Adjunctive Intravenous Argatroban or Eptifibatide for Ischemic Stroke.

BACKGROUND: Intravenous thrombolysis is a standard treatment of acute ischemic stroke. The efficacy and safety of combining intravenous thrombolysis with argatroban (an anticoagulant agent) or eptifibatide (an antiplatelet agent) are unclear. METHODS: We conducted a phase 3, three-group, adaptive, single-blind, randomized, controlled clinical trial at 57 sites in the United States. Patients with acute ischemic stroke who had received intravenous thrombolysis within 3 hours after symptom onset were assigned to receive intravenous argatroban, eptifibatide, or placebo within 75 minutes after the initiation of thrombolysis. The primary efficacy outcome, the utility-weighted 90-day modified Rankin scale score (range, 0 to 10, with higher scores reflecting better outcomes), was assessed by means of centralized adjudication. The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours after randomization. RESULTS: A total of 514 patients were assigned to receive argatroban (59 patients), eptifibatide (227 patients), or placebo (228 patients). All the patients received intravenous thrombolysis (70% received alteplase, and 30% received tenecteplase), and 225 patients (44%) underwent endovascular thrombectomy. At 90 days, the mean (±SD) utility-weighted modified Rankin scale scores were 5.2±3.7 with argatroban, 6.3±3.2 with eptifibatide, and 6.8±3.0 with placebo. The posterior probability that argatroban was better than placebo was 0.002 (posterior mean difference in utility-weighted modified Rankin scale score, -1.51±0.51) and that eptifibatide was better than placebo was 0.041 (posterior mean difference, -0.50±0.29). The incidence of symptomatic intracranial hemorrhage was similar in the three groups (4% with argatroban, 3% with eptifibatide, and 2% with placebo). Mortality at 90 days was higher in the argatroban group (24%) and the eptifibatide group (12%) than in the placebo group (8%). CONCLUSIONS: In patients with acute ischemic stroke treated with intravenous thrombolysis within 3 hours after symptom onset, adjunctive treatment with intravenous argatroban or eptifibatide did not reduce poststroke disability and was associated with increased mortality. (Funded by the National Institute of Neurological Disorders and Stroke; MOST ClinicalTrials.gov number, NCT03735979.).

Telehealth Trials to Address Health Equity in Stroke Survivors.

Telehealth has seen rapid expansion into chronic care management in the past 3 years because of the COVID-19 pandemic. Telehealth for acute care management has expanded access to equitable stroke care to many patients over the past two decades, but there is limited evidence for its benefit for addressing disparities in the chronic care of patients living with stroke. In this review, we discuss advantages and disadvantages of telehealth use for the outpatient management of stroke survivors. Further, we explore opportunities and potential barriers for telehealth in addressing disparities in stroke outcomes related to various social determinants of health. We discuss two ongoing large randomized trials that are utilizing telehealth and telemonitoring for management of blood pressure in diverse patient populations. Finally, we discuss strategies to address barriers to telehealth use in patients with stroke and in populations with adverse social determinants of health.

Adapting Clinical Practice of Thrombolysis for Acute Ischemic Stroke Beyond 4.5 Hours: A Review of the Literature.

Several clinical trials have demonstrated that advanced neuroimaging can select patients for recanalization therapy in an extended time window. The favorable functional outcomes and safety profile of these studies have led to the incorporation of neuroimaging in endovascular treatment guidelines, and most recently, also extended to decision making on thrombolysis. Two randomized clinical trials have demonstrated that patients who are not amenable to endovascular thrombectomy within 4.5 hours from symptoms discovery or beyond 4.5 hours from the last-known-well time may also be safely treated with intravenous thrombolysis and have a clinical benefit above the risk of safety concerns. With the growing aging population, increased stroke incidence in the young, and the impact of evolving medical practice, healthcare and stroke systems of care need to adapt continuously to provide evidence-based care efficiently. Therefore, understanding and incorporating appropriate screening strategies is critical for the prompt recognition of potentially eligible patients for extended-window intravenous thrombolysis. Here we review the clinical trial evidence for thrombolysis for acute ischemic stroke in the extended time window and provide a review of new enrolling clinical trials that include thrombolysis intervention beyond the 4.5 hour window.

