The relationship between the morningness-eveningness questionnaire and incident cancer: A historical clinical cohort study.

OBJECTIVE: We conducted a retrospective cohort study to explore the relationship between chronotype measured by the total Morningness-Eveningness Questionnaire (MEQ) score and incident cancer. METHODS: We used clinical and provincial health administrative data on consecutive adults who underwent a Level 1 Polysomnography (PSG) and completed the MEQ between 2010 and 2015 in an academic hospital (Ontario, Canada) and were cancer-free at baseline. Cancer status was derived from the Ontario Cancer Registry. Individuals were followed until death or March 31, 2020. We used multivariable Cox cause-specific regressions to address the research objective. RESULTS: Of 3,004 individuals, 1,781 were analyzed: a median age of 54 years (IQR: 40-64) and 838 (47.1%) men. The median total MEQ score was 63 (IQR: 55-69); 61 (3.4%) were classified as evening (≤41), 536 (30.1%) as intermediate (42-58), and 1,184 (66.5%) as morning chronotypes (≥59). Over a median of 7 years (IQR: 5-8), 120 (6.7%) developed cancer. A U-shape relationship was found between the total MEQ score and an increased hazard of incident cancer, controlling for PSG measures of sleep apnea severity and sleep architecture, demographics, and comorbidities. Compared to the median of 63.0, a total MEQ score greater or less than the median was associated with an increased hazard of incident cancer, with the largest effect for those with a total score ≥76 (e.g., HR of a MEQ total score of 78 vs. 63: 2.01, 95% CI: 1.09-3.71). CONCLUSION: The U-shaped curve may reflect deviations from a standard circadian tendency, which may stress biological systems and influence malignancy risk.

Obstructive sleep apnea in those with idiopathic intracranial hypertension undergoing diagnostic in-laboratory polysomnography.

RATIONALE: The association of obstructive sleep apnea (OSA) with idiopathic intracranial hypertension (IIH) remains unclear, and few studies have used objective in-laboratory polysomnography (PSG) data. Thus, we used PSG data to examine the: 1) association between OSA, and its severity, with IIH and 2) sex differences in OSA severity in those with and without IIH. METHODS: We retrospectively analyzed diagnostic PSG data from January 2015 to August 2023 for patients who were diagnosed with IIH by a neuro-ophthalmologist using the modified Dandy criteria. We selected three age, sex, and body mass index (BMI) matched controls for each IIH patient. We examined potential associations of IIH with OSA using regression. Sex differences were analyzed using ANOVA. RESULTS: Of 3482 patients who underwent PSG, we analyzed 78 IIH patients (16 males) and 234 matched controls (48 males). Five (6.4 %) IIH and 39 (16.7 %) control patients had OSA, defined as AHI≥15. After adjusting for age, sex, BMI, and comorbidities, IIH was negatively associated with the presence of OSA (OR 0.29, 95%CI 0.10-0.87, p = 0.03). However, models that adjusted for acetazolamide use, with or without comorbidities, showed no significant relationship with OSA (OR 0.31, p = 0.20). Males with IIH had a significantly higher age (p = 0.020), OSA severity (p = 0.032), and arousal index (p = 0.046) compared to females with IIH. CONCLUSIONS: IIH treated with acetazolamide was not an independent risk factor for OSA presence or severity. The presence of IIH treated with acetazolamide likely does not warrant routine screening for OSA, but related risk factors may identify appropriate patients.

Polysomnographic Assessment of Sleep Disturbances in Cancer Development: A Historical Multicenter Clinical Cohort Study.

