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To explore the relationship between polysomnography-derived respiratory indices and chronic pain status among individuals following traumatic brain injury (TBI).Participants (n = 66) with moderate to severe TBI underwent polysomnography during inpatient acute rehabilitation and their chronic pain status was assessed at 1- to 2-year follow-up as part of the TBI Model Systems Pain Collaborative Study. Pairwise comparisons across pain cohorts (ie, chronic pain, no history of pain) were made to explore differences on polysomnography indices.Among our total sample, approximately three-quarters (74.2%) received sleep apnea diagnoses utilizing American Academy of Sleep Medicine criteria, with 61.9% of those endorsing a history of chronic pain. Of those endorsing chronic pain, the average pain score was 4.8 (standard deviation = 2.1), with a mean interference score of 5.3 (2.7). Pairwise comparisons revealed that those endorsing a chronic pain experience at follow-up experienced categorically worse indicators of sleep-related breathing disorders during acute rehabilitation relative to those who did not endorse chronic pain. Important differences were observed with elevations on central (chronic pain: 2.6; no pain: 0.8 per hour) and obstructive apnea (chronic pain: 15.7; no pain: 11.1 per hour) events, as well as oxygen desaturation indices (chronic pain: 19.6; no pain: 7.9 per hour).Sleep-disordered breathing appears worse among those who endorse chronic pain following moderate-to-severe TBI, but additional research is needed to understand its relation to postinjury pain. Prospective investigation is necessary to determine how clinical decisions (eg, opioid therapy) and intervention (eg, positive airway pressure) may mutually influence outcomes.Registry: ClinicalTrials.gov; Name: Comparison of Sleep Apnea Assessment Strategies to Maximize TBI Rehabilitation Participation and Outcome (C-SAS); URL: https://clinicaltrials.gov/ct2/show/NCT03033901; Identifier: NCT03033901.Martin AM, Pinto SM, Tang X, et al. Associations between early sleep-disordered breathing following moderate-to-severe traumatic brain injury and long-term chronic pain status: a Traumatic Brain Injury Model Systems study.

Introduction Sleep disturbance and chronic pain are very common after moderate to severe traumatic brain injury (msTBI). Despite having a bidirectional and mutually exacerbating relationship, there is a dearth of literature examining factors involved in the sleep-pain relationship following msTBI. Psychiatric symptoms (e.g., post-traumatic stress, depression) are also prevalent following injury and know to be related to sleep, as well as poor adjustment to chronic pain. The purpose of this study was to examine associations between sleep, psychiatric symptoms, and pain-beliefs among msTBI survivors who have comorbid chronic pain. Methods This is a secondary analysis of TBI Model Systems study data of 1,567 individuals reporting chronic pain after msTBI (M=8.5 years, SD=7.1). Participants were 46.8 years old on average (SD=27.9), predominantly male (72.7%) and completed measures of sleep (Pittsburgh Sleep Quality Index; PSQI), post-traumatic stress disorder (PTSD Checklist; PCL-5), depression (Patient Health Questionnaire; PHQ-9), anxiety (General Anxiety Disorder; GAD-7), pain-related catastrophizing (Coping Strategies Questionnaire; CSQ) and self-efficacy (Pain Self-Efficacy Questionnaire; PSEQ-2). Measures were adjusted for overlapping constructs. Relationships between sleep, psychiatric symptoms and pain beliefs were examined through Pearson correlations. Results Average PSQI total score for our sample was 8.78 (SD=4.4), indicating poor sleep quality, with an estimated 6.40 (SD=1.9) hours of sleep on average. Over two-third (68.5%) of our sample attributed some of their sleep disturbance to chronic pain and nearly half (47.4%) met cutoff (>8) for clinically significant poor sleep quality. PSQI scores were positively correlated with PCL (r = .44, p Conclusion Poorer sleep quality in individuals with chronic pain after msTBI is associated with more psychiatric symptoms, increased pain-related catastrophizing, and lower pain self-efficacy. Results highlight sleep quality as an important modifiable target for intervention in this at-risk clinical population and suggest that behavioral treatments to improve psychiatric comorbidities and adjustment to pain may be beneficial. Support (if any) National Institute on Disability, Independent Living, and Rehabilitation Research (NCT03033901).

Introduction Poor sleep quality and chronic pain are common after moderate-to-severe traumatic brain injury (msTBI). Prior studies have not examined the role of PTSD symptoms in the relationship between sleep quality and chronic pain experience (i.e., severity and pain-related interference) in those with msTBI. Yet, PTSD is known to be associated with both sleep and pain. The purpose of this analysis is to determine the role of PTSD symptoms in the sleep-pain relationship among this at-risk clinical population. Methods Secondary analyses were performed on data (n=1537) from the TBI Model Systems follow-up study. Participants were an average age of 46.21 years old, predominantly male (72.61%), and followed at an average of 8.5 years post injury. Participants completed measures of sleep quality (Pittsburgh Sleep Quality Index; PSQI), pain severity and interference (Brief Pain Inventory; BPI), depression (Patient Health Questionnaire-9; PHQ-9) and PTSD symptoms (PTSD Checklist, PCL-5). Analysis of covariance (ANCOVA) was used to examine differences in pain outcomes controlling for relevant covariates, adjusting for item redundancy prior to analyses. Results Sleep quality and pain interference are associated such that “good sleepers” (PSQI≤8, mean=4.92±2.17) have lower pain interference scores than “poor sleepers” (PSQI>8, mean=12.63±2.87), with a mean pain interference of 3.41±2.32 vs 5.26±2.45 (p< 0.0001). “Good sleepers” also had lower pain severity (4.22±1.78 vs 5.28±1.84, p< 0.0001), lower PTSD symptoms (14.62±13.46 vs 28.35±17.82, p< 0.0001), and less depression symptoms (5.32±4.97 vs 10.57±6.22, p< 0.0001) when compared to “poor sleepers.” Pain interference and severity were significantly related to all covariates at a Conclusion In patients with msTBI, sleep quality and pain interference are positively associated such that better sleep quality corresponds with lower pain interference, a relationship which remains when controlling for PTSD and multiple covariates. Addressing the sleep needs of patients with msTBI through behavioral intervention (e.g., cognitive behavioral therapy for insomnia), even in the presence of additional psychiatric comorbidities, may assist those who experience chronic pain following injury. Support (if any)

