Circadian variation in stroke onset: Differences between ischemic and hemorrhagic stroke and weekdays versus weekends.

OBJECTIVES: To delineate diurnal variation onset distinguishing ischemic from hemorrhagic stroke, wake from sleep onset, and weekdays from weekends/holidays. MATERIALS AND METHODS: We analyzed patients enrolled in the FAST-MAG trial of field-initiated neuroprotective agent in patients with hyperacute stroke within 2h of symptoms onset. Stroke onset times were analyzed in 1h, 4h, and 12h time blocks throughout the 24h day-night cycle. Patient demographic, clinical features, stroke severity, and prehospital workflow were evaluated for association with onset times. RESULTS: Among 1615 acute cerebrovascular disease patients, final diagnoses were acute cerebral ischemia in 76.5% and Intracerebral hemorrhage in 23.5%. Considering all acute cerebrovascular disease patients, frequency of wake onset times showed a bimodal pattern, with peaks on onsets at 09:00-13:59 and 17:00-18:59 and early morning (00:00-05:59) onset in only 3.8%. Circadian rhythmicity differed among stroke subtypes: in acute cerebral ischemia, a single broad plateau of elevated incidences was seen from 10:00-21:59; in Intracerebral hemorrhage, bimodal peaks occurred at 09:00 and 19:00. The ratio of Intracerebral hemorrhage to acute cerebral ischemia occurrence was highest in early morning, 02:00-06:59. Marked weekday vs weekends pattern variation was noted for acute cerebral ischemia, with a broad plateau between 09:00 and 21:59 on weekdays but a unimodal peak at 14:00-15:59 on weekends. CONCLUSIONS: Wake onset of acute cerebrovascular disease showed a marked circadian variation, with distinctive patterns of a broad elevated plateau among acute cerebral ischemia patients; a bimodal peak among intracerebral hemorrhage patients; and a weekend change in acute cerebral ischemia pattern to a unimodal peak.

Prevalence and Predictors of Food Insecurity Among Stroke Survivors in the United States.

BACKGROUND: Food insecurity (FI)-lack of consistent access to food due to poor financial resources-limits the ability to eat a healthy diet, which is essential for secondary stroke prevention. Yet, little is known about FI in stroke survivors. METHODS: Using data from the US National Health and Nutrition Examination Survey from 1999 to 2015, we analyzed the prevalence, predictors, and temporal trends in FI among adults with and without self-reported prior stroke in this cross-sectional study. Age-standardized prevalence estimates were computed by self-reported history of stroke over survey waves. Multivariable logistic regression models were performed for the National Health and Nutrition Examination Survey participants who had a prior stroke to identify independent predictors of FI by self-reported history of stroke. RESULTS: Among 48 242 adults ≥20 years of age, 1877 self-reported history of stroke. FI was more prevalent among people with prior stroke (17%) versus those without prior stroke (12%; P<0.001). Prevalence of FI increased over time from 7.8% in 1999 to 42.1% in 2015 among stroke survivors and from 8% to 17% among individuals without prior stroke (P<0.001). The age-standardized prevalence of FI over the entire time was 24% among stroke survivors versus 11% among individuals without prior stroke (P<0.001). In the adjusted model, younger age (adjusted odds ratio [aOR], 0.96 [0.95-0.97]; P<0.01), Hispanic ethnicity (aOR, 2.12 [1.36-3.31]; P<0.01), lower education (aOR, 1.67 [1.17-2.38]; P<0.01), nonmarried status (aOR, 1.49 [1.01-2.19]; P=0.04), and poverty income ratio <130% (aOR, 3.78 [2.55-5.59]; P<0.01) were associated with FI in those with prior stroke. CONCLUSIONS: One in 3 stroke survivors reported FI in 2015, nearly double the prevalence in those without stroke. Addressing the fundamental drivers of FI and targeting vulnerable demographic groups may have a profound influence on stroke prevalence.

Association Between Glycemic Gap and In-hospital Outcomes in Aneurysmal Subarachnoid Hemorrhage.