BACKGROUND: Many cellular processes are controlled by sleep. Therefore, alterations in sleep might be expected to stress biological systems that could influence malignancy risk. RESEARCH QUESTION: What is the association between polysomnographic measures of sleep disturbances and incident cancer, and what is the validity of cluster analysis in identifying polysomnography phenotypes? STUDY DESIGN AND METHODS: We conducted a retrospective multicenter cohort study using linked clinical and provincial health administrative data on consecutive adults free of cancer at baseline with polysomnography data collected between 1994 and 2017 in four academic hospitals in Ontario, Canada. Cancer status was derived from registry records. Polysomnography phenotypes were identified by k-means cluster analysis. A combination of validation statistics and distinguishing polysomnographic features was used to select clusters. Cox cause-specific regressions were used to assess the relationship between identified clusters and incident cancer. RESULTS: Among 29,907 individuals, 2,514 (8.4%) received a diagnosis of cancer over a median of 8.0 years (interquartile range, 4.2-13.5 years). Five clusters were identified: mild (mildly abnormal polysomnography findings), poor sleep, severe OSA or sleep fragmentation, severe desaturations, and periodic limb movements of sleep (PLMS). The associations between cancer and all clusters compared with the mild cluster were significant while controlling for clinic and year of polysomnography. When additionally controlling for age and sex, the effect remained significant only for PLMS (adjusted hazard ratio [aHR], 1.26; 95% CI, 1.06-1.50) and severe desaturations (aHR, 1.32; 95% CI, 1.04-1.66). Further controlling for confounders, the effect remained significant for PLMS, but was attenuated for severe desaturations. INTERPRETATION: In a large cohort, we confirmed the importance of polysomnographic phenotypes and highlighted the role that PLMS and oxygenation desaturation may play in cancer. Using this study's findings, we also developed an Excel (Microsoft) spreadsheet (polysomnography cluster classifier) that can be used to validate the identified clusters on new data or to identify which cluster a patient belongs to. TRIAL REGISTRY: ClinicalTrials.gov; Nos.: NCT03383354 and NCT03834792; URL: www. CLINICALTRIALS: gov.

Polysomnographic Markers of Obstructive Sleep Apnea Severity and Cancer-related Mortality: A Large Retrospective Multicenter Clinical Cohort Study.

Rationale: The evidence for an association between cancer survival and obstructive sleep apnea (OSA) remains underexplored. Objectives: To evaluate an association between markers of OSA severity (respiratory disturbances, hypoxemia, and sleep fragmentation) and cancer-related mortality in individuals with previously diagnosed cancer. Methods: We conducted a multicenter retrospective cohort study using linked clinical and provincial health administrative data on consecutive adults who underwent a diagnostic sleep study between 1994 and 2017 in four Canadian academic hospitals and were previously diagnosed with cancer through the Ontario Cancer Registry. Multivariable cause-specific Cox regressions were used to address the research objective. Results: We included 2,222 subjects. Over a median follow-up time of 5.6 years (interquartile range [IQR], 2.7-9.1 years), 261/2,222 (11.7%) individuals with prevalent cancer died from cancer-related causes, which accounted for 44.2% (261/590) of all-cause death. Controlling for age, sex, alcohol use disorder, prior heart failure, chronic obstructive pulmonary disease, hypertension, diabetes, treatment for OSA, clinic site, year of the sleep study, and time since the cancer diagnosis, measures of hypoxemia and sleep fragmentation, but not apnea-hypopnea index, were significantly associated with the cancer-specific mortality: percentage of time spent with arterial oxygen saturation (SaO2) < 90% (hazard ratio [HR] per 5% increase, 1.05; 95% confidence interval, 1.01-1.09); mean SaO2 (HR per 3% increase, 0.79; 0.68-0.92); and percentage of stage 1 sleep (HR per 16% increase, 1.27; 1.07-1.51). Conclusions: In a large clinical cohort of adults with suspected OSA and previously diagnosed cancer, measures of nocturnal hypoxemia and sleep fragmentation as markers of OSA severity were significantly associated with cancer-related mortality, suggesting the need for more targeted risk awareness.

Rapid Bedside Ultrasound Evaluation of a Ruptured Abdominal Aortic Aneurysm With a Prior Repair.

Ruptured aortic aneurysms carry a high risk of morbidity and mortality, particularly if not rapidly identified. We present an 87-year-old male, with a history of hypertension and prior endovascular aortic repair, who presented to the Emergency Department (ED) with several days of epigastric abdominal pain radiating to his back and flanks. The patient acutely deteriorated in the ED, and point-of-care ultrasound rapidly identified active extravasation from an abdominal aortic aneurysm with visualization of prior endograft. Point-of-care ultrasound in this patient expedited the diagnosis, resuscitation, and transfer to the operating room with definitive repair by vascular surgery. The patient recovered and was discharged in stable condition.

Lupus podocytopathy superimposed on diabetic glomerulosclerosis: A case report.

