Conversion From Intravenous Alteplase to Tenecteplase for Treatment of Acute Ischemic Stroke Across a Large Community Hospital Health System.

BACKGROUND: Recent evidence suggests tenecteplase at an intravenous dose of 0.25 mg/kg is as safe and efficacious as intravenous alteplase standard dose and demonstrates a more favorable pharmacokinetic profile for treatment of acute ischemic stroke. OBJECTIVE: The purpose was to compare the safety and efficacy of alteplase versus tenecteplase for the treatment of acute ischemic stroke at a large community hospital health system following conversion in the preferred formulary thrombolytic. METHODS: Prior to converting, medication safety and operationalization analyses were conducted. A multicenter, retrospective medical record review was performed for patients who received alteplase 6 months prior to formulary thrombolytic conversion and for tenecteplase 6 months post-conversion for the treatment of acute ischemic stroke. Primary outcomes included the rate of symptomatic intracranial and extracranial hemorrhage complications. Secondary outcomes included door-to-needle time, reduction in National Institute Health Stroke Scale at 24 hours and at discharge, order-to-administration time, and thrombolytic errors. The rates of hemorrhage were compared using binomial regression. RESULTS: Of the 287 patients reviewed, 115 received alteplase and 172 received tenecteplase. Symptomatic intracranial hemorrhagic complications occurred in 1 patient (1%) who received alteplase compared with 3 patients (2%) who received tenecteplase (P = 0.9). There was no statistical difference in rates of symptomatic intracranial or extracranial hemorrhagic complications. CONCLUSION AND RELEVANCE: Conversion from alteplase to tenecteplase can be safely and effectively achieved at a large community hospital health system with differing levels of stroke certification. There were also additional cost savings and practical advantages including workflow benefits.

Cerebrovascular Events and Hospital Discharge Outcomes Associated With Drug Use: A Retrospective Case-Matched Study.

Introduction Individuals using cocaine, methamphetamines, cannabis, and other mood-altering drugs (MADs) have been reported to have greater stroke risk when compared to individuals who do not use these drugs. Yet, the impact that MAD use has on stroke outcomes has not been adequately explored, with existing research not agreeing on the extent to which the use of these drugs influences stroke outcomes. This study aimed to determine the impact that the use of common MADs has on stroke outcome factors such as length of stay (LOS), discharge modified Rankin Scale (mRS), and discharge disposition. Methods A retrospective case-matched study was conducted with two adult cohorts treated for cerebrovascular accidents: those who use MADs and those who do not use MADs prior to their stroke. Subjects identified for the users of MADs cohort were matched at a 1:1 ratio to those who do not use MADs (control cohort) by age, sex, and stroke type (e.g., hemorrhagic or ischemic). Logistic regression was used to calculate odds ratios for functional outcomes for stroke patients with and without prior MAD use. Results Active users of MADs had an increased overall risk of poor stroke outcome, i.e., increased length of stay, discharge disposition other than to home or to rehabilitation, discharge modified Rankin scale (mRS) 3-6 after controlling for stroke severity from initial National Institutes of Health Stroke Scale (NIHSS) (X2{9}=21.68, p<0.01, Cox adjusted R2=0.31). This finding was driven predominately by increased hospital LOS (p=0.006) among the MAD cohort, whereas discharge mRS 3-6 (p=0.24) and discharge disposition to care facility (p=0.27) and expired (p=0.26) did not vary significantly between groups. Conclusion Our study suggests that patients who had actively used MADs prior to their stroke may be at risk of poorer stroke outcomes, namely an increased LOS. Future research should be conducted to further elucidate which factors, such as individual drugs, amount of drug, acute or recreational use versus chronic or long-term use, and route of administration, for instance, specifically contribute to a longer LOS so that they may be targeted for mitigation.

Comparing Echocardiograms of Haitian and non-Haitian Stroke Patients.

INTRODUCTION: Haitian stroke patients had higher diastolic and mean arterial blood pressures, compared with non-Haitian controls. Therefore, we hypothesized that Haitians would have a higher prevalence of left ventricular hypertrophy and decreased ejection fraction. METHODS: Using the Haitian Stroke Database, a cohort study was conducted. The following transthoracic echocardiographic parameters of 52 Haitians and 111 non-Haitians were compared: left ventricular hypertrophy; ejection fraction; right and left ventricular internal dimension at diastole; and left atrial size. RESULTS: Left ventricular hypertrophy and decreased ejection fraction were more prevalent among Haitians (78% vs. 63%; p=.062 and 21% vs. 13%; p=.173, respectively). Neither reached statistical significance. Left atrial enlargement was significantly more prevalent among non-Haitians (36% vs 15%; p=.007). CONCLUSIONS: Left ventricular hypertrophy and decreased ejection fraction were more prevalent in Haitians, but neither finding reached statistical significance. Larger samples are needed for further understanding of stroke comorbidities in Haitians.