Introduction Previous studies have shown automatic scoring of portable level 3 sleep study provides similar findings when compared to polysomnography (PSG), establishing home sleep apnea tests (HSAT) as an adequate screening tool for OSA. Accuracy of level 3 studies with Nox T3 portable sleep studies (Noxturna Inc., Atlanta GA) may improve with manual editing to include total sleep time (TST). No other studies have compared unedited versus manually edited HSAT with level 1 in-lab PSG performed simultaneously. This study evaluates if added manual editing optimizes the diagnostic accuracy of HSAT in classifying the severity of OSA, using both AASM and CMS criteria. Methods Secondary analysis of six-center (n=206) sleep apnea diagnostic comparative effectiveness trial. Participants underwent simultaneous administration of level 1 PSG (Philips Alice 6 LDx Diagnostic Sleep system) and Nox T3 portable sleep study with centralized scoring using AASM and CMS criteria. All HSAT were autoscored and then edited by the registered polysomnographic technician. Editing entailed establishing start and stop recording times based on accompanying actigraphy data (reduction in movement) in the portable device and elimination of recording artifact. Results Using AASM criteria, poor sensitivity OSA (AHI≥5) was observed using unedited vs PSG (p=.01) compared to manually edited HSAT vs. PSG (p=.06). No statistically significant difference was observed using AHI≥15 or via categorization across four levels of OSA (none, mild, moderate, or severe). In contrast, CMS criteria comparisons to PSG showed poor specificity of OSA (AHI≥5) for unedited (p=.003) compared to edited (p=.372) HSAT studies. As expected, total sleep time was overestimated using T3 actigraphy devices compared to the criterion standard across both edited and unedited studies (p=.001, .001 respectively). Conclusion Improvements in sensitivity and specificity of OSA were noted using edited versus unedited T3 HSAT when compared to Level 1 PSG using both AASM and CMS criteria. Results support need for manualized editing of HSAT in persons with hospitalized TBI. Support (if any) PCORI (CER-1511-33005), GDHS (W91YTZ-13-C-0015)

Objective To describe the cost benefit of 4 different approaches to screening for sleep apnea in a cohort of participants with moderate to severe traumatic brain injury (TBI) receiving inpatient rehabilitation from the payor’s perspective. Design A cost-benefit analysis of phased approaches to sleep apnea diagnosis. Setting Six TBI Model System Inpatient Rehabilitation Centers. Participants Trial data from participants (N=214) were used in analyses (mean age 44±18y, 82% male, 75% white, with primarily motor vehicle–related injury [44%] and falls [33%] with a sample mean emergency department Glasgow Coma Scale of 8±5). Intervention Not applicable. Main Outcome Cost benefit. Results At apnea-hypopnea index (AHI) ≥15 (34%), phased modeling approaches using screening measures (Snoring, Tired, Observed, Blood Pressure, Body Mass Index, Age, Neck Circumference, and Gender [STOPBANG] [–$5291], Multivariable Apnea Prediction Index MAPI [–$5262]) resulted in greater cost savings and benefit relative to the portable diagnostic approach (–$5210) and initial use of laboratory-quality polysomnography (–$5,011). Analyses at AHI≥5 (70%) revealed the initial use of portable testing (–$6323) relative to the screening models (MAPI [–$6250], STOPBANG [–$6237) and initial assessment with polysomnography (–$5977) resulted in greater savings and cost-effectiveness. Conclusions The high rates of sleep apnea after TBI highlight the importance of accurate diagnosis and treatment of this comorbid disorder. However, financial and practical barriers exist to obtaining an earlier diagnosis during inpatient rehabilitation hospitalization. Diagnostic cost savings are demonstrated across all phased approaches and OSA severity levels with the most cost-beneficial approach varying by incidence of OSA.