RATIONALE: Lupus podocytopathy (LP) is an entity that is increasingly being reported in the literature on systemic lupus erythematosus (SLE). LP is characterized by nephrotic syndrome in SLE patients with diffuse glomerular podocyte foot process effacement and no immune complex deposits along the capillary loops. Histologically, LP typically mimics minimal change disease or primary focal segmental glomerulosclerosis (FSGS) on a background of ISN/RPS class I or II lupus nephritis. In situations where there are coexistent glomerular diseases, however, LP may be easily masked by background lesions and overlapping clinical symptoms. PATIENT CONCERNS: We report the case of a 24-year-old woman with type I diabetes, hypertension, psoriasis/rash, and intermittent arthritis who presented with abrupt onset of severe nephrotic proteinuria and renal insufficiency. Renal biopsy revealed nodular glomerulosclerosis and FSGS. Immune deposits were not identified by immunofluorescence or electron microscopy. Ultrastructurally, there was diffuse glomerular basement membrane thickening and over 90% podocyte foot process effacement. With no prior established diagnosis of SLE, the patient was initially diagnosed with diabetic nephropathy with coexistent FSGS, and the patient was started on angiotensin-converting enzyme inhibitors (ACEI) and diuretics. However, nephrotic proteinuria persisted and renal function deteriorated. The patient concurrently developed hemolytic anemia with pancytopenia. DIAGNOSES: Subsequent to the biopsy, serologic results showed positive autoantibodies against double strand DNA (dsDNA), Smith antigen, ribonucleoprotein (RNP), and Histone. A renal biopsy was repeated, revealing essentially similar findings to those of the previous biopsy. Integrating serology and clinical presentation, SLE was favored. The pathology findings were re-evaluated and considered to be most consistent with LP and coexistent diabetic nephropathy, with superimposed FSGS either as a component of LP or as a lesion secondary to diabetes or hypertension. INTERVENTIONS: The patient was started on high-dose prednisone at 60 mg/day, with subsequent addition of mycophenolate mofetil and ACEI, while prednisone was gradually tapered. OUTCOMES: The patient's proteinuria, serum creatinine, complete blood counts, skin rash, and arthritis were all significantly improved. CONCLUSION: The diagnosis of LP when confounded by other glomerular diseases that may cause nephrotic syndrome can be challenging. Sufficient awareness of this condition is necessary for the appropriate diagnosis and treatment.

Factors associated with seizure development after bupropion overdose: a review of the toxicology investigators consortium.

BACKGROUND: Bupropion is an aminoketone antidepressant. A major concern in bupropion toxicity is seizure activity, which can occur up to 24 h from ingestion. It is difficult to predict which patients will have seizures. The purpose of this study is to identify clinical features associate with seizure after bupropion overdose. METHODS: We searched the Toxicology Investigators Consortium registry for a cases of poisoning by bupropion between January 1, 2014 and January 1, 2017 in patients aged 13-65. Demographic variables and clinical features were compared between patients who did and did not experience a seizure and presented as unadjusted odds ratios (OR). Multivariable logistic regression was used to calculate adjusted odds ratios (aOR) between clinical features and seizures. RESULTS: There were 256 cases of bupropion overdose remaining after inclusion/exclusion criteria were applied. Clinical features associated with seizure were QTc >500 (OR = 3.4, 95% CI: 1.3-8.8, p = 0.012), tachycardia (p > 140) (OR = 1.9, 95% CI: 1-3.561, p = 0.05), and age 13-18 years (2.4, 95% CI: 1.3-4.3, p = 0.005). The mean QTc value for patients experiencing a seizure was 482 ms (N = 95 IQR: 59 ms) versus 454 ms (N = 103, IQR: 43) in patients who did not experience seizure, however, it was not possible to identify a QTc cutoff with sensitivity or specificity to predict seizures. CONCLUSION: Based on our analysis of data from the ToxIC registry, age (13-18), tachycardia (p > 140) and QTc >500 ms are associated with seizures in bupropion overdose; however, a specific QTc value may not be a useful predictor of seizures.

Radiation Emergency Readiness Among US Medical Toxicologists: A Survey.

INTRODUCTION: Large scale radiologic and nuclear disasters are rare; however, recent events such as the Fukushima Daiichi nuclear reactor emergency in Japan and current global political tensions have highlighted the need for health-care providers with expertise in managing radiation injuries. Medical Toxicologists have the ability to collaborate with other specialists in filling this critical role. METHODS: We conducted a cross-sectional survey to assess the attitudes, experiences, and knowledge of medical toxicologists through the assistance of the American College of Medical Toxicology. RESULTS: The survey was completed by 114 medical toxicologists during the enrollment period. Medical toxicologists who had a willingness to participate in radiologic or nuclear emergencies or who had taken care of patients contaminated with radioactive material were more likely to perform well on the knowledge assessment. CONCLUSION: We identified that there is a group of medical toxicologists who have the willingness, experience, and knowledge to help manage patients in the event of a radiologic or nuclear emergency.

