A Review of Efficacy, Toxicity and Safety Considerations

Charles L Bennett, MD, PhD
The Chicago VA Healthcare
System/Lakeside Division, the Robert H Lurie Comprehensive Cancer Center and
the Division of Hematology/Oncology of the Department of Medicine,
Northwestern University,
Chicago, IL, USA.

Richard H Bennett, MD
Department of Neurology,
Albert Einstein Northern Hospital and
the Medical School of the University of Pennsylvania,
Philadelphia, PA, USA.

Introduction
Stroke is a common cause of morbidity and mortality in older adults in the United States and Canada. Fortunately, in both countries, the age-adjusted national death rate for stroke has declined, reflecting increasingly widespread use of primary and secondary prophylaxis efforts. The mainstay of stroke prevention is the use of antiplatelet agents which interfere with thrombus formation by platelets in diseased or damaged blood vessels (see Figure 1). While aspirin has been the primary antiplatelet agent, over the past ten years, ticlopidine (Ticlid), clopidogrel (Plavix) and extended release dipyridamole plus aspirin (Aggrenox) have been approved for use in this setting.

Scott B. Patten, MD, PhD
Associate Professor,
Departments of Community Health Sciences and Psychiatry,
University of Calgary, Population Health Investigator,
The Alberta Heritage Foundation for Medical Research,
Calgary, AB.

Stroke has the potential to disrupt several facets of a person's life including communication, emotional regulation, cognitive function and coping skills.¹ Furthermore, stroke does not just impact on the individual but also on his or her family members and other social networks of which he or she is a part. Stroke has been regarded as form of "double-jeopardy"¹ in the sense that the condition creates many new problems and challenges for those afflicted, and simultaneously detracts from the afflicted persons' capacity to cope with those challenges. It can also lead to disruptions in those same social connections that would normally support adaptation to loss.

Understanding the role of psychosocial factors in recovery from stroke requires adopting a conceptual viewpoint that transcends the traditional biomedical perspective. A suitable framework is provided by the World Health Organization's International Classification of Impairments, Disabilities and Handicaps (WHO-ICIDH). The WHO system differentiates among impairment, disability and handicap. According to the WHO, impairment is defined as any loss or abnormality of structure or function.

Michel Loranger
Martin Doyon
School of Psychology,
Laval University, Laval, QC.

Due to the heterogeneity of their deficits, stroke patients constitute a distinct population within rehabilitation settings. Deficits that follow an acute stroke are mostly related to motor and intellectual performance and, frequently, to cognitive functioning as well. These deficits have tremendous consequences on individuals' global autonomy in completing activities of daily living, as well as on their social and vocational participation.^1-3 Current statistics show that there are nearly 4 million patients in the United States dealing with the consequences of a stroke. Therefore, accurate and reliable assessment of acute stroke prognosis should be of major concern to clinicians.

Accordingly, in its report published in 1989, the World Health Organization (WHO)⁴ encouraged the development of new information and assessment tools in order to guide, support and justify clinical interventions. WHO's model suggests classifying acute stroke patients into three categories according to their potential for recovery:

1. Patients who recover spontaneously without any attempt at rehabilitation;
2. Patients who show a good recovery requiring rehabilitation effort;
3. Patients showing no real improvement independent of the effort made at rehabilitation.

Lin Perry, MSc, RGN, RNT,
Faculty of Health & Social Care Sciences,
Kingston University and St. George's Hospital Medical School:
Sir Frank Lampl Building, Kingston University,
Kingston upon Thames, Surrey, UK.

Introduction
Stroke is a major cause of mortality and morbidity in all industrialized countries¹--incidence of a first-in-a-lifetime stroke in the UK is estimated at 2.4 per 1,000 population per year, with all strokes combined having an incidence 20-30% higher.²

Dysphagia is a frequent accompaniment to stroke.^3-5 Depending upon manner and timing of assessment, dysphagia is detected in 30-65% of acute stroke patients^6-10 with a small proportion experiencing clinically 'silent' aspiration of food/ fluids.^9,10 Dysphagia is associated with increased morbidity and mortality. Whilst this may partly be explained by its relationship with increased stroke severity, dysphagia also exerts an independent effect revealed by the tripling of mortality rates in alert dysphagic stroke patients compared to similar groups with intact swallow.⁸ It is associated with chest infection independent of aspiration⁷ which also risks chemical pneumonitis, infection and airway obstruction.^11,12 Although dysphagia frequently resolves rapidly, for a minority it produces enduring disability and handicap. Stroke-related impaired swallowing has been found in 5.

Eileen P. Sloan, MD, PhD
Resident in Psychiatry,
University of Toronto,
Toronto, ON.

Capgras syndrome is an atypical psychotic disorder, originally described in 1923 by Jean Marie Joseph Capgras, a French Psychiatrist.¹ It is a rare disorder, which probably accounts for the paucity of literature and of systematic study on the topic; a literature search largely produces case reports. It often occurs within the context of other neurological and psychiatric illnesses, such as epilepsy, Parkinson's disease, dementia and schizophrenia.

The characteristic symptom of Capgras syndrome is the delusional belief that other people, usually someone the patient has an emotional relationship with, such as a spouse or child, has been replaced by an impostor, usually one that they consider malevolent. This "double" is physically identical to, but psychologically different from, the replaced relative. The "original" and the "other" always differ in some respect germane to the patient's experience or feelings. The "real" spouse, for example, may have been more affectionate or would have acted differently in a given situation. It seems that the patient does not have difficulty perceiving the subject (e.g. their spouse) but rather can no longer appreciate its emotional significance.