Objective The purpose of this study was to describe incidence and assess predictors of adherence to Positive Airway Pressure (PAP) therapy for Obstructive Sleep Apnea (OSA) in persons with acquired brain injury (ABI). Methods A 2012–2015 retrospective analysis of consecutive ABI patients admitted for neurorehabilitation, referred for polysomnography (PSG), and prescribed PAP for OSA. Univariable linear regressions were conducted to examine predictors of average hours of nightly PAP use. Univariable logistic regressions were conducted to examine predictors of PAP adherence using the conventional clinical definition of ≥4 h per night ≥70% of the time. Persons with traumatic etiology were separately analyzed. Results ABI etiology was 51% traumatic, 36% stroke, and 13% other nontraumatic causes. Nearly two-thirds were nonadherent to PAP. For the overall sample, higher average nightly PAP usage was significantly predicted by positive hypertension diagnosis (β = 0.271, p = 0.019). Likewise, greater adherence based on the conventional cutoff was predicted by poorer motor functioning at hospital admission (OR = 0.98, p = 0.001) and lower oxygen saturation nadir (OR = 0.99, p = 0.003). For those with traumatic injuries, greater adherence was predicted by poorer functional status at hospital admission (OR = 0.98, p = 0.010) and positive hypertension diagnosis (OR = 0.16, p = 0.023). Conclusions In this study of hospitalized neurorehabilitation patients with ABI and comorbid OSA, predictors of adherence included lower oxygen saturation, poorer functional status and hypertension diagnosis, perhaps signifying the role of greater severity of illness on treatment adherence. High rates of refusal and nonadherence to frontline PAP therapy for sleep apnea is a concern for persons in recovery form ABI who are at a time of critical neural repair.

Objective To determine the diagnostic sensitivity and specificity and comparative effectiveness of traditional sleep apnea screening tools in traumatic brain injury (TBI) neurorehabilitation admissions. Design Prospective diagnostic comparative effectiveness trial of sleep apnea screening tools relative to the criterion standard, attended level 1 polysomnography including encephalography. Setting Six TBI Model System Inpatient Rehabilitation Centers. Participants Between May 2017 and February 2019, 449 of 896 screened were eligible for the trial with 345 consented (77% consented). Additional screening left 263 eligible for and completing polysomnography with final analyses completed on 248. Intervention Not applicable. Main Outcome Measures Area under the curve (AUC) of screening tools relative to total apnea hypopnea index≥15 (AHI, moderate to severe apnea) measured at a median of 47 days post-TBI (interquartile range, 29-47). Results The Berlin high-risk score (receiving operating curve [ROC] AUC=0.634) was inferior to the Multivariable Apnea Prediction Index (MAPI) (ROC AUC=0.780) (P=.0211; CI, 0.018-0.223) and Snoring, Tired, Observed, Blood Pressure, Body Mass Index, Age, Neck Circumference, and Gender (STOPBANG) score (ROC AUC=0.785) (P=.001; CI, 0.063-0.230), both of which had comparable AUC (P=.7245; CI, −0.047 to 0.068). Findings were similar for AHI≥30 (severe apnea); however, no differences across scales was observed at AHI≥5. The pattern was similar across TBI severity subgroups except for posttraumatic amnesia (PTA) status wherein the MAPI outperformed the Berlin. Youden's index to determine risk yielded lower sensitivities but higher specificities relative to non-TBI samples. Conclusion This study is the first to provide clinicians with data to support a choice for which sleep apnea screening tools are more effective during inpatient rehabilitation for TBI (STOPBANG, MAPI vs Berlin) to help reduce comorbidity and possibly improve neurologic outcome.

Objectives To describe patient and clinical characteristics associated with receipt of opioid medications and identify differences in sleep quality, architecture, and sleep-related respiration between those receiving and not receiving opioid medications. Setting Acute inpatient rehabilitation care for moderate to severe traumatic brain injury (TBI). Participants A total of 248 consecutive admissions for inpatient rehabilitation care following moderate to severe TBI (average age of 43.6 years), who underwent level 1 polysomnography (PSG) (average time since injury: 120 days) across 6 sites. Design Cross-sectional, secondary analyses. Main measures The PSG sleep parameters included total sleep time (TST), sleep efficiency (SE), wake after sleep onset, rapid eye movement (REM) latency, sleep staging, and arousal and awakening indices. Respiratory measures included oxygen saturation, central apnea events per hour, obstructive apnea and hypopnea events per hour, and total apnea-hypopnea index. Results After adjustment for number of prescribed medication classes, those receiving opioid medications on the day of PSG experienced increased TST relative to those not receiving opioid medications (estimated mean difference [EMD] = 31.58; 95% confidence interval [CI], 1.9-61.3). Other indices of sleep did not differ significantly between groups. Among respiratory measures those receiving opioids on the day of PSG experienced increased frequency of central sleep apnea events during total (EMD = 2.92; 95% CI, 0.8-5.0) and non-REM sleep (EMD = 3.37; 95% CI, 1.0-5.7) and higher frequency of obstructive sleep apnea events during REM sleep (EMD = 6.97; 95% CI, 0.1-13.8). Compared with those who did not, receiving opioids was associated with lower oxygen saturation nadir during total sleep (EMD = -3.03; 95% CI, -5.6 to -0.4) and a greater number of oxygen desaturations across REM (EMD = 8.15; 95% CI, 0.2-16.1), non-REM (EMD = 7.30; 95% CI, 0.3-14.4), and total sleep (EMD = 8.01; 95% CI, 0.8-15.2) Greater total apnea-hypopnea index was observed during REM (EMD = 8.13; 95% CI, 0.8-15.5) and total sleep (EMD = 7.26; 95% CI, 0.08-14.4) for those receiving opioids. Conclusion Opioid use following moderate to severe TBI is associated with an increase in indicators of sleep-related breathing disorders, a modifiable condition that is prevalent following TBI. As sleep-wake disorders are associated with poorer rehabilitation outcomes and opioid medications may frequently be administered following traumatic injury, additional longitudinal investigations are warranted in determining whether a causal relation between opioids and sleep-disordered breathing in those following moderate to severe TBI exists. Given current study limitations, future studies can improve upon methodology through the inclusion of indication for and dosage of opioid medications in this population when examining these associations.

