The 2008 William M. Feinberg lecture: prioritizing stroke research

Stroke is a tremendous burden to health worldwide both in the developed and developing world. Current levels of research funding do not adequately reflect this burden, particularly when expected increases in stroke rates are considered. Of course, an investment in stroke research is only justified if a return can be expected. The ultimate goal of stroke research is to reduce the burden of disease, and clinical trials are the clearest expression of the value of research because their results can directly impact health. In a review of stroke trials funded by the US National Institute of Neurological Disorders and Stroke, we found that the overall impact of the trials was dramatically positive and justified the entire research budget of the Institute. Nonetheless, there were obvious opportunities for improvement. METHODS: meta--research--on topics not just relevant to stroke, but to the study of all disease.     

William Feinberg lecture 2002: emotions,mood, and behavior after stroke

While emotional outcome is a critical factor influencing early evolution and late prognosis after stroke, few relevant studies have been performed on this subject. However, mood changes, modified judgment, and emotional reactions may also dramatically alter recruitment into clinical trials; for instance, up to one third of patients with acute stroke may have altered time perception, inappropriate self-evaluation of their condition, and attentional or memory dysfunction, with a subsequent increase in referral-to-hospital delays. In addition, the value of the "informed" consenting process may be questionable in the setting of urgent randomization into an acute stroke clinical trial. Data from ongoing studies suggest that behavior and emotional reactions in acute stroke patients may be classified into a few broad categories, with considerable overlap. Correlations between mood changes and the type, location, and severity of stroke may provide useful information for improving patient management, including the prediction of functional evolution and late prognosis. While depressive reactions have been widely studied in the recovery-rehabilitation phase after stroke, significant depression is uncommon shortly after stroke. On the other hand, related, though different, emotional behavioral changes may be more frequent; these have often been confused with depression and include catastrophic reaction, emotionalism, and athymhormia. Late depression is the most common mood alteration during the first year after stroke and has specific characteristics that differentiate it from classic endogenous and reactive depression, thus emphasizing the critical role of brain damage in the pathogenesis of poststroke depression. Early recognition and management of mood disorders after stroke are critical for the functional improvement of individual patients. However, little is known about specific indications for different antidepressant drugs in poststroke depression and related disorders. Ongoing research has identified a "new" emotional-behavioral disorder, poststroke fatigue, which is clearly distinct from depression in most instances. It is especially disabling and frustrating in that it typically involves patients with total or near-total neurological recovery, who should have been able to go back to their previous activities but who become severely disabled because of early and persisting exhaustion. Preliminary neuropsychological and MR and PET imaging studies suggest that disruption of subtle mechanisms underlying attention, in the absence of significant cognitive and mood alterations, may be responsible. Research projects are now being launched to better delineate poststroke fatigue and its management.     

The 2006 William Feinberg lecture: shifting the paradigm from stroke to global vascular risk estimation

By the year 2010, it is estimated that 18.1 million people worldwide will die annually because of cardiovascular diseases and stroke. "Global vascular risk" more broadly includes the multiple overlapping disease silos of stroke, myocardial infarction, peripheral arterial disease, and vascular death. Estimation of global vascular risk requires consideration of a variety of variables including demographics, environmental behaviors, and risk factors. Data from multiple studies suggest continuous linear relationships between the physiological vascular risk modulators of blood pressure, lipids, and blood glucose rather than treating these conditions as categorical risk factors. Constellations of risk factors may be more relevant than individual categorical components. Exciting work with novel risk factors may also have predictive value in estimates of global vascular risk. Advances in imaging have led to the measurement of subclinical conditions such as carotid intima-media thickness and subclinical brain conditions such as white matter hyperintensities and silent infarcts. These subclinical measurements may be intermediate stages in the transition from asymptomatic to symptomatic vascular events, appear to be associated with the fundamental vascular risk factors, and represent opportunities to more precisely quantitate disease progression. The expansion of studies in molecular epidemiology and detection of genetic markers underlying vascular risks also promises to extend our precision of global vascular risk estimation. Global vascular risk estimation will require quantitative methods that bundle these multi-dimensional data into more precise estimates of future risk. The power of genetic information coupled with data on demographics, risk-inducing behaviors, vascular risk modulators, biomarkers, and measures of subclinical conditions should provide the most realistic approximation of an individual's future global vascular risk. The ultimate public health benefit, however, will depend on not only identification of global vascular risk but also the realization that we can modify this risk and prove the prediction models wrong.     

Overcoming barriers to reducing the burden of affective disorders.

