10-295). Corresponding effect sizes in participants of African ancestry were considerably smaller for schizophrenia (OR, 1.35 [95% CI, 1.29-1.42]; P < 10-38) and bipolar disorder (OR, 1.16 [95% CI, 1.11-1.12]; P < 10-10). Neuropsychiatric PRSs were associated with increased risk for a range of psychiatric and physical health problems. Conclusions and relevance: Using diagnoses confirmed by in-person structured clinical interviews and current neuropsychiatric PRSs, the validity of an electronic health records-based phenotyping approach in US veterans was demonstrated, highlighting the potential of PRSs for disentangling biological and mediated pleiotropy.Item Prevalence, predictors, and outcomes of poststroke falls in acute hospital setting(2010) Schmid, Arlene A.; Wells, Carolyn K; Concato, John; Dallas, Mary I; Lo, Albert C.; Nadeau, Steven E; Williams, Linda S.; Peixoto, Aldo J; Gorman, Mark; Boice, John L.; Struve, Frederick; McClain, Vincent; Bravata, Dawn M.Abstract—Falls are a serious medical complication following stroke. The objectives of this study were to (1) confirm the prevalence of falls among patients with stroke during acute hospitalization, (2) identify factors associated with falls during the acute stay, and (3) examine whether in-hospital falls were associated with loss of function after stroke (new dependence at discharge). We completed a secondary analysis of data from a retrospective cohort study of patients with ischemic stroke who were hospitalized at one of four hospitals. We used logistic regression to identify factors associated with inpatient falls and examine the association between falls and loss of function. Among 1,269 patients with stroke, 65 (5%) fell during the acute hospitalization period. We found two characteristics independently associated with falls: greater stroke severity (National Institutes of Health Stroke Scale [NIHSS] 8, adjusted odds ratio [OR] = 3.63, 95% confidence interval [CI]: 1.46–9.00) and history of anxiety (adjusted OR = 4.90, 95% CI: 1.70–13.90). Falls were independently associated with a loss of function (adjusted OR = 9.85, 95% CI: 1.22–79.75) even after adjusting for age, stroke severity, gait abnormalities, and past stroke. Stroke severity (NIHSS 8) may be clinically useful during the acute inpatient setting in identifying those at greatest risk of falling. Given the association between falls and poor patient outcomes, rehabilitation interventions should be implemented to prevent falls poststroke.Item Receipt of cardiac screening does not influence 1-year post-cerebrovascular event mortality(Wolters Kluwer, 2018-06) Sico, Jason J.; Baye, Fitsum; Myers, Laura J.; Concato, John; Ferguson, Jared; Cheng, Eric M.; Jadbabaie, Farid; Yu, Zhangsheng; Arling, Gregory; Zillich, Alan J.; Reeves, Matthew J.; Williams, Linda S.; Bravata, Dawn M.; Biostatistics, School of Public HealthBackground: American Heart Association/American Stroke Association expert consensus guidelines recommend consideration of cardiac stress testing to screen for occult coronary heart disease (CHD) among patients with ischemic stroke/TIA who have a high-risk Framingham Cardiac Risk Score (FCRS). Whether this guideline is being implemented in routine clinical practice, and the association of its implementation with mortality, is less clear. Methods: Study participants were Veterans with stroke/TIA (n = 11,306) during fiscal year 2011 who presented to a VA Emergency Department or who were admitted. Patients were excluded (n = 6,915) based on prior CHD/angina/chest pain history, receipt of cardiac stress testing within 18 months prior to cerebrovascular event, death within 90 days of discharge, discharge to hospice, transfer to a non-VA acute care facility, or missing/unknown race. FCRS ≥20% was classified as high risk for CHD. ICD-9 and Common Procedural Terminology codes were used to identify receipt of any cardiac stress testing. Results: Among 4,391 eligible patients, 62.8% (n = 2,759) had FCRS ≥20%. Cardiac stress testing was performed infrequently and in similar proportion among high-risk (4.5% [123/2,759]) vs low/intermediate-risk (4.4% [72/1,632]) patients (adjusted odds ratio [aOR] 0.77, 95% confidence interval [CI] 0.54-1.10). Receipt of stress testing was not associated with reduced 1-year mortality (aOR 0.59, CI 0.26-1.30). Conclusions: In this observational cohort study of patients with cerebrovascular disease, cardiac screening was relatively uncommon and was not associated with 1-year mortality. Additional work is needed to understand the utility of CHD screening among high-risk patients with cerebrovascular disease.