Obstructive Sleep Apnea and Incident Cancer: A Large Retrospective Multicenter Clinical Cohort Study.

BACKGROUND: To examine the association between the severity of obstructive sleep apnea (OSA) and nocturnal hypoxemia with incident cancer. METHODS: This was a multicenter retrospective clinical cohort study using linked clinical and provincial health administrative data on consecutive adults who underwent a diagnostic sleep study between 1994 and 2017 in four academic hospitals (Canada) who were free of cancer at baseline. Cancer status was derived from the Ontario Cancer Registry. Cox cause-specific regressions were utilized to address the objective and to calculate the 10-year absolute risk difference (ARD) in the marginal probability of incident cancer and the number needed to harm (NNH). RESULTS: Of 33,997 individuals considered, 33,711 with no missing OSA severity were included: median age, 50 years; 58% male; and 23% with severe OSA (apnea-hypopnea index >30). Of the 18,458 individuals with information on sleep time spent with oxygen saturation (SaO2) <90%, 5% spent >30% of sleep with SaO2 <90% (severe nocturnal hypoxemia). Over a median of 7 years, 2,498 of 33,711 (7%) individuals developed cancer, with an incidence rate of 10.3 (10.0-10.8) per 1,000 person-years. Controlling for confounders, severe OSA was associated with a 15% increased hazard of developing cancer compared with no OSA (HR = 1.15, 1.02-1.30; ARD = 1.28%, 0.20-2.37; and NNH = 78). Severe hypoxemia was associated with about 30% increased hazard (HR = 1.32, 1.08-1.61; ARD = 2.38%, 0.47-4.31; and NNH = 42). CONCLUSIONS: In a large cohort of individuals with suspected OSA free of cancer at baseline, the severity of OSA and nocturnal hypoxemia was independently associated with incident cancer. IMPACT: These findings suggest the need for more targeted cancer risk awareness in individuals with OSA.

Two Cases of Serotonin Syndrome After Bupropion Overdose Treated With Cyproheptadine.

BACKGROUND: Bupropion is not known to have direct serotonin agonism or inhibit serotonin reuptake. In spite of this, it has been implicated as a causative agent of serotonin syndrome. We highlight two cases of single-agent bupropion overdose that subsequently met the diagnosis of serotonin syndrome by the Hunter criteria, despite the absence of direct serotonergic agents. CASE 1: A 14-year-old boy intentionally ingested an estimated 30 bupropion 75-mg immediate-release tablets. He presented in status epilepticus, was intubated, and was placed on midazolam and fentanyl infusions. He developed tremor, ankle clonus, and agitation. He was administered cyproheptadine for presumed serotonin syndrome with temporal improvement in his symptoms. CASE 2: A 19-year-old woman intentionally ingested an estimated 53 bupropion 150-mg extended-release tablets. She had a seizure and required sedation and intubation. During her course, she developed hyperthermia, inducible clonus, and hyperreflexia. She was treated with cyproheptadine without temporal improvement of symptoms but improved the following day. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although bupropion is not known to be directly serotonergic, it has been implicated as the single causative agent after overdose. This may be due to an indirect increase in activity of serotonergic cells. In these cases, bupropion overdose resulted in a clinical presentation consistent with serotonin syndrome, with the first having a temporal improvement after treatment with cyproheptadine. Physicians need to be aware of the potential serotonergic activity of bupropion for accurate assessment and treatment of this dangerous condition.

Ultrasound-assisted catheter-directed thrombolysis versus systemic anticoagulation alone for submassive pulmonary embolism.