A Stroke Care Model at an Academic, Comprehensive Stroke Center During the 2020 COVID-19 Pandemic.

BACKGROUND AND PURPOSE: The COVID-19 pandemic has required the adaptation of hyperacute stroke care (including stroke code pathways) and hospital stroke management. There remains a need to provide rapid and comprehensive assessment to acute stroke patients while reducing the risk of COVID-19 exposure, protecting healthcare providers, and preserving personal protective equipment (PPE) supplies. While the COVID infection is typically not a primary cerebrovascular condition, the downstream effects of this pandemic force adjustments to stroke care pathways to maintain optimal stroke patient outcomes. METHODS: The University of California San Diego (UCSD) Health System encompasses two academic, Comprehensive Stroke Centers (CSCs). The UCSD Stroke Center reviewed the national COVID-19 crisis and implications on stroke care. All current resources for stroke care were identified and adapted to include COVID-19 screening. The adjusted model focused on comprehensive and rapid acute stroke treatment, reduction of exposure to the healthcare team, and preservation of PPE. AIMS: The adjusted pathways implement telestroke assessments as a specific option for all inpatient and outpatient encounters and accounts for when telemedicine systems are not available or functional. COVID screening is done on all stroke patients. We outline a model of hyperacute stroke evaluation in an adapted stroke code protocol and novel methods of stroke patient management. CONCLUSIONS: The overall goal of the model is to preserve patient access and outcomes while decreasing potential COVID-19 exposure to patients and healthcare providers. This model also serves to reduce the use of vital PPE. It is critical that stroke providers share best practices via academic and vetted social media platforms for rapid dissemination of tools and care models during the COVID-19 crisis.

Thrombolysis Following Heparin Reversal With Protamine Sulfate in Acute Ischemic Stroke: Case Series and Literature Review.

INTRODUCTION: Administering intravenous IV tissue plasminogen activator (tPA) is the recommended standard of care in acute ischemic stroke (AIS), although it is not recommended to administer intravenous thrombolysis with tPA following heparin reversal with protamine sulfate in patients with AIS. METHODS: We describe a case series of three patients and the most comprehensive literature review published to date in this specific subset of AIS patients undergoing thrombolysis following heparin reversal with protamine sulfate. The literature review was based on a scoping review methodology performed on four databases; PubMed, CINAHL, Web of Science, and Cochrane Library. All sources were searched from the inauguration of the database until February 2019. A total of six articles involving eight patients were identified. RESULTS: The primary safety outcome of no symptomatic intracranial hemorrhage (sICH) was met in all eleven patients, although only seven cases had a good functional outcome at 3 months. CONCLUSIONS: In appropriately selected AIS patients, coagulopathy correction appears to be safe from an sICH standpoint and may be beneficial. However, given the potential for bias with observational databases, case reports and case series, extreme caution is warranted in applying these results to routine clinical practice.

Personalised stroke evaluation and management: tailoring individualised patient care for hereditary haemorrhagic telangiectasia.

SummaryHereditary haemorrhagic telangiectasia (HHT) has an estimated prevalence of 1 in 5000-8000 individuals globally with pulmonary arteriovenous malformations (PAVMs) affecting approximately 15%-50% of HHT patients. Ischaemic stroke is a known complication of PAVMs that affects ≤30% of patients with PAVMs. Studies have shown that patients with PAVMs have ischaemic stroke a decade earlier than routine stroke. The predominant mechanism of ischaemic stroke in HHT patients is paradoxical embolism due to PAVMs, but most HHT-related PAVMs are asymptomatic. Additionally, HHT is often underdiagnosed in patients and poses a challenge to physicians due to its rarity. We present a case of a patient with ischaemic stroke who was subsequently diagnosed with HHT and found to have a PAVM on further evaluation. This case highlights the importance of using an individualised patient-centred stroke evaluation and screening for PAVMs in patients who had a stroke with possible or suspected HHT and definite HHT.

Bladder carcinoma in situ (CIS) in Australia: a rising incidence for an under-reported malignancy.