Anticoagulation After Ischemic Stroke or Transient Ischemic Attack (TIA) in the Time of Direct Oral Anticoagulation (DOAC) and Thrombectomy.

Objective To assess anticoagulation (AC) timing and appropriateness in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) due to atrial fibrillation (AF) in a predominantly Hispanic community hospital in the era of direct oral AC (DOAC) and endovascular thrombectomy (EVT). Methods Adult patients presenting with known or new-onset AF and primary diagnosis of AIS/TIA admitted to Baptist Hospital of Miami between January 2018 and January 2019 were included. AC appropriateness was determined on medical history and concordance with American Heart Association AHA/American Stroke Association (ASA) AC guidelines. Median time from AIS/TIA diagnosis to AC initiation was the primary endpoint. AC guideline concordance on admission and at discharge, discordant justification, and AC selection were secondary endpoints. Results The sample included 120 patients. AC initiation was five days (interquartile range (IQR) 2-9) following AIS/TIA. Patients' receiving intravenous (IV) alteplase experienced a 1.4-day delay in AC initiation (x̅=5.44, SE=1.05, p<.05). There was no significant delay for those receiving EVT. A symptomatic hemorrhagic transformation occurred in 3% (n=3) of patients; only one patient was initiated on AC prior to the event. No recurrent AIS/TIAs occurred prior to discharge. Guideline-based AC concordance increased by 14% to 96% from admission to discharge. Apixaban (78%, n=52) was the most prescribed anticoagulant during hospitalization. Discussion This study suggests that early AC initiation for patients with AF and AIS/TIA with or without IV alteplase and/or EVT is a safe and effective stroke prevention intervention. Further, it identified a need for improved concordance with guideline-based AC within the clinic setting.

Risk of contracting SARS-CoV-2 (COVID-19) from hospital admission and the impact of protection efforts on acute stroke treatment.

BACKGROUND: It is unclear how interventions designed to restrict community and in-hospital exposure to the SARS-CoV-2 (COVID-19) virus influenced stroke care for patients seeking acute treatment. Therefore, we aimed to determine how these COVID-19 interventions impacted acute stroke treatment times and to assess the risk of contracting COVID-19 due to their stay in our medical center. METHODS: Retrospective, single center, two-phase study evaluating hospital and community trends from 12/2019 - 04/2020 compared to the previous year and pre/post (n = 156/93) intervention implementation. Phase I assessed stroke treatment times, delay to hospital arrival, and witnessed stroke volume. Phase II, a post-implementation telephone survey, assessed risk of developing symptoms or testing positive for COVID-19. RESULTS: Stroke volume declined by 29% (p < .05) from April to March compared to the previous year. However, no significant delays in seeking medical care (pre Mdn=112, post Mdn=95, p = .34) was observed. Witnessed stroke volume decreased 11% (p < .001) compared to the pre-implementation group, but no significant delay in IV alteplase (pre Mdn=22 mins; post Mdn=26 mins, p = .08) nor endovascular treatment (pre Mdn=60 mins; post Mdn=80 mins, p = .45) was observed. In Phase II, 63 patients participated, two tested (3%) COVID-19 positive during admission and four (6%) within two weeks of discharge. COVID-19 contraction risk during and after hospitalization remained similar to the general population (RR=1.75, 95%CI: 0.79-3.63). Overall results indicated a marked decrease in stroke volume, no significant delays to either seek or provide acute stroke care were evident, and COVID-19 contraction risk was low. CONCLUSIONS: Seeking acute stroke medical care outweighs the risk of COVID-19 exposure.

Maximum intravenous alteplase dose for obese stroke patients is not associated with greater likelihood of worse outcomes.