Pulmonary embolism (PE) is a significant contributor to morbidity and mortality in the United States. Catheter-directed, ultrasound-assisted thrombolysis (USAT) uses high-frequency, low-energy ultrasound waves to disaggregate uncrosslinked fibrin fibers and increase thrombus penetration of a locally delivered thrombolytic to treat an acute PE. The purpose of this study is to compare the efficacy and safety of catheter-directed USAT versus systemic anticoagulation alone in submassive PE. This was a single-center, retrospective study of patients with a diagnosis of acute submassive PE from April 4, 2014 to May 1, 2019 at a large, academic medical center. Subjects were split into two different groups based on treatment with either USAT with systemic anticoagulation or systemic anticoagulation alone. The primary outcome was the incidence of severe or life-threatening GUSTO bleeding within 72 h or until hospital discharge if sooner. A total of 130 subjects were included (n = 40 in the USAT group and n = 90 in systemic anticoagulation alone group). Significantly fewer subjects in the USAT group had an active diagnosis of cancer at the time of presentation (7.5% vs 28.9%, p = 0.006). There was no difference in severe or life-threatening GUSTO bleeding or any component of the GUSTO bleeding definitions. Administration of USAT with systemic anticoagulation was well-tolerated when compared to systemic anticoagulation alone, but bias may have led to selection of patients for USAT with a lower bleeding risk and higher functional status at baseline.

Antibody-Negative Paraneoplastic Limbic Encephalitis, Parkinsonism, Hypothermia, and Narcolepsy Associated with Endometrial Carcinoma.

BACKGROUND: We describe the clinical and neuropathological features of a patient with T-cell-mediated paraneoplastic limbic encephalitis, parkinsonism, hypothermia, and narcolepsy-like presentation associated with endometrial carcinoma. OBJECTIVES: This patient with prominent parkinsonism and narcolepsy broadens the phenotype of known paraneoplastic syndromes and demonstrates the importance of investigation for occult malignancy even in the absence of paraneoplastic antibodies. METHODS: This is a case report with diagnosis confirmed at postmortem. RESULTS: Paraneoplastic antibodies were not detected. The initial improvement with immunosuppression was short lived, and postmortem neuropathological examination demonstrated encephalitis with predominant T-cell infiltration affecting the hypothalamus and extending to the brainstem, suggestive of a paraneoplastic syndrome. CONCLUSIONS: Although the possibility of a novel antibody cannot be ruled out, consideration must also be given to recent demonstration of purely T-cell-mediated neuronal destruction in the context of paraneoplastic syndromes.

Predictors of in-laboratory polysomnography attendance in a cohort of patients with stroke or TIA.

STUDY OBJECTIVES: After cerebrovascular events, obstructive sleep apnea (OSA) is associated with poor functional outcomes, an increased risk of recurrent stroke, and mortality. Although the significant under-diagnosis of OSA is likely multifactorial in nature, factors associated with attendance at in-laboratory polysomnography (iPSG) are poorly understood. We evaluated demographic, lifestyle, and clinical variables that predicted attendance at iPSG in a cohort of patients with stroke and transient ischemic attack (TIA) enrolled in a clinical research study. METHODS: Demographic, lifestyle, and clinical variables were summarized for the patients who did and did not attend iPSG. Multivariable binary logistic regression analyses were performed to examine four models that thematically aggregated predictors expected to relate to attendance. Further, t-tests for continuous variables, and chi-squared tests for categorical variables, were performed to uncover differences between the two groups. RESULTS: In the 122 participants included in our analyses, mean age was 66.6 ± 15.7 (64.8% males) with only 59.0% of participants attending iPSG. Only Model 1, which investigated the impact of demographic, lifestyle, and cognitive status, was significant (χ2 = 35.31, p < 0.001). Among our variables, (1) younger age, (2) better cognition, (3) higher level of education, and (4) never-smoking status significantly predicted attendance at iPSG. CONCLUSION: By understanding the relationship between variables that significantly predict attendance, we hope our results will translate into practices that promote iPSG attendance, which may help improve outcomes in the stroke/TIA population. CLINICAL TRIALS: SLEep APnea Screening Using Mobile Ambulatory Recorders After TIA/Stroke (SLEAP SMART) (NCT02454023); https://clinicaltrials.gov/ct2/show/NCT02454023.

Single-Agent Bupropion Exposures: Clinical Characteristics and an Atypical Cause of Serotonin Toxicity.