Affective disorders impose a substantial individual and societal burden. Despite availability of efficacious treatments and practice guidelines, unmet need remains high. To reduce unmet need and the burden of affective disorders, information is needed on the distribution of burden across stakeholders, on barriers to reducing burden, and on interventions that effectively reduce burden at the levels of practice, community, and policy. This article provides the report of the Working Group on Overcoming Barriers to Reducing the Burden of Affective Disorders, for the National Institute of Mental Health Strategic Plan on Mood Disorders. We review the literature, identify key gaps, and recommend new research to guide national efforts to reduce the burden of affective disorders.     

Epilepsy in Asia: Disease burden,management barriers,and challenges

This article reviews the burden of epilepsy in Asia, the challenges faced by people with epilepsy, and the management of epilepsy. Comparison is made with other parts of the world. For this narrative review, data were collected using specified search criteria. Articles investigating the epidemiology of epilepsy, diagnosis, comorbidities and associated mortality, stigmatization, and treatment were included. Epilepsy is a global health care issue affecting up to 70 million people worldwide. Nearly 80% of people with epilepsy live in low‐ and middle‐income countries with limited resources. People with epilepsy are prone to physical and psychological comorbidities, including anxiety and depression, which can negatively impact their quality of life. Furthermore, people with epilepsy are at higher risk of premature death than people without epilepsy. Discrimination or stigmatization of people with epilepsy is common in Asia and can affect their education, work, and marriage opportunities. Access to epilepsy treatment varies throughout Asia. Although highly advanced treatment is available in some countries, up to 90% of people with epilepsy are not adequately treated or are not treated with conventional antiepileptic therapy in resource‐limited countries. People in remote areas often do not receive any epilepsy care. First‐generation antiepileptic drugs (AEDs) are available, but usually only in urban areas, and second‐generation AEDs are not available in all countries. Newer AEDs tend to have more favorable safety profiles than first‐generation AEDs and provide options to tailor therapy for individual patients, especially those with comorbidities. Active epilepsy surgery centers are present in some countries, although epilepsy surgery is often underutilized given the number of patients who could benefit. Further epidemiologic research is needed to provide accurate epilepsy data across the Asian region. Coordinated action is warranted to improve access to treatment and care.     

轻型缺血性卒中治疗的研究进展

轻型缺血性卒中具有高发病率、高复发率的特点.目前,对于其定义和治疗策略尚存在争议,不合理的治疗方案可能会导致病情进展,从而造成患者致残率和死亡率的增加.现对轻型缺血卒中的定义、治疗策略的研究现状进行综述,旨在为临床实践提供更规范、合理、个体化的轻型缺血性卒中治疗方案.     

Thrombolytic stroke therapy: past, present, and future.

Until 1995, treatment of strokes consisted exclusively of efforts to prevent recurrence. Proof that tissue plasminogen activator is useful for acute management is changing the approach to stroke patients. The development process has been difficult and the current treatment recommendations have been controversial. Recent successful clinical trials lend additional credence to these concepts. Future treatment strategies will probably include combinations of thrombolytics and neuroprotectants of various types. However, the need to initiate treatment rapidly after stroke onset is likely to continue.     

Symptom experience and symptom burden of patients following first-ever stroke within 1 year: a cross-sectional study

Symptoms that are multidimensional and concurrent should be assessed from different dimensions and managed together. Few studies have evaluated concurrent and multidimensional symptoms in patients with stroke. Most studies of stroke focused on dysfunctions and complications. We hypothesize that patients with stroke have a heavy symptom burden within 1 year. This study aimed to describe multidimensional and concurrent symptoms within 1 year after stroke. This study recruited 230 patients with stroke from the Rehabilitation Department of Xuhui District Center Hospital of Shanghai and the Shanghai Sunshine Rehabilitation Center in China from March to September 2017. The patients' multidimensional symptom experience and symptom burden were analyzed using a self-made structured questionnaire and the influential factors for symptom burden were identified. The mean number of symptoms in patients with stroke was 11.7 ± 3.5. More than two thirds of the participants suffered from at least 10 co-occurring symptoms. Unilateral limb weakness had the highest prevalence and frequency. Participation restriction had the highest symptom dimensions of severity and distress. Lack of self-care ability(severity), memory deterioration(frequency), imbalance of body(distress), moodiness(distress), being unable to move limbs at will(distress), shoulder pain(distress), and slower response(frequency) were independent factors of the total symptom burden score. These findings can provide essential information for efficient symptom management of patients with stroke.     

Enhanced physical therapy for arm function after stroke: a one year follow up study.

