Effect of Intravenous Tenecteplase Dose on Cerebral Reperfusion Before Thrombectomy in Patients With Large Vessel Occlusion Ischemic Stroke: The EXTEND-IA TNK Part 2 Randomized Clinical Trial.

Importance: Intravenous thrombolysis with tenecteplase improves reperfusion prior to endovascular thrombectomy for ischemic stroke compared with alteplase. Objective: To determine whether 0.40 mg/kg of tenecteplase safely improves reperfusion before endovascular thrombectomy vs 0.25 mg/kg of tenecteplase in patients with large vessel occlusion ischemic stroke. Design, Setting, and Participants: Randomized clinical trial at 27 hospitals in Australia and 1 in New Zealand using open-label treatment and blinded assessment of radiological and clinical outcomes. Patients were enrolled from December 2017 to July 2019 with follow-up until October 2019. Adult patients (N = 300) with ischemic stroke due to occlusion of the intracranial internal carotid, \basilar, or middle cerebral artery were included less than 4.5 hours after symptom onset using standard intravenous thrombolysis eligibility criteria. Interventions: Open-label tenecteplase at 0.40 mg/kg (maximum, 40 mg; n = 150) or 0.25 mg/kg (maximum, 25 mg; n = 150) given as a bolus before endovascular thrombectomy. Main Outcomes and Measures: The primary outcome was reperfusion of greater than 50% of the involved ischemic territory prior to thrombectomy, assessed by consensus of 2 blinded neuroradiologists. Prespecified secondary outcomes were level of disability at day 90 (modified Rankin Scale [mRS] score; range, 0-6); mRS score of 0 to 1 (freedom from disability) or no change from baseline at 90 days; mRS score of 0 to 2 (functional independence) or no change from baseline at 90 days; substantial neurological improvement at 3 days; symptomatic intracranial hemorrhage within 36 hours; and all-cause death. Results: All 300 patients who were randomized (mean age, 72.7 years; 141 [47%] women) completed the trial. The number of participants with greater than 50% reperfusion of the previously occluded vascular territory was 29 of 150 (19.3%) in the 0.40 mg/kg group vs 29 of 150 (19.3%) in the 0.25 mg/kg group (unadjusted risk difference, 0.0% [95% CI, -8.9% to -8.9%]; adjusted risk ratio, 1.03 [95% CI, 0.66-1.61]; P = .89). Among the 6 secondary outcomes, there were no significant differences in any of the 4 functional outcomes between the 0.40 mg/kg and 0.25 mg/kg groups nor in all-cause deaths (26 [17%] vs 22 [15%]; unadjusted risk difference, 2.7% [95% CI, -5.6% to 11.0%]) or symptomatic intracranial hemorrhage (7 [4.7%] vs 2 [1.3%]; unadjusted risk difference, 3.3% [95% CI, -0.5% to 7.2%]). Conclusions and Relevance: Among patients with large vessel occlusion ischemic stroke, a dose of 0.40 mg/kg, compared with 0.25 mg/kg, of tenecteplase did not significantly improve cerebral reperfusion prior to endovascular thrombectomy. The findings suggest that the 0.40-mg/kg dose of tenecteplase does not confer an advantage over the 0.25-mg/kg dose in patients with large vessel occlusion ischemic stroke in whom endovascular thrombectomy is planned. Trial Registration: ClinicalTrials.gov Identifier: NCT03340493.

Health service management study for stroke: a randomized controlled trial to evaluate two models of stroke care.