OBJECTIVES: To investigate the incidence of carcinoma in situ (CIS) in Australia and examine implications for its diagnosis and management, as CIS of the urinary bladder is a non-reportable disease in Australia. METHODS: Analysis of annual hospitalisation data using Australian Institute of Health and Welfare (AIHW) datasets showed an increase in CIS from 2001 onwards. To determine whether the increase seen with AIHW data represented a true increase in the rates offices, patient level data was examined using the Centre for Health record linkage (CHeReL) datasets. RESULTS: CHeReL linked data of 13,790 males and 5902 females, calculated the average incidence of CIS to be 20.9 per 100,000 and 6.5 per 100,000 respectively in those aged > 50 years, showing a rapid increase in the rates of CIS from 2001. There was an 11% (P = 0.04) and 14% (P = 0.02) annual increase in incidence of CIS in men and women and these rates increased with age. CONCLUSIONS: National data (AIHW) substantially underestimate the incidence of CIS in the Australian population. Patient level data suggest CIS rates are rapidly increasing in Australia despite high treatment rates. Closer surveillance and awareness of these high rates warrants further study and we recommend that CIS be considered a reportable disease.

Are Ischemic Strokes the Same? The Special Case Argument of Atrial Fibrillation.

A comprehensive evaluation is necessary to identify the etiologic factors in order to select optimal stroke-prevention measures. Atrial fibrillation is one of the most important stroke causes. Although anticoagulant therapy is the treatment of choice for patients with nonvalvular atrial fibrillation, it should not be considered uniformly to treat all patients given the high mortality associated with anticoagulant-related hemorrhages. The authors propose a risk-stratified individualized approach for stroke prevention in patients with nonvalvular atrial fibrillation by considering nonpharmacologic approaches for patients at high hemorrhage risk or otherwise unsuitable for lifelong anticoagulation.

Incidence of Atrial Fibrillation in Large Vessel Occlusion and Large Embolic Stroke of Undetermined Source.

INTRODUCTION: Large vessel occlusion (LVO) stroke is a common presentation of acute ischemic stroke and is often unknown or cryptogenic in etiology. There is a strong association between atrial fibrillation (AF) and cryptogenic LVO stroke, making it a unique stroke subgroup. Therefore, we propose that any LVO stroke meeting the criteria for an embolic stroke of an undetermined source (ESUS) be classified as large ESUS (LESUS). The purpose of this retrospective cohort study was to report the etiology of anterior LVO strokes that underwent endovascular thrombectomy. METHODS: This was a single-center retrospective cohort study characterizing the etiology of acute anterior circulation LVO strokes that received emergent endovascular thrombectomy from 2011 to 2018. Patients with LESUS designation at hospital discharge were changed to cardioembolic etiology if AF was discovered during the two-year follow-up period.  Results: Overall, 155 (45%) of 307 patients in the study were found to have AF. New onset AF was discovered in 12 (23%) of 53 LESUS patients after hospitalization. Furthermore, eight (35%) of 23 LESUS patients who received extended cardiac monitoring were found to have AF. CONCLUSION: Nearly half the patients with LVO stroke who received endovascular thrombectomy were found to have AF. With the use of extended cardiac monitoring devices after hospitalization, AF is frequently discovered in patients with LESUS and may change the secondary stroke prevention strategy.

Are Ischemic Strokes the Same? The Special Case Argument of Atrial Fibrillation.

A comprehensive evaluation is necessary to identify the etiologic factors in order to select optimal stroke-prevention measures. Atrial fibrillation is one of the most important stroke causes. Although anticoagulant therapy is the treatment of choice for patients with nonvalvular atrial fibrillation, it should not be considered uniformly to treat all patients given the high mortality associated with anticoagulant-related hemorrhages. The authors propose a risk-stratified individualized approach for stroke prevention in patients with nonvalvular atrial fibrillation by considering nonpharmacologic approaches for patients at high hemorrhage risk or otherwise unsuitable for lifelong anticoagulation.

Incidence of prostate cancer in Sri Lanka using cancer registry data and comparisons with the incidence in South Asian men in England.