BACKGROUND: IV alteplase is a primary treatment for acute ischemic stroke (AIS) at a weight-based dose (WBD) of 0.9 mg/kg and maximum dose (MD) of 90 mg. There are conflicting data regarding outcomes for those weighing ≥100 kg. There is also a paucity of data in Hispanics. The prevalence of adult obesity in the US has progressively increased; hence, the percentage of patients receiving the maximum dose also is expected to rise. We examined differences between patients treated with WBD vs. MD. METHODS: A retrospective review of our center's Get With The Guidelines-Stroke database was performed for IV alteplase cases between October 2013-February 2017. Selection criteria included age ≥18 years, IV alteplase administration, and a recorded measured weight. Patients were dichotomized into WBD group weighing <100 kg and MD group weighing ≥100 kg. Categorical variables were analyzed using Chi square tests and continuous variables were analyzed using independent samples t-tests. Multivariable logistic regression analysis was performed to determine whether MD in combination with other variables was associated with poor outcomes. RESULTS: There were 328 patients included in the study, 38 (11.6%) received MD. Proportions of younger, male, and non-Hispanic were higher in the MD group. There were no statistically significant differences for initial NIHSS, discharge modified Rankin Scale (mRS), 90-day mRS, symptomatic intracerebral hemorrhage (sICH), or systemic hemorrhage between groups. CONCLUSION: One in ten patients thrombolysed for the treatment of AIS received MD. In a predominantly Hispanic population, those who received MD and WBD had similar rates of sICH, discharge disposition, and functional outcome (mRS) at discharge and at 90 days. Limitations include small sample size and attrition for the 90-day mRS.

Prenatal light exposure influences gait performance and body composition in bobwhite quail chicks.

Maternal nesting behavior, which includes periods of patterned inattention, provides key elements essential for avian embryonic development, including regulation of temperature and light. For example, avian research consistently shows the importance of prenatal light exposure for several developmental processes; however, this research has primarily focused on artificial light regimens (i.e. 24 hr, 0 hr light). Comparatively less is known about how exposure to naturally occurring light patterns during incubation influence motor performance, body composition (i.e. body mass, bone length), and developmental age (incubation length). Here we conducted two experiments which investigated the effects of prenatal light exposure on developmental age, body composition, and gait performance in 1-day-old bobwhite quail. Experiment 1 investigated crepuscular light exposure during the last two days of incubation under two light duration treatments (2 hr & 6 hr) compared to a 12 hr continuous light schedule. Results indicated crepuscular prenatal light experience extended the incubation period for 2 hr exposed embryos, but not for 6 hr exposed embryos and negatively influenced postnatal body composition and postnatal gait performance when compared to 12 hr continuous light embryos. Experiment 2 examined the influence of prenatal light duration (2 hr vs 6 hr) and light presentation (crepuscular vs sporadic). Results demonstrated sporadic light presentation improved gait performance in 2 hr exposed hatchlings, but not 6 hr exposed hatchlings, improved body composition in 6 hr exposed hatchlings, but not 2 hr exposed hatchlings, and did not alter incubation length when compared to crepuscular light counterparts. This study provides further evidence for the importance of maternally regulated sensory stimulation during the prenatal period on early postnatal motor development.

Prenatal incubation temperature affects neonatal precocial birds' locomotor behavior.

Temperature during the prenatal period is an important factor for developing embryos. Extensive human and animal research indicate embryos are sensitive to small fluctuations in temperature which has profound effects on phenotype development. Much of this research has focused on survivability, morphology, and incubation duration, but comparatively less in known about how prenatal temperature influences the development of motor coordination. In this study, we experimentally tested whether exposure to naturally occurring cool (36.9 °C) or warm (38.1 °C) thermal conditions for a brief period (4 days) during early incubation can influence postnatal motor performance in neonatal bobwhite quail hatchlings. We compared gait spatiotemporal parameters, body kinematics, and locomotive behaviors of control chicks incubated in an optimal thermal environment (37.5 °C) with thermally manipulated chicks. Experimental temperature treatment began on embryonic day five (E5) and ended on E8. Chicks were tested 24-h after hatching. Cool thermal exposure during incubation delayed hatching, reduced body mass, and increased fall frequency, intertarsal joint angle and stride length variability during the gait task compared to optimally incubated chicks. Warm thermal exposure during incubation delayed bone growth and increased fall frequency relative to controls. We discuss the relationship between motor development and thermal regulatory processes and provide insight into how spatiotemporal parameters aid in elucidating subtle differences in coordinated movement which may contribute to atypical motor development and be associated with neural developmental disorders. We provide the first spatiotemporal evidence for the importance of optimal thermal microclimates for typical prenatal motor development.

Coordinated movement is influenced by prenatal light experience in bobwhite quail chicks (Colinus virginianus).