BACKGROUND: The most effective and efficient model for providing organized stroke care remains uncertain. This study aimed to compare the effect of two models in a randomized controlled trial. METHODS: Patients with acute stroke were randomized on day one of admission to combined, co-located acute/rehabilitation stroke care or traditionally separated acute/rehabilitation stroke care. Outcomes measured at baseline and 90 days postdischarge included functional independence measure, length of hospital stay, and functional independence measure efficiency (change in functional independence measure score ÷ total length of hospital stay). RESULTS: Among 41 patients randomized, 20 were allocated co-located acute/rehabilitation stroke care and 21 traditionally separated acute/rehabilitation stroke care. Baseline measurements showed no significant difference. There was no significant difference in functional independence measure scores between the two groups at discharge and again at 90 days postdischarge (co-located acute/rehabilitation stroke care: 103.6 ± 22.2 vs. traditionally separated acute/rehabilitation stroke care: 99.5 ± 27.7; P = 0.77 at discharge; co-located acute/rehabilitation stroke care: 109.5 ± 21.7 vs. traditionally separated acute/rehabilitation stroke care: 104.4 ± 27.9; P = 0.8875 at 90 days post-discharge). Total length of hospital stay was 5.28 days less in co-located acute/rehabilitation stroke care compared with traditionally separated acute/rehabilitation stroke care (24.15 ± 3.18 vs. 29.42 ± 4.5, P = 0.35). There was significant improvement in functional independence measure efficiency score among participants assigned to co-located acute/rehabilitation stroke care compared with traditionally separated acute/rehabilitation stroke care (co-located acute/rehabilitation stroke care: median 1.60, interquartile range: 0.87-2.81; traditionally separated acute/rehabilitation stroke care: median 0.82, interquartile range: 0.27-1.57, P = 0.0393). Linear regression analysis revealed a high inverse correlation (R(2) = 0.89) between functional independence measure efficiency and time spent in the acute stroke unit. CONCLUSION: This proof-of-concept study has shown that co-located acute/rehabilitation stroke care was just as effective as traditionally separated acute/rehabilitation stroke care as reflected in functional independence measure scores, but significantly more efficient as shown in greater functional independence measure efficiency. Co-located acute/rehabilitation stroke care has potential for significantly improved hospital bed utilization with no patient disadvantage.

Preferences, barriers and facilitators for establishing comprehensive stroke units: a multidisciplinary survey.

OBJECTIVES: To determine the preferences of multidisciplinary stroke clinicians for models of inpatient stroke unit care and perceived barriers to establishing a comprehensive stroke unit (CSU) model (acute and rehabilitation care in the same ward). METHODS: Written questionnaires distributed and completed at multidisciplinary stroke unit case conferences in NSW, Australia. RESULTS: Twenty hospitals with 22 stroke units were surveyed, 13 acute stroke units, 7 rehabilitation stroke units, 2 CSUs. Two hundred and twenty-eight respondents: 99 (43.4%) allied health, 72 (31.6%) nurses and 57 (25.0%) doctors. One hundred and fifty-one respondents (67.0%) thought CSU to be the best model. Seventy-three % of doctors and 79% of allied health preferred CSU v. 57% of nurses (P=0.041). Of doctors, rehabilitation specialists were most likely to favour comprehensive model (84.2%) and neurologists least (57.0%). The main perceived advantages of CSU were reduced cost and improved functional outcomes; perceived disadvantages were increased workload and unwell patients unable to participate in rehabilitation. Main perceived barriers to establishing CSU were lack of space, money, staffing and time. CONCLUSION: Although most current stroke unit care in NSW is based on the traditional model of acute and rehabilitation components in separate wards or hospitals, the majority of multidisciplinary stroke team clinicians believe CSU is the optimum model. What is known about the topic? Stroke unit care is known to improve survival and dependency but the optimum model of care is unproven, despite some small studies suggesting that the CSU model may result in better outcomes. What does this paper add? This paper is the first to survey stroke clinicians from various disciplines and types of unit, to determine their preferences for stroke unit model. What are the implications for practitioners? A majority of clinicians expressed a preference for the CSU model, suggesting that most would be comfortable caring for patients in both acute and rehabilitation phases of stroke care if further such units are established.

Venous thromboembolism in psychogeriatric in-patients--a study of risk assessment, incidence, and current prophylaxis prescribing.

BACKGROUND: While venous thromboembolism (VTE) risk assessment and prophylaxis is well established for medical and surgical in-patients, there is a paucity of evidence, and therefore guidelines, in this area for psychogeriatric in-patients. We wished to determine VTE incidence, risk, and use of prophylaxis, in a psychogeriatric in-patient population. METHODS: Retrospective audit of consecutive psychogeriatric patients aged 65 years and over admitted to Bankstown Hospital over a 3-year period, 2007-2009. Using an adapted VTE risk scoring system, patients were assigned as low, medium, or high VTE risk. RESULTS: A total of 192 patients were included in the study. Mean age was 79.1 ± 7.0 years. Out of the total, 55.2% of patients had diagnosis of dementia, and 33.3% had depression. Overall, 81.8% (157/192) were assessed as low risk, and 18.2% (35/192) as medium risk. Also, 16.7% (32/192) received VTE prophylaxis. Four new VTE events occurred in medium-risk group, and one in low-risk group (p = 0.004). Overall VTE incidence was 10.5/10,000 patient-days, but 44.2 per 10,000 in medium-risk group. VTE risk score was predictive of VTE events - IRR 6.02 (95% Confidence Intervals (CI) = 1.76-20.7, p = 0.004) for every one-point increment in risk. Depression was associated with significantly higher VTE occurrence (6.3% in those with diagnosis vs. 0.8% without, p = 0.043). CONCLUSION: Using a VTE risk scoring system adapted for psychogeriatric in-patients, those assessed to be at medium risk had a significantly increased rate of VTE. On this basis, we would recommend VTE prophylaxis be prescribed for psychogeriatric in-patients assessed to be at medium and high level of risk.