OBJECTIVE: •To investigate the incidence of carcinoma of the prostate (CaP) in Sri Lanka and compare the rates with the migrant population in the UK. METHODS: •The Sri Lanka cancer registry data were used to determine the rates of CaP in Sri Lanka from 2001 to 2005. •The incidence of CaP in 8,426,000 men, aged ≥30 years, was analysed using 5-year age bands and age-standardized rates were calculated using European standard population data. •The relative risk was calculated by comparison with the South Asian migrant population in the UK using the Prostate Cancer in Ethnic Subgroups (PROCESS) study data, a population-based retrospective cohort study of 2140 men carried out over a 5-year period in four predefined areas of southern England. •Data from incidental findings of CaP in Sri Lanka on transurethral resection of the prostate (TURP) specimens were also analysed. RESULTS: •In all, 1378 new cases of CaP were diagnosed during the 5-year period with a mean age of 69.2 years at diagnosis. •Compared with the previous 5 years, the incidence of CaP had doubled to 5.7 per 100,000, but was significantly lower than in the PROCESS study (relative risk 0.25). •Districts with a higher population density had higher adjusted rates of CaP in Sri Lanka (5.8-12.4 per 100,000). •For TURP specimens, 16.8-18.75% had incidental diagnoses of CaP in Sri Lanka, higher than other published studies. CONCLUSIONS: •The Sri Lankan cancer registry data showed a low rate of CaP, similar to other South Asian countries, but the actual incidence of CaP in Sri Lanka is probably higher than reported, as seen in the densely populated districts and the high rate of incidental diagnosis of CaP in TURP specimens. •The incidence of CaP in migrant South Asians in the UK was much higher than in Sri Lanka. •Further studies are required to examine the environmental and genetic components which may be responsible for the low incidence of CaP in Sri Lanka.

Acute Onset of Hypersomnolence and Aphasia Secondary to an Artery of Percheron Infarct and a Proposed Emergency Room Evaluation.

Artery of Percheron (AOP) is a rare anatomical variant, which supplies bilateral paramedian thalami and the rostral mesencephalon via a single dominant thalamic perforating artery arising from the P1 segment of a posterior cerebral artery. AOP infarcts can present with a plethora of neurological symptoms: altered mental status, memory impairment, hypersomnolence, coma, aphasia, and vertical gaze palsy. Given the lack of classic stroke signs, majority of AOP infarcts are not diagnosed in the emergency setting. Timely diagnosis of an acute bilateral thalamic infarct can be challenging, and this case report highlights the uncommon neurological presentation of AOP infarction. The therapeutic time window to administer IV tPA can be missed due to this delay in diagnosis, resulting in poor clinical outcomes. To initiate appropriate acute ischemic stroke management, we propose a comprehensive radiological evaluation in the emergency room for patients with a high suspicion of an AOP infarction.

Rare Phenomenon of Limb-shaking TIA, Resolved With Intracranial Wingspan Stenting.

OBJECTIVE: Illustrates the importance of differentiating limb-shaking transient ischemic attack (LS-TIA) from focal seizures and carefully selecting patients for intracranial stenting. BACKGROUND: LS-TIA is associated with severe carotid stenosis or occlusion, often precipitated by cerebral hypoperfusion. A case study of 313 patients with symptomatic intracranial artery stenosis/occlusion reported 11% with LS-TIA. In our literature search, we did not find any other cases of successful treatment of LS-TIA with an intracranial Wingspan stent. DESIGN/METHODS: A 66-year-old woman with a history of atrial fibrillation on anticoagulation, hypertension, hyperlipidemia and left middle cerebral artery (MCA) stroke followed by a left internal carotid artery (ICA) endarterectomy presented with transient repetitive involuntary movements (TRIMs) over her right upper and lower limbs. She described episodes of numbness followed by TRIMs over the right side of her body lasting for 1 to 2 minutes. TRIMs occurred only while standing and usually resolved on sitting or lying down. RESULTS: Conventional angiogram showed severe stenosis of left supraclinoid ICA and proximal MCA. Brain single photon emission computed tomography scan showed impaired vascular reserve in the left MCA territory. An ambulatory electroencephalogram captured TRIMs without epileptiform discharges. She continued to have symptoms with no improvement over a period of 3 months on maximal medical management. She underwent successful endovascular treatment with the Wingspan stent system in the left M1 segment and terminal ICA. Following the revascularization procedure, her symptoms resolved. CONCLUSIONS: It is vitally important to differentiate LS-TIA from focal seizures. This is the first documented case report of complete resolution of LS-TIA symptoms following an intracranial Wingspan stenting.