Background OSA is prevalent during a time of critical neural repair after traumatic brain injury (TBI). The diagnostic utility of existing sleep studies is needed to inform clinical management during acute recovery from TBI. Research Question This study aimed to evaluate the non-inferiority and diagnostic accuracy of a portable level 3 sleep study relative to level 1 polysomnography in hospitalized neurorehabilitation patients with TBI. Study Design and Methods This is a prospective clinical trial conducted at six TBI Model System study sites between May 2017 and February 2019. Of 896 admissions, 449 were screened and eligible for the trial, with 345 consented. Additional screening left 263 eligible for and completing simultaneous administration of both level 1 and level 3 sleep studies, with final analyses completed on 214 (median age = 42 years; ED Glasgow Coma Scale = 6; time to polysomnography [PSG] = 52 days). Results Agreement was moderate to strong (weighted kappa = 0.78, 95% CI, 0.72-0.83) with the misclassification commonly occurring with mild sleep apnea due to underestimation of apnea hypopnea index (AHI). Most of those with moderate to severe sleep apnea were correctly classified (n = 54/72). Non-inferiority was not demonstrated: the minimum tolerable specificity of 0.5 was achieved across all AHI cutoff scores (lower confidence limits [LCL] range, 0.807-0.943), but the minimum tolerable sensitivity of 0.8 was not (LCL range, 0.665-0.764). Interpretation Although the non-inferiority of level 3 portable diagnostic testing relative to level 1 was not established, strong agreement was seen across sleep apnea indexes. Most of those with moderate to severe sleep apnea were correctly identified; however, there was risk of misclassification with level 3 sleep studies underestimating disease severity for those with moderate to severe AHI and disease presence for those with mild AHI during early TBI neurorehabilitation.

Survivors of brain injury who have disorders of consciousness often have chronic functional deficits and disability. Obstructive sleep apnoea, a sleep-related breathing disorder, is a medical comorbid condition common among persons with brain injury and is injurious to health. Research on obstructive sleep apnoea treatment among brain-injured patients-particularly persons with disorders of consciousness-is sparse. This case study describes a patient with severe brain injury admitted for neurorehabilitation in a minimally conscious state. Obstructive sleep apnoea was identified and treated. Treatment compliance was variable, and functional motor and cognitive improvement were observed during periods of better compliance. Study design does not permit casual attribution for functional improvement, but identification and treatment of obstructive sleep apnoea are suggested as a possible way to promote recovery after brain injury.

Background Although patients with acute myeloid leukemia (AML) were shown to have an increased risk of thrombosis, no thrombosis risk assessment scoring system has been developed for AML patients. The Khorana Risk Score (KRS), which has been widely used for thrombosis risk assessment in the clinical setting, was developed on the basis of solid tumor data and has not been validated among AML patients. This study aims to validate the use of the KRS as a thrombosis risk-scoring system among patients with AML. Methods Using data from H. Lee Moffitt Cancer Center and Research Institution’s Total Cancer Care Research Study, we retrospectively identified patients who were histologically confirmed with AML from 2000 to 2018. Clinical and laboratory variables at the time of AML diagnosis were characterized and analyzed. The thrombotic event rate was estimated with the Kaplan-Meier method and compared using the log-rank test. Results A total of 867 AML patients were included in the analysis. The median age at AML diagnosis was 75 years (range, 51–96), and the majority were male (65%, n = 565). A total of 22% (n = 191), 51% (n = 445), 24% (n = 207), and 3% (n = 24) of patients had a KRS of 0, 1, 2, and 3, respectively. A total of 42 thrombotic events (3% [n = 6/191] with a KRS of 1; 5% [n = 23/445] with a KRS of 2; 6.3% [n = 13/207] with a KRS of 3) were observed, with a median follow-up of 3 months (range, 0.1–307). There was no statistical difference in the risk of thrombosis between these groups (P = .1949). Conclusions Although there was an increased risk of thrombosis associated with a higher KRS among AML patients with a KRS of 1 to 3, the difference was not statistically significant. Furthermore, only a few patients were found to have a KRS > 3, and this was largely due to pancytopenia, which is commonly associated with AML. These results indicate the need for a better thrombotic risk-scoring system for AML patients.