Comprehensive stroke units: a review of comparative evidence and experience.

BACKGROUND: Stroke unit care offers significant benefits in survival and dependency when compared to general medical ward. Most stroke units are either acute or rehabilitation, but comprehensive (combined acute and rehabilitation) model (comprehensive stroke unit) is less common. AIM: To examine different levels of evidence of comprehensive stroke unit compared to other organized inpatient stroke care and share local experience of comprehensive stroke units. METHODS: Cochrane Library and Medline (1980 to December 2010) review of English language articles comparing stroke units to alternative forms of stroke care delivery, different types of stroke unit models, and differences in processes of care within different stroke unit models. Different levels of comparative evidence of comprehensive stroke units to other models of stroke units are collected. RESULTS: There are no randomized controlled trials directly comparing comprehensive stroke units to other stroke unit models (either acute or rehabilitation). Comprehensive stroke units are associated with reduced length of stay and greatest reduction in combined death and dependency in a meta-analysis study when compared to other stroke unit models. Comprehensive stroke units also have better length of stay and functional outcome when compared to acute or rehabilitation stroke unit models in a cross-sectional study, and better length of stay in a 'before-and-after' comparative study. Components of stroke unit care that improve outcome are multifactorial and most probably include early mobilization. A comprehensive stroke unit model has been successfully implemented in metropolitan and rural hospital settings. CONCLUSIONS: Comprehensive stroke units are associated with reductions in length of stay and combined death and dependency and improved functional outcomes compared to other stroke unit models. A comprehensive stroke unit model is worth considering as the preferred model of stroke unit care in the planning and delivery of metropolitan and rural stroke services.

Management and outcomes of delirious patients with hyperactive symptoms in a secured behavioral unit jointly used by geriatricians and pyschogeriatricians.

To compare the clinical outcomes and length of stay (LOS) between delirious patients with hyperactive symptoms admitted directly and those admitted indirectly from Emergency Department into a secured, behavioral unit jointly used by geriatricians and pyschogeriatricians (the Unit). A retrospective study analyzing data from the medical records of 122 patients with an admission diagnosis of delirium with hyperactive symptoms and subsequently discharged from the Unit, including restraint, one-to-one nursing care, falls, absconding, duration of delirium, recovery from delirium, destination and LOS. Significantly fewer patients with direct admission (n=68) required physical restraint or chemical restraint compared with those transferred (n=54). Patients admitted directly showed a higher discharge rate back home, shorter LOS, shorter duration of delirium and a higher rate of recovery from delirium than transferred patients. Of the transferred patients, more received one-to-one nursing care before transfer than after transfer. Three (5.6%) absconded before transfer, but none absconded from the Unit. The falls rate reduced from 14.2 to 6.7 falls/1000 patient delirium days after transfer. Delirious patients with hyperactive symptoms admitted directly to the Unit fared better in clinical outcomes and LOS. They also required less restraint, less intensive nursing and were unlikely to abscond compared to those transferred.

A prospective review of hip fracture subtypes, surgical procedure, cognitive status, and analgesia use across 4 Australian hospitals.

OBJECTIVES: To correlate analgesia use among patients with hip fracture requiring surgery with hip fracture subtype, cognitive status, and type of surgery in the postacute period. DESIGN AND PARTICIPANTS: Prospective review of patients with hip fractures requiring surgical intervention. A total of 415 patients (mean age: 81.2 ± 9.1 years, 74.3% women) presented with 195 subcapital fractures (39 undisplaced, 156 displaced) and 220 trochanteric fractures (136 stable, 84 unstable) requiring surgery. SETTING: Inpatient orthopedic units in 4 Australian hospitals. MEASUREMENTS: The primary outcome measures were mean analgesia usage (oral morphine equivalent) for 4 defined time intervals and total amount 36 hours following surgery. RESULTS: Patients with subtrochanteric fractures required more analgesia compared with displaced-subcapital, undisplaced-subcapital, basicervical, stable-pertrochanteric, and unstable-pertrochanteric fractures in the 24 to 36 hours following operation (24.7 vs 11.3 vs 8.8 vs 12.1 vs 7.6 vs 9.7, P = .001). Total analgesia requirements were higher in patients treated with an intramedullary nail, increasing by 1.3- to 3.3-fold in the 36 hours postsurgery. Patients with cognitive impairment utilized markedly less analgesia at all time periods measured. At 24 to 36 hours, higher levels of analgesia were noted in patients with higher premorbid level of mobility (P = .015) and activities of daily living function (P = .007). CONCLUSION: Important differences in utilization of analgesia following hip fracture across readily defined clinical groups exist. Proactive pain management for those with cognitive impairment, certain hip fracture subtypes, and surgical procedures may enable early functional mobility and other activities.