Introduction: Glycemic gap (GG), as determined by the difference between glucose and the hemoglobin A1c (HbA1c)-derived estimated average glucose (eAG), is associated with poor outcomes in various clinical settings. There is a paucity of data describing GG and outcomes after aneurysmal subarachnoid hemorrhage (aSAH). Our main objectives were to evaluate the association of admission glycemic gap (aGG) with in-hospital mortality and with poor composite outcome and to compare aGG's predictive value to admission serum glucose. Secondary outcomes were the associations between aGG and neurologic complications including vasospasm and delayed cerebral ischemia following aSAH. Methods: We retrospectively reviewed 119 adult patients with aSAH admitted to a single tertiary care neuroscience ICU. Spearman method was used for correlation for non-normality of data. Area under the curve (AUC) for Receiver Operating Characteristic (ROC) curve was used to estimate prediction accuracy of aGG and admission glucose on outcome measures. Multivariable analyses were conducted to assess the value of aGG in predicting in-hospital poor composite outcome and death. Results: Elevated aGG at or above 30 mg/dL was identified in 79 (66.4%) of patients. Vasospasm was not associated with the elevated aGG. Admission GG correlated with admission serum glucose (r = 0.94, p < 0.01), lactate (r = 0.41, p < 0.01), procalcitonin (r = 0.38, p < 0.01), and Hunt and Hess score (r = 0.51, p < 0.01), but not with HbA1c (r = 0.02, p = 0.82). Compared to admission glucose, aGG had a statistically significantly improved accuracy in predicting inpatient mortality (AUC mean ± SEM: 0.77 ± 0.05 vs. 0.72 ± 0.06, p = 0.03) and trended toward statistically improved accuracy in predicting poor composite outcome (AUC: 0.69 ± 0.05 vs. 0.66 ± 0.05, p = 0.07). When controlling for aSAH severity, aGG was not independently associated with delayed cerebral ischemia, poor composite outcome, and in-hospital mortality. Conclusion: Admission GG was not independently associated with in-hospital mortality or poor outcome in a population of aSAH. An aGG ≥30 mg/dL was common in our population, and further study is needed to fully understand the clinical importance of this biomarker.

Admission glycemic gap in the assessment of patients with intracerebral hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) is the most common type of hemorrhagic stroke. Glycemic gap, determined by the difference between glucose and the HbA1c-derived average glucose, predicts poor outcomes in various clinical settings. Our main objective was to evaluate association of some admission factors and outcomes in relation to admission glycemic gap (AGG) in patients with ICH. METHODS: We retrospectively analyzed 506 adult patients with ICH between 2014 and 2019. AGG was defined as A1c-derived average glucose (28.7×HbA1c-46.7) subtracted from admission glucose. Admission factors and hospital outcomes indicative of poor outcome (i.e. death, gastrostomy tube, tracheostomy, and discharge status) were compared between patients with elevated (greater than 80 mg/dL) vs. non-elevated (less than or equal-to 80 mg/dL) AGG. Pearson chi-square test was used for independence, and multivariate analysis was used for association. SPSS and excel were used for all data analysis. RESULTS: We found that 67 of 506 (13%) ICH patients had elevated AGG with a mean of 137.3 mg/dL compared to 439 (87%) non-elevated AGG with a mean of 12.6 mg/dL. While mean and standard deviation values for age, weight,and body mass index were comparable between groups, the elevated AGG group had significantly higher admission glucose (286.1 ± 84.3 vs. 140.1 ± 42.5, p < 0.001), higher lactic acid (3.26 ± 2.04 mmol/L vs. 1.99 ± 1.33 mmol/L, p < 0.001), lower Glasgow Coma Scale (GCS) scores (7.70 ± 4.28 vs. 11.24 ± 4.14, p < 0.001), and higher ICH score (median 3, IQR 2-4 vs. median 1, IQR 0-3, p < 0.001). Higher AGG was associated with an increased likelihood of mechanical ventilation, and in-hospital mortality (74.6% vs. 38.3% and 47.8% vs. 15.0% respectively, p < 0.001). Placements of tracheostomy and gastrostomy were similar between the two groups (13.4% vs. 11.8%, p = 0.69% and 1.5% and 4.6%, p = 0.34 respectively). The higher AGG group had a more common poor discharge outcome to either long-term acute care, skilled nursing facility, and/or hospice (65.7% vs. 42.6%, p < 0.001). Hospital cost and length of hospitalization did not differ significantly. Although AGG was not an independent predictor of poor outcome, multivariate analysis showed it was significantly associated with poor outcome while admission glucose was not (p < 0.001 vs. p = 0.167). CONCLUSION: Elevated AGG was associated with worse GCS and ICH scores on admission, as well as need for mechanical ventilation, in hospital mortality and poor discharge status. Elevated AGG has value in prediction of outcome, but existing understanding is limited.

Older Age Is Not Associated with Worse Outcomes Following Decompressive Hemicraniectomy for Spontaneous Intracerebral Hemorrhage.