INTRODUCTION: Bupropion is the only Food and Drug Administration-approved synthetic cathinone. It increases the release of norepinephrine in the locus coeruleus and dorsal raphe nucleus, causing an increase in the frequency of serotonergic neuron firing. The diagnosis of serotonin toxicity (ST) from bupropion poisoning is controversial due to the lack of direct serotonergic activity. Nonetheless, there is one documented report of ST after single-agent bupropion overdose and multiple reports describing polypharmacy overdoses where bupropion may have contributed to ST. METHODS: This is a retrospective analysis of data collected by the Toxicology Investigators Consortium (ToxIC), a prospective multi-center toxico-surveillance and research network registry, from 2014 to 2017. Cases were identified if ST was a clinical effect and bupropion was the single agent listed. Data is presented descriptively. RESULTS: Of the 266 recorded single bupropion overdoses, the most common symptoms were seizures (47.1%), tachycardia (greater than 140 bpm) (33.9%), agitation (31.7%), toxic psychosis (20.4%), and myoclonus/tremor/hyperreflexia (19%). Benzodiazepines were the most common therapy (69.2%). Thirteen patients (5.9%) were diagnosed with ST by a medical toxicologist. CONCLUSION: Bupropion overdose is primarily associated with seizures, tachycardia, and agitation; bupropion may be an atypical cause of serotonin toxicity.

Analysis of electrooculography signals for the detection of Myasthenia Gravis.

OBJECTIVE: A precursor to more severe forms of Myasthenia Gravis (MG) is ocular MG (OMG) in which the MG symptoms are localized to the eyes. Current MG diagnostic methods are often invasive, painful, and not always specific. The objective of the proposed work was to extract quantifiable features from electrooculography (EOG) signals recorded around the eyes and develop an alternative non-invasive screening method for detecting MG. METHODS: EOG signals acquired from MG and Control subjects were analyzed for eye movement characteristics and quantified using time and wavelet domain signal processing techniques. The ability of the proposed approaches to classify MG vs. control subjects was evaluated using a linear discriminant analysis (LDA) based classifier. RESULTS: The range of overall classification accuracies achieved by the proposed time and wavelet domain approaches for different groupings were between 82.1-83.3% (Rise Rate feature: P < 0.01, AUC ≥ 0.87) and 82.1-87.2% (Mean Scale Band Energy feature: P < 0.01, AUC ≥ 0.89), respectively. CONCLUSION: Our results demonstrate that an EOG-based signal analysis is a potentially viable non-invasive alternative for MG screening. SIGNIFICANCE: The proposed approach could lead to early detection of MG and thereby improve clinical outcomes in this population.

Screening for Post-Stroke Depression and Cognitive Impairment at Baseline Predicts Long-Term Patient-Centered Outcomes After Stroke.

BACKGROUND: Independence and reintegration into community roles are important patient-centered outcomes after stroke. Depression and cognitive impairment are common post-stroke conditions that may impair long-term function even years after a stroke. However, screening for these post-stroke comorbidities remains infrequent in stroke prevention clinics and the utility of this screening for predicting long-term higher-level function has not been evaluated. AIMS: To evaluate the ability of a validated brief Depression, Obstructive sleep apnea, and Cognitive impairment screen (DOC screen) to predict long-term (2-3 years after stroke) community participation and independence in instrumental activities of daily living post stroke. METHODS: One hundred twenty-four patients (mean age, 66.3 [standard deviation = 15.7], 52.4% male) completed baseline depression and cognitive impairment screening at first stroke clinic visit, and telephone interviews 2 to 3 years post stroke to assess community independence (Frenchay Activities Index [FAI]) and participation (Reintegration to Normal Living Index [RNLI]). A subset of these patients also consented to complete detailed neuropsychological testing at baseline. Univariate and multivariate linear (FAI) and logistic (RNLI) regression analyses were used to determine the individual relationship between baseline data (predictors) and follow-up scores. RESULTS: Older age (ß = -0.17, P = .001), greater stroke severity (ß = 1.84, P = .015), more depressive (ß = -2.41, P = .023), and cognitive (ß = -2.15, P = .046) symptoms independently predicted poor instrumental activity ( R2 = .27; P < .001). Measures of executive dysfunction were the strongest correlates of poor instrumental activity. Higher depression risk was the only significant predictor of participation on the RNLI in regression modeling (odds ratio = 0.46, P = .028). CONCLUSIONS: Baseline DOC screening in stroke prevention clinics shows that symptoms of depression and cognitive impairment are independent predictors of impaired higher-level functioning and community reintegration 2 to 3 years after stroke. Novel rehabilitation and psychological interventions targeting people with these conditions are needed to improve long-term patient-centered outcomes.