Dysphagia: causes, assessment, treatment, and management.

Dysphagia, or difficulty in swallowing, is a condition with a strong age-related bias. Rates of dysphagia vary due to differences in method between studies; eg, clinical history of "swallowing difficulty," evidence of aspiration, or dysphagia confirmed by swallowing investigations. In general, the rate is lower in the community than in nursing home facilities. The management and treatment of dysphagia among geriatric patients is complicated by cognitive decline, lowered immunity, malnutrition, and end-of-life decisions. This article reviews the current assessment, treatment, and management techniques for dysphagia; covers new developments in research and pilot studies; and reviews the ethical issues related to treatment when prognosis is poor.

Management for motor and non-motor complications in late Parkinson's disease.

The prevalence of neurodegenerative diseases such as Parkinson's disease (PD) increases with age. In an aging population, an understanding of the management of late complications of PD is becoming ever more important. Drug treatment for Parkinson's disease is largely symptomatic and relies primarily on levodopa (L-dopa) and adjuvant therapies including dopamine agonists and catechol-O-methyltransferase (COMT) inhibitors. Rehabilitation and allied health input also constitutes a core part of successful management. Most subjects who are symptomatic for more than 5 years are prone to late complications of PD. Some of these are related to the treatment, such as motor fluctuations, including the "on-off" phenomenon and levodopa-related peak dose dyskinesia. Others, such as postural hypotension, falls, psychosis, and dementia, although well-recognized problems in the elderly, often require different treatment strategies if occurring in the context of PD. The practical evidence-based management of motor and non-motor complications in late PD is discussed.

Localised herpes zoster infection and SIADH.

Localised herpes zoster infection ('shingles') in older patients is a common presentation to primary, and sometimes secondary, care physicians. However, symptoms of hyponatraemia, caused by the rare complication of 'syndrome of inappropriate antidiuretic hormone secretion' (SIADH), may be mistaken for constitutional symptoms of the infection itself. Such patients may require closer monitoring or hospitalisation.

Endothelial progenitor cells during cerebrovascular disease.

BACKGROUND AND PURPOSE: Endothelial progenitor cells (EPCs) are associated with endothelial repair after ischemia in cardiac or peripheral circulation. There are no reports of EPCs with cerebrovascular disease. We present our experience with EPCs in patients with cerebrovascular disease. SUMMARY OF REPORT: EPC counts differed significantly (P<0.001) between stroke patients (acute stroke: median 4.75 and range 0 to 33; stable stroke: median 7.25 and range 0 to 43) and control subjects (median 15.5 and range 4.3 to 50), independent of age. The level of EPCs was significantly correlated with the Framingham coronary risk score (FCRS) (rho=-0.349; P=0.002). CONCLUSIONS: Similar to cardiac experience, the low EPC levels may play a role in the pathophysiology of cerebrovascular disease.

Current and future concepts in stroke prevention.

Stroke is a major cause of morbidity and mortality in an aging population. The current understanding of the pathophysiology of atherosclerotic diseases, the most common cause of stroke, and the evidence for existing therapeutic interventions for the prevention of stroke are presented. Specifically, we review the evidence for antiplatelet agents, anticoagulants, antihypertensive medications, lipid-lowering agents and carotid endarterectomy for stroke prevention.

Atrial myxoma as a cause of stroke: case report and discussion.

Cardiac myxoma is a source of emboli to the central nervous system and elsewhere in the vascular tree. However, nonspecific systemic symptoms and minor embolic phenomena may be overlooked in the absence of any history of cardiac problems. In this situation, cardiac investigations may not be performed, and diagnosis of this rare condition may be delayed until the onset of more significant embolic disease, such as stroke with functional impairment, as in the case reported here. The clinical presentation of cardiac myxoma is discussed, along with appropriate investigations and treatment, which may prevent such sequelae.