BACKGROUND: Decompressive hemicraniectomy (DHC) is commonly offered after large spontaneous intracerebral hemorrhage (ICH) as a life-saving measure. Based on limited available evidence, surgery is sometimes avoided in the elderly. The association between age and outcomes following DHC in spontaneous ICH remains largely understudied. OBJECTIVE: The goal of this study is to investigate the influence of older age on outcomes of patients who undergo DHC for spontaneous ICH. METHODS: In this retrospective cohort study, inpatient data were obtained from the United States Nationwide Inpatient Sample from 2000 to 2011. Using International Classification of Diseases, ninth revision designations, patients with a primary diagnosis of nontraumatic ICH who underwent DHC were identified. The primary outcome of interest was the association of age to inpatient mortality and poor outcome. Subjects were grouped by age: 18-50, 51-60, 61-70, and more than 70 years. Sample characteristics were compared across age groups using χ2 testing, and univariate and multivariate Poisson Regression was performed using a generalized equation to estimate rate ratios for primary and secondary outcomes. RESULTS: One thousand one hundred and forty four patient cases were isolated. Death occurred in an estimated 28.9% and poor outcome in 86.4%. In multivariate Poisson regression models, there was no difference in hospital mortality or poor outcome by age group. Although younger patients were more likely to be diagnosed with herniation, total complication rate was similar between age groups. CONCLUSIONS: Our study results do not provide evidence that age independently predicts in-hospital mortality or poor outcomes. The true influence of age on outcomes is unclear, and further study is needed to determine which factors may be best in selecting candidates for DHC following spontaneous ICH.

Results From DEFUSE 3: Good Collaterals Are Associated With Reduced Ischemic Core Growth but Not Neurologic Outcome

Background and Purpose- The effect of leptomeningeal collaterals for acute ischemic stroke patients with large vessel occlusion in the late window (>6 hours from last known normal) remains unknown. We sought to determine if collateral status on baseline computed tomography angiography impacted neurological outcome, ischemic core growth, and moderated the effect of endovascular thrombectomy in the late window. Methods- This is a prespecified analysis of DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke). We included patients with computed tomography angiography as their baseline imaging and rated collateral status using the validated scales described by Tan and Maas. The primary outcome is functional independence (modified Rankin Scale score of ≤2). Additional outcomes include the full range of the modified Rankin Scale, baseline ischemic core volume, change from baseline in the ischemic core volume at 24 hours, and death at 90 days. Results- Of the 130 patients in our cohort, 33 (25%) had poor collaterals and 97 (75%) had good collaterals. There was no difference in the rate of functional independence with good versus poor collaterals in unadjusted analysis (30% versus 39%; P=0.3) or after adjustment for treatment arm (odds ratio [95% CI], 0.61 [0.26-1.45]). Good collaterals were associated with significantly smaller ischemic core volume and less ischemic core growth. The difference in the treatment effect of endovascular thrombectomy was not significant ( P=0.8). Collateral status also did not affect the rate of stroke-related death (n [%], good versus poor collaterals, 18/97 [19%] versus 8/33 [24%], P=0.5]. Conclusions- In DEFUSE 3 patients, good leptomeningeal collaterals on single phase computed tomography angiography were not predictive of functional independence or death and did not impact the treatment effect of endovascular thrombectomy. These unexpected findings require further study to confirm their validity and to better understand the role of collaterals for stroke patients with anterior circulation large vessel occlusion in the late therapeutic window. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02586415.

Trends in Transient Ischemic Attack Hospitalizations in the United States.

BACKGROUND: Transient ischemic attack (TIA) is a major predictor of subsequent stroke. No study has assessed nation-wide trends in hospitalization for TIA in the United States. METHODS AND RESULTS: Temporal trends in hospitalization for TIA (International Classification of Diseases, Ninth Revision code 435.0-435.9) from 2000 to 2010 were assessed among adults aged ≥25 years using the Nationwide Inpatient Sample. Age-, sex-, and race/ethnic-specific TIA hospitalization rates were calculated using the weighted number of hospitalizations as the numerator and the US population as the denominator. Age-adjusted rates were standardized to the 2000 US Census population. From 2000 to 2010, age-adjusted TIA hospitalization rates decreased from 118 to 83 per 100 000 (overall rate reduction, -29.7%). Age-specific TIA hospitalization rates increased for individuals aged 24 to 44 years (10-11 per 100 000), but decreased for individuals aged 45 to 64 (74 to 65 per 100 000), 65 to 84 (398 to 245 per 100 000), and ≥85 years (900 to 619 per 100 000). Blacks had the highest age-adjusted yearly hospitalization rates, followed by Hispanics and whites (124, 82, and 67 per 100 000 in 2010). Rates slightly increased for blacks, but decreased for Hispanics and whites. Compared to women, age-adjusted TIA hospitalization rates were lower and declined more steeply in men (132 to 89 per 100 000 versus 134 to 97 per 100 000). CONCLUSIONS: Although overall TIA hospitalizations have decreased in the United States, the reduction has been more pronounced among older individuals, men, whites, and Hispanics. These findings highlight the need to target risk-factor control among women, blacks, and individuals aged <45 years.