Dr. Ruth Hubbard
Lecturer

Dr. M. Sinead O'Mahony
Senior Lecturer,
University Department of Geriatric Medicine,
University of Wales,
College of Medicine, Wales, UK.

Introduction
Stroke is the second most common cause of mortality in much of the developed world and leads to an estimated 4.4 milllion deaths per year, worldwide.¹ It also causes significant morbidity. Thirty percent of patients with a stroke will die within the first three months and half of the remaining patients will have significant long-term disability.

Stroke is particularly a problem of older people. The risk of stroke doubles with each decade of life after 35 years, such that two thirds of all strokes occur in patients over the age of 65 years. People over 75 years are the fastest growing population in North America. Any treatment that improves outcomes in elderly patients with stroke is potentially of huge importance.

Until recently, there was no effective therapy or management strategy to reduce stroke mortality and disability. Two interventions have been shown to result in some benefit--stroke units and aspirin therapy. Stroke Unit care is associated with 70 fewer deaths or dependencies per 1000 patients treated.

Jocalyn P Clark, MSc, PhD candidate
Department of Health Sciences,
University of Toronto and
The Centre for Research in Women's Health,
Toronto, ON.

Stroke is the third leading cause of death for North American women and the leading cause of long-term disability in Canada. According to the Ontario Ministry of Health and Long-Term Care, in 1994/95 stroke-related costs in the province totaled $857 million. The Canadian Stroke Network estimates annual costs for stroke in Canada to be 2.7 billion dollars. Over the next five years the incidence of stroke is expected to increase by over 30%, and those figures could jump to 68% within two decades. Every year among women, stroke claims more than twice as many lives as does breast cancer. Indeed, according to Dr. Beth Abramson, a cardiologist at St. Michael's Hospital in Toronto and an expert in women and stroke, "The issue of stroke in women is a significant one. This is due to potential bias in treatment of female stroke patients, but also to the greater co-morbidity and health care costs associated with treating women when they suffer from stroke."

Like other cardiovascular conditions, stroke in women is highly age-dependent: women are, on average, several years older than men when they suffer their first stroke and tend to be sicker. Owing to this age dependence, the health burden of stroke will only magnify as the proportion of elderly women in the population increases over time.

Anna Gagliardi, MSc, MLS
Program Manager
Surgical Oncology, Cancer Care Ontario,
Toronto, ON.

A. Denny DePetrillo, MD, FRCSC
Division of Gynecological Oncology,
University Health Network-Princess Margaret Hospital Site,
Toronto, ON.

A projected 134,100 new cases of cancer and 65,300 deaths from cancer will occur in Canada in 2001.¹ Forty percent of men and 35% of women will develop cancer during their lifetime and just over 25% of men and 20% of women will die of cancer. Given better and more widely used screening tests such as mammography for breast cancer and the PSA blood test for prostate cancer, more cases of cancer are being detected. Moreover, mortality from these cancers has decreased because they are being caught at an earlier, more treatable stage.

The incidence of most cancers increases with age and it is estimated that 55% of human cancer occurs in individuals 65 years of age and older. The literature on cancer treatment for the elderly is limited but it has been suggested that this demographic may be subject to underscreening, understaging, less aggressive therapy, lack of participation in clinical trials, or no treatment at all.^2,3 It has been demonstrated that older adults desire curative surgical treatment as much as younger patients, but they believe more strongly that doctors should make treatment decisions, making them more vulnerable to possible age bias.

Katherine Sheehan
University of St. Andrews,
St Andrews, Scotland.

Michael Gordon, MD, MSc, FRCPC
Vice President of Medical Services,
Baycrest Centre for Geriatric Care,
Professor of Medicine,
University of Toronto,
Toronto, ON.

The infection control troops are preparing for battle, waiting for the declaration of war. Once again, it's nearly time for our annual fight against the influenza virus. This potential killer affects hundreds of thousands of Canadians each year, leading to the hospitalization of 75,000 and resulting in 6,700 deaths. Of those who die, 90% are over the age of 65 and about half are residents of long-term care facilities. Elderly residents are particularly vulnerable because of their advanced age, underlying illness, close quarters with other residents and extensive contact with many caregivers.

David J. Gladstone, BSc, MD
Stroke Fellow, Sunnybrook and
Women's College Health Sciences Centre,
University of Toronto,
Toronto, ON.

Cynthia Danells, BScPT
Physiotherapist and Research
Associate,
Sunnybrook and Women's College Health Sciences Centre,
University of Toronto,
Toronto, ON.

Sandra E. Black, MD, FRCPC
Head, Division of Neurology,
Sunnybrook and Women's College Health Sciences Centre, and
Professor of Medicine (Neurology),
University of Toronto,
Toronto, ON.

Delaina Walker-Batson, PhD
The Stroke Center-Dallas,
Professor,
Texas Woman's University, and
Associate Clinical Professor,
Departments of Neurology and Radiology,
The University of Texas Southwestern Medical Center,
Dallas, Texas, USA.

Stroke is a Treatable Condition
Together with advances in the prevention and acute treatment of stroke, the field of stroke rehabilitation is becoming an increasingly exciting frontier for basic science and clinical development (see Table 1). The scientific basis of stroke recovery is becoming better understood, and the post-stroke period is being viewed as an important target for improved therapeutic intervention.