Ninety seven patients with stroke who had participated in a randomised trial of conventional physical therapy nu an enhanced therapy for arm function were followed up at one year. Despite the emphasis of the enhanced therapy approach on continued use of the arm in everyday life, the advantage seen for some patients with enhanced therapy at six months after stroke had diminished to a non-significant trend by one year. This was due to some late improvement in the conventional therapy group whereas the enhanced therapy group remained static or fell back slightly. It is recommended that trials should be conducted comparing very intensive therapy for the arm with controls without treatment. This would provide a model of the effects of therapy on intrinsic neural recovery that would be relevant to all areas of neurological rehabilitation.     

The stroke caregiving trajectory in relation to caregiver depressive symptoms,burden, and intervention outcomes

Background: Caregiver depression and burden have a detrimental effect on stroke survivors’ rehabilitation and are contributors to stroke survivors’ hospital readmission and institutionalization. The stroke caregiving trajectory is unique compared to other illnesses, and the effect of length of caregiving on stroke caregiver outcomes is poorly understood. Interventions can improve caregiver outcomes, but the optimal timing of these interventions is unclear.

Objectives: We sought to determine the relationship between: (1) length of caregiving and stroke caregiver depressive symptoms and burden, and (2) length of caregiving and amount of change in depressive symptoms and burden following the Resources and Education for Stroke Caregivers’ Understanding and Empowerment (RESCUE) intervention – an online and telephone problem-solving, education, and support intervention.

Methods: We analyzed retrospective data collected from 72 stroke caregivers who participated in the RESCUE intervention. Outcomes were caregiver depressive symptoms and burden. Data were analyzed using mixed-effects regression analysis.

Results: Baseline depressive symptoms and burden were both negatively related to length of caregiving (p < 0.05). We found significant improvement in caregiver depressive symptoms and burden following an intervention. The interaction between changes in outcomes and length of caregiving was not significant for either depressive symptoms (p = 0.26) or burden (p = 0.10).

Conclusions: This study contributes to the understanding of the relationship between length of caregiving and depression, burden, and intervention outcomes. Clinicians should recognize that the stroke caregiving trajectory can be nonlinear. Routine and repeated clinical assessment of caregiver well-being is needed, along with implementation of interventions when necessary, regardless of how much time has passed since the stroke.     

Pre-admission warfarin use in patients with acute ischemic stroke and atrial fibrillation: The appropriate use and barriers to oral anticoagulant therapy

INTRODUCTION: Warfarin reduces the risk of stroke in patients with atrial fibrillation. Despite strong guideline recommendations, studies continue to demonstrate the under-use of warfarin in clinical practice. PURPOSE: To determine the prevalence and predictors of warfarin use in patients presenting with atrial fibrillation and acute ischemic stroke who do not have a documented contraindication to anticoagulants. METHODS: We conducted a retrospective chart review of all patients admitted to the Hamilton General Hospital with a primary diagnosis of ischemic stroke and a coded diagnosis of atrial fibrillation between 1999 and 2004. Using a standardized data abstraction form, the following variables were recorded: baseline demographics, past medical history including risk factors for stroke and major bleeding and known predictors of warfarin under-use. In cases where warfarin was not prescribed, charts were also reviewed for documented contraindications to warfarin use. The following were considered valid contraindications to warfarin: patient refusal, non-compliance with INR monitoring, bleeding diathesis, history of major bleeding or significant alcohol consumption. RESULTS: In total, 196 patients with ischemic stroke and atrial fibrillation were identified. Of these patients, 106 were considered to be appropriate candidates for anticoagulation after excluding patients with no known diagnosis of atrial fibrillation prior to admission (N=59), a valid contraindication to warfarin use (N=18), a CHADS2 score <1 (N=6) or a competing diagnosis for warfarin use (N=7). Of the patients deemed to be suitable candidates for warfarin, 57 (54%) were receiving warfarin therapy on admission. On multivariable analyses, increasing age (OR 0.7; 95% CI 0.5-0.9) was associated with a reduced odds of warfarin use while a history of stroke or TIA (OR 2.6; 95% CI 1.1-6.5) and a history of congestive heart failure (OR 3.2; 95% CI 1.1-9.0) were associated with an increased odds of warfarin use in patients without a contraindication to warfarin. While 75% of patients <75 years old were anticoagulated, only 33% of those >85 years were prescribed warfarin on admission to hospital. CONCLUSIONS: early half of all patients presenting with atrial fibrillation and acute ischemic stroke who were suitable candidates for anticoagulation were not prescribed warfarin. In patients not prescribed warfarin, very few had a documented contraindication. Advanced age appears to be the strongest predictor of warfarin non-use.