Sensory-motor development begins early during embryogenesis and is influenced by sensory experience. Little is known about the prenatal factors that influence the development of motor coordination. Here we investigated whether and to what extent prenatal light experience can influence the development of motor coordination in bobwhite quail hatchlings. Quail embryos were incubated under four light conditions: no light (dark), 2h of total light (2HR), 6h of total light (6HR), and diffused sunlight (controls). Hatchlings were video recording walking down a runway at three developmental ages (12, 24, and 48h). Videos were assessed for forward locomotion, a measurement of motor coordination, falls, a measurement of motor instability, and motivation to complete the task. We anticipated a linear decline of coordination with a reduction in prenatal light experience and improved coordination with age. Furthermore, as motor coordination becomes more laborious we anticipated motivation to complete the task would decline. However, our findings revealed hatchlings did not uniformly improve with age as expected, nor did the reduction of light result in a linear reduction in motor coordination. Instead, we found a more complex relationship with 6HR and 2HR hatchlings showing distinct patterns of stability and instability. Similarly, we found a reduction in motivation within the 6HR light condition. It appears that prenatal light exposure influences the development of postnatal motor coordination and we discuss these finding in light of neurodevelopmental processes influenced by light experience.

Embraces are lateralized in spider monkeys (Ateles fusciceps rufiventris).

Side biases observed in behavior are thought to reflect underlying asymmetric brain function or hemispheric specialization. Previous work in multiple species identified left side biases (associated with the right hemisphere) for processing social behavior. In highly social species such as primates, many behaviors may be categorized as social, yet differences between such behaviors have not been examined as a test of asymmetric brain function. Using Colombian spider monkeys (Ateles fusciceps rufiventris), we observed lateral positioning during two types of behaviors widely categorized as social affiliative: embracing and grooming, and identified a left bias for embracing, but not grooming. Our findings partially support prior research in hemispheric specialization, but suggest that there may be differences between social behaviors that drive specialization. We discuss these results in light of current theory on hemispheric specialization and highlight differences between embracing and grooming.

Maternal behavior influences development of a reflexive action pattern in the newborn rat.

This study examined the effect of maternal behavior on the expression and postnatal development of a reflexive behavior in rat pups. In neonatal rats, the leg extension response (LER) is a bilateral hyperextension of the hindlimbs in response to maternal anogenital licking (AGL). Past research has found that intranasal application of zinc sulfate (ZnSO4 ) to the dam induces hyponosmia, thereby reducing the incidence of AGL. In this study, pregnant dams received intranasal application of air (control), distilled water (control), or ZnSO4 on the day before birth and every other day thereafter until postnatal day 9 (P9). The LER was experimentally evoked in pups, using a vibrotactile device, at P1, P5, or P10. Pups born to ZnSO4 -treated dams showed significantly shorter bilateral LER durations and significantly smaller ankle angles than pups born to control dams. Reduction of overall maternal AGL approached significance, and afternoon AGL was significantly reduced. These data suggest that maternal behavior influenced development of the LER in rat pups, demonstrating the influence of maternal care on behavioral development during the perinatal period.

Sensorimotor training during expression of the leg extension response (LER) in 1-day-old rats.

In newborn rats, the leg extension response (LER) is a coordinated hyperextension of the hindlimbs that is shown in response to anogenital stimulation. Here we examined the influence of sensorimotor training on LER expression in postnatal day 1 rats. In Experiment 1, we examined if proprioceptive feedback facilitates LER expression. We did this by repeatedly stimulating the pup's anogenital region with a vibrotactile device, to experimentally evoke the LER, thus increasing LER-relevant hindlimb proprioceptive feedback during training. In trained subjects, the LER was evoked every 4 min for 15 trials, followed by a final LER test. Results indicated that proprioceptive feedback on its own did not alter later expression of the LER. In Experiment 2, we examined the effect of both proprioceptive and cutaneous feedback on LER expression, through the use of a range of motion (ROM) restriction during training. During ROM restriction, a Plexiglas plate was placed beneath the pup at 50% of limb length. After the 15th training trial, a final LER test occurred with no ROM restriction in place. Compared to controls, pups that experienced ROM restriction exhibited a significantly shorter LER duration, and smaller hip and ankle angles during the LER test (indicating greater limb flexion). Together these findings show that concurrent proprioceptive and cutaneous feedback, but not proprioceptive feedback alone, has persistent effects on expression of this newborn action pattern.