Trends in penile cancer: a comparative study between Australia, England and Wales, and the US.

PURPOSE: To investigate and compare the trends in incidence and mortality of penile cancer between Australia, England and Wales, and the US, and provide hypotheses for these trends. METHODS: Cancer registry data from 1982 to 2005 inclusive were obtained from Australia, England and Wales, and the United States. From these data, age-specific, -standardised and mortality:incidence ratios were calculated, and compared. RESULTS: The overall incidence of penile cancer in England and Wales (1.44 per 100,000 man-years) was higher than in Australia (0.80 per 100,000), and the US (0.66 per 100,000). Incidence of penile cancer in all three countries has remained relatively stable over time. Similarly, although the mortality rates were also higher in England and Wales (0.37 per 100,000 man-years) compared to Australia (0.18 per 100,000) and the US (0.15 per 100,000), the mortality/incidence ratios were similar for all three countries. CONCLUSIONS: Penile cancer incidence is low, affecting mainly older men. Rates differ between the three countries, being twice as common in England and Wales as in the other studied regions. Circumcision rates have a potential influence on these rates but are not the sole explanation for the variation.

Vitamin D's potential to reduce the risk of hospital-acquired infections.

Health care-associated and hospital-acquired infections are two entities associated with increased morbidity and mortality. They are highly costly and constitute a great burden to the health care system. Vitamin D deficiency (< 20 ng/ml) is prevalent and may be a key contributor to both acute and chronic ill health. Vitamin D deficiency is associated with decreased innate immunity and increased risk for infections. Vitamin D can positively influence a wide variety of microbial infections. Herein we discuss hospital-acquired infections, such as pneumonia, bacteremias, urinary tract and surgical site infections, and the potential role vitamin D may play in ameliorating them. We also discuss how vitamin D might positively influence these infections and help contain health care costs. Pending further studies, we think it is prudent to check vitamin D status at hospital admission and to take immediate steps to address existing insufficient 25-hydroxyvitamin D levels.

Incidence of bladder cancer in sri lanka: analysis of the cancer registry data and review of the incidence of bladder cancer in the South asian population.

PURPOSE: To investigate the incidence of bladder cancer (BC) in Sri Lanka and to compare risk factors and outcomes with those of other South Asian nations and South Asian migrants to the United Kingdom (UK) and the United States (US). MATERIALS AND METHODS: The incidence of BC in Sri Lanka was examined by using two separate cancer registry databases over a 5-year period. Smoking rates were compiled by using a population-based survey from 2001 to 2009 and the relative risk was calculated by using published data. RESULTS: A total of 637 new cases of BC were diagnosed over the 5-year period. Sri Lankan BC incidence increased from 1985 but remained low (1.36 and 0.3 per 100,000 in males and females) and was similar to the incidence in other South Asian countries. The incidence was lower, however, than in migrant populations in the US and the UK. In densely populated districts of Sri Lanka, these rates almost doubled. Urothelial carcinoma accounted for 72%. The prevalence of male smokers in Sri Lanka was 39%, whereas Pakistan had higher smoking rates with a 6-fold increase in BC. CONCLUSIONS: Sri Lankan BC incidence was low, similar to other South Asian countries (apart from Pakistan), but the actual incidence is likely higher than the cancer registry rates. Smoking is likely to be the main risk factor for BC. Possible under-reporting in rural areas could account for the low rates of BC in Sri Lanka. Any genetic or environmental protective effects of BC in South Asians seem to be lost on migration to the UK or the US and with higher levels of smoking, as seen in Pakistan.