Trends in Acute Ischemic Stroke Hospitalizations in the United States.

BACKGROUND: Population-based studies have revealed declining acute ischemic stroke (AIS) hospitalization rates in the United States, but no study has assessed recent temporal trends in race/ethnic-, age-, and sex-specific AIS hospitalization rates. METHODS AND RESULTS: Temporal trends in hospitalization for AIS from 2000 to 2010 were assessed among adults ≥25 years using the Nationwide Inpatient Sample. Age-, sex-, and race/ethnic-specific and age-adjusted stroke hospitalization rates were calculated using the weighted number of hospitalizations and US census data. From 2000 to 2010, age-adjusted stroke hospitalization rates decreased from 250 to 204 per 100 000 (overall rate reduction 18.4%). Age-specific AIS hospitalization rates decreased for individuals aged 65 to 84 years (846 to 605 per 100 000) and ≥85 years (2077 to 1618 per 100 000), but increased for individuals aged 25 to 44 years (16 to 23 per 100 000) and 45 to 64 years (149 to 156 per 100 000). Blacks had the highest age-adjusted yearly hospitalization rates, followed by Hispanics and whites (358, 170, and 155 per 100 000 in 2010). Age-adjusted AIS hospitalization rates increased for blacks but decreased for Hispanics and whites. Age-adjusted AIS hospitalization rates were lower in women and declined more steeply compared to men (272 to 212 per 100 000 in women versus 298 to 245 per 100 000 in men). CONCLUSIONS: Although overall stroke hospitalizations declined in the United States, the reduction was more pronounced among older individuals, women, Hispanics, and whites. Renewed efforts at targeting risk factor control among vulnerable individuals may be warranted.

Racial and socioeconomic disparities in incidence of hospital-acquired complications following cerebrovascular procedures.

BACKGROUND: Patients with cerebrovascular disease undergo complex surgical procedures, often requiring prolonged inpatient hospitalization. Previous studies have demonstrated associations between racial/demographic factors and clinical outcomes in patients undergoing cerebrovascular procedures (CVPs). The Centers for Medicare and Medicaid Services have published a series of 11 hospital-acquired conditions (HACs) deemed "reasonably preventable" for which related costs of treatment are not reimbursed. We hypothesize that race and payer status disparities impact HAC frequency in patients undergoing CVPs and that HAC incidence is associated with length of stay and hospital costs. OBJECTIVE: To assess health disparities in HACs among the cerebrovascular neurosurgical patient population. METHODS: Data were collected from the Nationwide Inpatient Sample (NIS) database from 2002 to 2010. CVPs and HACs were identified by International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic and procedure codes. HAC incidence was evaluated according to demographics including race, payer status, and median zip code income via multivariable analysis. Secondary outcomes of interest included length of stay and resulting inpatient charges. RESULTS: From 2002 to 2010, there were 1 290 883 CVP discharges with an HAC rate of 0.5%. Significant disparities in HAC frequency existed according to ethnicity and insurance provider. Minorities and Medicaid patients had increased frequency of HACs (P < .05), as well as prolonged length of stay and higher inpatient costs (P < .05). CONCLUSION: HAC incidence is associated with racial and socioeconomic factors in patients who undergo CVPs. Awareness of these disparities may lead to improved processes and protocol implementation, which might help to decrease the frequency of these potentially avoidable events.

Therapeutic hypothermia in acute ischemic stroke.

Induced hypothermia has been used for neuroprotection in cardiac and neurovascular procedures. Experimental and translational studies provide evidence for its utility in the treatment of ischemic cerebrovascular disease. Over the past decade, these principles have been applied to the clinical management of acute stroke. Varying induction methods, time windows, clinical indications, and adjuvant therapies have been studied. In this article the authors review the mechanisms and techniques for achieving therapeutic hypothermia in the setting of acute stroke, and they outline pertinent side effects and complications. The manuscript summarizes and examines the relevant clinical trials to date. Despite a reasonable amount of existing data, this review suggests that additional trials are warranted to define the optimal time window, temperature regimen, and precise clinical indications for induction of therapeutic hypothermia in the setting of acute stroke.