Background Sleep problems and disorders are prevalent in patients with traumatic brain injury (TBI) and are associated with negative outcomes. Incidence varies because of challenges including differences in assessment methods, particularly in the acute stages of recovery when patients are cognitively impaired and unable to complete traditional self-report methods. Actigraphy (ACG) recently has been validated in the acute TBI rehabilitation setting and may serve as a superior method of assessing sleep-wake patterns at this stage of recovery. Although a few studies with small sample sizes have described the use of ACG, none have described feasibility and implementation protocols. Objective To describe the feasibility and implementation protocol of ACG to evaluate sleep-wake patterns and white-light exposure data in patients with acute TBI during inpatient rehabilitation. Sleep-wake patterns and light exposure data are presented to characterize the sample using these methods to inform future research. Design Retrospective study. Setting Acute inpatient rehabilitation unit at a Veterans' Affairs Polytrauma Rehabilitation Center. Participants Veterans (age ≥18 years) admitted to inpatient rehabilitation and enrolled in the Traumatic Brain Injury Model Systems study who were admitted and discharged in the calendar year 2013. Methods Veterans underwent actigraph watch placement as soon as possible after admission. Records from the calendar year 2013 were reviewed to determine the number of admissions that met study criteria and what percentage of those patients had 3 days of continuous ACG data collected. The barriers to successful watch placement in this population were reviewed. Average sleep, light, and wake data from available records were collected for the study sample. Main Outcome Measurements Percentage of patients who met study criteria and who had 72 hours of continuous ACG data collected. The barriers to successful watch placement in this population were reviewed. Average sleep, light, and wake data from available records were collected. Results Of 22 eligible Traumatic Brain Injury Model Systems admissions, 3 consecutive nights of ACG data were successfully obtained for 86% (n = 19) of the sample. Barriers to data collection included patient access due to abbreviated lengths of stay, staff availability for ACG placement, and data collection protocols to prevent loss of data in Veterans' Affairs computing systems. Conclusions ACG is feasible for collecting data about sleep, wake, and light exposure in patients who are in acute TBI inpatient rehabilitation settings. Level of Evidence III

Introduction Sleep-related breathing disorders are common after TBI. To date, two single site studies have reported divergent findings in post-TBI patients with one reporting predominantly obstructive sleep apnea (OSA, Holcomb et al., 2016) and the other central sleep apnea (CSA, Webster and Bell, 1998). The purpose of this analysis is to explore prevalence, demographics, and injury characteristics of patients with a clinical diagnosis of CSA in a recently-completed multicenter comparative-effectiveness trial during inpatient rehabilitation following moderate to severe TBI. Methods Participants in a six-center diagnostic comparative effectiveness trial underwent Level-1 polysomnography (PSG) during inpatient rehabilitation for TBI. Studies were scored at a centralized scoring center by one of two certified PSG technicians with final interpretation by a board-certified sleep medicine physician. Results 21 of 248 (8.5%) participants evidenced elevated CSA indices >5. Predominant CSA was rare (n=3 [1.2%], age range: 36-59; 100% male; 33-52 days post-TBI). One participant was on opioid, anti-depressant and antiepileptic drugs, one was on an antiepileptic, and another was on an opioid. PAP therapy was not initiated during PSG thus there was no treatment-emergent CSA. All had a central apnea-hypopnea index (AHI) in the moderate to severe range (29-49). Two out of the three had a GCS Conclusion In this multi-center clinical trial, predominant CSA was rare. The common practice of reducing polypharmacy in order to minimize sedation and optimize mental status in specialized inpatient brain-injury rehabilitation programs may contribute to the low CSA incidence in this cohort. Attention to medication side-effects and their influence on sleep-related breathing should be routinely considered. Support PCORI (CER-1511-33005), GDHS (W91YTZ-13-C-0015) for DVBIC, NIDILRR (90DPTB0008-03-00; 90DPTB0013-01-00).

OBJECTIVE To examine concordance of accelerometer-based actigraphy (ACG) with polysomnography (PSG) in the determination of sleep states in inpatients with traumatic brain injury (TBI), and examine the impact of injury severity and comorbid conditions (spasticity, apnea) on concordance. PARTICIPANTS This was a convenience sample of 50 participants with primarily severe TBI. DESIGN This was a retrospective chart review of concurrent administration of PSG with ACG in nonconsecutive rehabilitation admissions with TBI. MAIN MEASURES Total sleep time and sleep efficiency were measured by PSG and ACG. RESULTS Moderate to strong correlations between ACG and PSG were observed for total sleep time (r = 0.78, P < .01) and sleep efficiency (r = 0.66, P < .01). PSG and ACG estimates of total sleep time (316 minutes vs 325 minutes, respectively) and sleep efficiency (78% vs 77%, respectively) were statistically indistinguishable. CONCLUSIONS Actigraphy is a valid proxy for monitoring of sleep in this population across injury severity and common comorbidity groups. However, further research with larger sample sizes to examine concordance in patients with TBI with disorder of consciousness and spasticity is recommended.

OBJECTIVE To prospectively examine the incidence and risk factors for sleep apnea in consecutive brain injury rehabilitation admissions. SETTING Inpatient neurorehabilitation hospital. PARTICIPANTS Participants (n = 86) were consecutive neurorehabilitation admissions. DESIGN Retrospective analysis of prospectively collected data. MAIN MEASURES Polysomnography. RESULTS Half (49%) of the sample was diagnosed with sleep apnea. For the full sample, univariate logistic regression revealed age (odds ratio: 1.08; 95% confidence interval: 1.04-1.11) and hypertension (odds ratio: 7.77; 95% confidence interval: 2.81-21.47) as significant predictors of sleep apnea diagnosis. Results of logistic regression conducted within the traumatic brain injury group revealed age (odds ratio: 1.07; 95% confidence interval: 1.02-1.13) as the only significant predictor of apnea diagnosis after adjustment for other variables. Hierarchical generalized linear regression models for the prediction of apnea severity (ie, apnea-hypopnea index found that Functional Independence Measure Cognition Score (P = .01) and age (P < .01) were significant predictors. Following adjustment for all other terms, only age (P < .01) remained significant. CONCLUSION Sleep apnea is prevalent in acute neurorehabilitation admissions and traditional risk profiles for sleep apnea may not effectively screen for the disorder. Given the progressive nature of obstructive sleep apnea and morbidity associated with even mild obstructive sleep apnea, early identification and intervention may address comorbidities influencing acute and long-term outcome.

INTRODUCTION: Both solid and hematologic malignancies are associated with an increased risk of thromboembolic events, according to previous studies. One of the most common risk scoring systems was developed based on type of non-hematologic cancer, body mass index (BMI), WBC, hemoglobin, and platelet counts. However, compared to other solid tumors, acute leukemia patients commonly present with pancytopenia at the time of diagnosis and the Khorana Risk Score (KRS) has not been validated in patients with acute myeloid leukemia (AML). The goal of our study was to validate the KRS in AML patients. METHODS: Using Total Cancer Care (TCC), we retrospectively identified histologically confirmed AML patients from 2000 to 2018. Clinical and laboratory variables including age, gender, previous cancer history, use of growth factors, underlying coagulopathy, white blood cell counts, hemoglobin, and platelet counts were characterized at the time of AML diagnosis and annotated using descriptive statistics. The thrombotic event rate was estimated with the Kaplan-Meier method and compared using log-rank test. All statistical analyses were performed using SPSS v24.0 and GraphPad Prism 7. RESULTS: A total of 867 AML patients were included in this study. The median age at AML diagnosis was 75 (51-96) years and male patients were 65% (n=565). A total of 28% (n=241) patients had prior cancer history (hematologic malignancies, n=34; solid tumor, n=207). A total of 12% (n=101), 7% (n=58), and 1% (n=8) patients had EPO, G-CSF, GM-CSF treatment prior to AML diagnosis and 84% (n=728) patient were treated with any typed of growth factors after AML diagnosis. The median BMI was 27.1 (14.8-103) and 5% (n=47) patients had BMI higher than 35. A total of 26% (n=229) patients had WBC ≥11 x109/L (median 3.165 (0.08-413.74) x109/L), 67% (n=584) patients had hemoglobin 350 x109/L (median 46 (1-800) x109/L). A total of 22% (n=191) patients had Khorana score 0, 51% (n=445) patients had score 1, 24% (n=207) patients had score 2, and 3% (n=24) patients had score 3, respectively. A total of 42 thrombotic events were observed in the median follow up of 3 (0.1-307) months. Among these, a total of 3% (n=6/191), 5% (n=23/445), 6.3% (n=13/207), and 0% (n=0/24) thrombotic events occurred in patients with Khorana sore 0, 1, 2, and 3, respectively. Log-rank (Mantel-Cox) test showed no statistical difference between individual subgroup (p=0.1949). CONCLUSIONS: In AML patients, there was a higher incidence of thrombotic events in patients with higher Khorana score though the difference was not statistically significant. The proportion of patients with Khorana score ≥3 was relatively low, which could be due to pancytopenia, a common presentation in AML patients. These results suggest that the development of better thrombotic risk scoring system is warranted in patients with AML. Disclosures Komrokji: Celgene: Honoraria, Research Funding; Novartis: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau.

INTRODUCTION Thrombotic episodes represent significant morbidity and mortality in patients with hematologic malignancies and may be influenced by several risk factors. Current predictive and prognostic models do not take into account several risk factors. Furthermore, prophylactic and therapeutic management of thrombosis remains to be standardized for patients with AML. Few studies report the impact of catheters to the likelihood of thrombosis. We comprehensively report our institution's experience with thrombosis in AML patients. METHODS The Total Cancer Care (TCC) database was used to retrospectively chart review patients with histologically confirmed AML from 2000 to 2018. Several parameters were extracted including but not limited to history of thrombosis and recurrences, chemotherapy regimens, and laboratory values for significant events. All statistical analyses were performed using SPSS v24.0 and GraphPad Prism 7. RESULTS: A total of 1101 patients were diagnosed with either de novo (516, 46.87%) or secondary (584, 53.04%) AML. The median age of diagnosis was 75 years (52, 95) and men were the majority, 726 (65.94%). In terms of cytogenetics, 25 (2.27%) had good/favorable, 616 (55.95%) had intermediate, and 334 (41.75%) had poor cytogenetics. At the time of diagnosis, CBC revealed median WBC of 3 (0, 420), ANC 1 (0, 132), Plt 52 (1, 996), and hgb 9 (1, 15). Median ECOG score was 1. 159, 14.4% patients had a history of thrombosis prior to AML diagnosis; with a median of 1 episode of thrombosis (1, 4). After AML diagnosis 70 patients had one episode of thrombosis, 9 had two episodes, and 2 patients had three recurrent episodes. As far as the first-line induction therapy, 247 (22.43%) patients received 7+3, 12 (1.08%) received CLAG, 36 (3.27%) received hypomethylating agents, and the remaining 227 (2.06%) received other therapies such as clinical trials or off-label drugs. Repeat cycles of therapies were also recorded. In terms of growth factor use after AML diagnosis, 132 (11.99%) used EPO, 209 (18.98%) G-CSF, 32 (2.90%) GM-CSF, and 778 (70.66%) used any other growth factor not mentioned. Out of the 139 episodes of thrombosis, 81 (58.3%) were venous, and 58 (41.7%) were arterial. Among the venous, 45 (55.6%) were lower extremities, 21 (25.9%) were upper extremities, and 10 (12.3%) were pulmonary embolus. Among the arterial thrombosis, 27 (46.6) were coronary events, 23 (39.7%) were cerebral events. Only 15 patients had catheter-associated thrombosis events, 11 (73.3%) were PICC, and 2 (13.3%) were Port lines or central lines. In terms of management, 39 patients were on temporary anticoagulation, 60 patients were on indefinite anticoagulation, and 522 were not on any anticoagulation. In terms of complications, 3 patients had minor bleeding, 1 had major bleeding, 2 had HIT and the large majority of 419 had no complications of anticoagulation. CONCLUSIONS: Thrombosis both venous and arterial events manifest during treatment for leukemias. PICCs lines are associated with more catheter associated thrombosis events than ports. Further prospective studies are needed to evaluate the risk of both arterial and venous thrombosis in patients with acute leukemia. Further risk mitigation strategies are needed. Disclosures Komrokji: Novartis: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Speakers Bureau.

Objective:To assess the sustainability of an improvement in symptoms of depression using CPAP therapy in patients with obstructive sleep apnea.Patients/Methods:Patients referred to our center for e...

To assess the reversibility of symptoms of depression using continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea (OSA).Patients referred to our center for evaluation of OSA who had a respiratory disturbance index (RDI)or = 15 and who demonstrated a significant response to CPAP (or = 50% drop in RDI) were evaluated for the symptoms of depression using the Beck Depression Inventory (BDI), and then reassessed after 4 to 6 weeks of treatment with CPAP at home.In this group of patients, the institution of CPAP therapy resulted in a significant (p0.0001) decrease in those symptoms of depression as assessed by the BDI (BDI at baseline, 4.1 +/- 3.7; BDI after CPAP, 1.0 +/- 2.0). This change in BDI was noted both in those individuals who had received an antidepressant prescription prior to referral, and in those who had not. An analysis of variance failed to reveal any effect on these data related to gender or baseline RDI.Patients with OSA may present to their primary care physician with symptoms suggesting a diagnosis of depression. In some of these individuals, the symptoms of depression may be ameliorated with CPAP.

STUDY OBJECTIVE To identify the frequency and duration of those arousals exceeding fifteen seconds in length, in patients with obstructive sleep apnea. METHODS The polysomnographic tracings from fifty consecutive patients with obstructive sleep apnea were carefully analyzed to delineate the duration of each arousal event. These data were then collated to define the frequency of arousals of differing durations, and the impact thereof on the total time spent in an arousal state. RESULTS Respiratory event related prolonged arousals (> or = 15 seconds) were identified in 100% of the patients. These longer arousals accounted for 22% of all arousals, and 37% of all arousal time. The frequency of the arousals decreased with CPAP treatment, as did the time spent in an arousal state. CONCLUSIONS Patients with obstructive sleep apnea experience frequent respiratory event associated cortical arousals, many of which are greater than fifteen seconds in duration. There is the potential for these more prolonged arousals to be scored as epochs of Wake, which may result in their being reported as contributing to Wake After Sleep Onset (WASO) time, rather than as distinct arousals. This may result in an under-appreciation of both the frequency with which these prolonged arousals may occur, and the potential effect these arousals may have on the severity of the sleep fragmentation.

Uncontrolled bleeding remains the leading cause of preventable death in trauma. Hemostatic agents are effective in hemorrhage control but often fail following high-volume crystalloid resuscitation. Aggressive fluid resuscitation increases the blood pressure which may dislodge the newly formed clot causing rebleeding. The purpose of this study was to determine the systolic blood pressure (SBP) and the mean arterial pressure (MAP) at which rebleeding occurs when a clot is formed by one of these hemostatic agents (BleedArrest, TraumaDex, or Celox) compared to a control group. This was a prospective, experimental study using male 5 Yorkshire swine per group (BleedArrest, TraumaDex, Celox, or control). The femoral artery and vein were transected to simulate a traumatic injury. Subjects were allowed to bleed for 60 seconds then one of the agents was poured into the wound. The control group underwent the same procedures but without the hemostatic agent. After 30 minutes, dressings were removed and the SBP was increased incrementally using intravenous phenylephrine until rebleeding occurred or until the arterial blood pressure reached 210 mm/Hg. The SBP and MAP were significantly higher in the BleedArrest, TraumaDex, and Celox groups compared to a control group (p0.05).

Objective To prospectively characterize the prevalence, course, and impact of acute sleep abnormality among traumatic brain injury (TBI) neurorehabilitation admissions. Design Prospective observational study. Setting Freestanding rehabilitation hospital. Participants Primarily severe TBI (median emergency department Glasgow Coma Scale [GCS] score=7; N=205) patients who were mostly men (71%) and white (68%) were evaluated during acute neurorehabilitation. Interventions None. Main Outcome Measure Delirium Rating Scale-Revised-98 (DelRS-R98) was administered weekly throughout rehabilitation hospitalization. DelRS-R98 item 1 was used to classify severity of sleep-wake cycle disturbance (SWCD) as none, mild, moderate, or severe. SWCD ratings were analyzed both serially and at 1 month postinjury. Results For the entire sample, 66% (mild to severe) had SWCD at 1 month postinjury. The course of the SWCD using a subset (n=152) revealed that 84% had SWCD on rehabilitation admission, with 63% having moderate to severe ratings (median, 24d postinjury). By the third serial exam (median, 35d postinjury), 59% remained with SWCD, and 28% had moderate to severe ratings. Using general linear modeling and adjusting for age, emergency department GCS score, and days postinjury, presence of moderate to severe SWCD at 1 month postinjury made significant contributions in predicting duration of posttraumatic amnesia ( P P Conclusions Results suggest that sleep abnormalities after TBI are prevalent and decrease over time. However, a high percent remained with SWCD throughout the course of rehabilitation intervention. Given the brevity of inpatient neurorehabilitation, future studies may explore targeting SWCD to improve early outcomes, such as cognitive functioning and economic impact, after TBI.

This study sought to characterize mechanical activation in pulmonary arterial hypertension (PAH) using 2-dimensional echocardiography with tissue Doppler imaging. Whether pathologic alterations of the right ventricle in PAH affect interventricular dyssynchrony due to changes in mechanical activation of the septum and the right ventricle is unclear. We studied 20 patients with PAH (14 women, mean age 55 +/- 16 years) and 20 healthy controls (15 women, mean age 41 +/- 11 years) that underwent tissue Doppler imaging between July 2006 and May 2007. PAH was associated with accelerated right ventricular (RV) (p0.0001) and septal (p = 0.022) activation times, but no differences were found in lateral wall activation times between groups (p = 0.35). Measures of ventricular dyssynchrony indicated that patients with PAH had significantly lower RV-lateral wall delays (patients 3.2 +/- 66.2 ms vs controls 56.7 +/- 52.0 ms, p = 0.007), reflecting a faster activation of the right ventricle relative to the lateral wall than controls. In conclusion, PAH is associated with interventricular dyssynchrony manifested by accelerated RV free wall and septal activation times. Whether such dyssynchrony should serve as a therapeutic target remains to be determined.

To assess the sustainability of an improvement in symptoms of depression using CPAP therapy in patients with obstructive sleep apnea.Patients referred to our center for evaluation of obstructive sleep apnea who had a respiratory disturbance index (RDI) ofor =15 and who demonstrated a significant response to CPAP (50% or greater drop in RDI), were evaluated for symptoms of depression using the Beck Depression Inventory-Fast Screen for Medical Patients (BDI). These individuals were asked to complete the BDI assessment again after 4 to 6 weeks of treatment with CPAP (short-term follow-up), and then reassessed approximately one year later (long-term follow-up).In this group of patients, the institution of CPAP therapy resulted in a significant decrease in those symptoms of depression assessed by the BDI at both the short-term and long-term follow-up periods.For patients with OSA who continue CPAP therapy, we noted a statistically significant, sustained improvement in those symptoms of depression measured by the BDI.

To assess, in individuals referred for evaluation of obstructive sleep apnea, the potential clinical significance of brief versus longer arousals from sleep.Full-night polysomnographic tracings from 100 patients referred for evaluation of obstructive sleep apnea were analyzed to delineate the duration of each arousal event. These data were then correlated to the patient's subjective perception of sleepiness as estimated by the Epworth Sleepiness Scale (ESS).A significant relationship (p.0001, r(2) = .167) was noted between the frequency of the longer arousals (15 seconds) and the ESS. This relationship was significant, but distinctly weaker (p = .004, r(2) = .073), with the shorter arousals (3-15 seconds); moreover, the association with the brief arousals failed to remain significant (p = .678) after controlling for the effect of the longer arousals.Individuals with obstructive sleep apnea experience frequent respiratory event associated cortical arousals, many of which are greater than 15 seconds in duration. These longer arousals, which, in this study, constituted 18.4% of all arousals and accounted for 37.5% of the total arousal time, correlate more closely with the ESS than does the frequency or time attributable to the more numerous brief arousals. This suggests that these more-prolonged arousal events may have a greater impact on the restorative aspect of sleep, or on the perception thereof.

Pulse transit time (PTT) is a non-invasive index which reflects changes in peripheral vascular resistance and intrathoracic pressure. PTT arousal index (PTT Ar/I) is defined as the frequency (number/hour) of a defined decrease in PTT which may serve as a marker for respiratory events, and associated arousals which occur in patients with obstructive sleep apnea (OSA). This study was designed to evaluate the PTT Ar/I before and after patients with OSA were treated with continuous positive airway pressure (CPAP).Individuals referred for evaluation of possible OSA underwent split-night polysomnography (PSG). The findings from 144 consecutive patients with a respiratory disturbance index (RDI)/=20, who demonstrated at least a 50% drop in RDI with CPAP, provide the basis for this analysis. The PTT Ar/I measured before and after CPAP were compared to other measures of severity for OSA, including RDI and arousal index.The PTT Ar/I correlates with the RDI (r=0.43, P/=0.0001) and with the arousal index (r=0.43, P0.0001). Moreover, the decrease in RDI and arousal index that occurs with CPAP treatment correlates with a similar decrease in the PTT Ar/I (r=0.54, P0.0001).The PTT Ar/I correlates well with other standard measures of severity in patients with OSA and is potentially a non-invasive marker with which to measure the frequency of disruptive events that occur during sleep.

The investigators tested whether depressive symptoms were predictive of carotid atherosclerosis, a marker of coronary atherosclerosis. Healthy participants (n = 219) underwent the baseline assessment of cardiovascular risk factors, including self-reported depressive symptoms, and were assessed for carotid plaque at 10-year follow-up. Adjusting for baseline cardiovascular risk factors, participants with elevated depression scores at baseline were >2 times as likely as those with no depressive symptoms to have carotid plaque.