Findings of a Provocative New Meta-Analysis

Jason M. Burstein, MD
Internal Medicine Resident,
University of Toronto,
Toronto, ON.

Shabbir M.H. Alibhai, MD, MSc, FRCP(C)
Clinical Assistant, Internal
Medicine & Geriatrics,
University Health Network, Toronto, ON.

Introduction
Atrial fibrillation is a common cardiac condition that challenges many physicians, including primary care and emergency doctors, general internists, geriatricians and cardiologists. One of the best-understood and most studied complications is cardio-embolic stroke. While management of atrial fibrillation may seem straightforward, it is interesting to note that there are still large variations in practice patterns, and a recent meta-analysis was contradictory to many previous studies and guidelines. This paper will focus on the epidemiology and treatment of atrial fibrillation in the older population and will examine both the reasons for variations in practice pattern and the conflicting evidence in major medical journals.

Epidemiology and Causes of Atrial Fibrillation
Age is perhaps the most important influence on the incidence and prevalence of disease. The prevalence rate of atrial fibrillation is 2-3% at age 60 to 65 and 8-10% at age 80. Up to 70% of all affected patients are at least 65 years old. The incidence of atrial fibrillation before age 50 is 0.

Dr. Angela G. Juby, MBChB, Cert Geriatrics
Associate Clinical Professor, Division of Geriatrics,
Department of Medicine, University of Alberta, Edmonton, AB.

Dr. Paul Davis, MBChB, FRCP, FRCPC
Associate Dean, Faculty of Medicine, University of Alberta,
Professor, Division of Rheumatology,
Department of Medicine, University of Alberta, Edmonton, AB

Introduction
Rheumatoid arthritis most commonly presents in the 3rd and 4th decades of life; elderly patients with initial presentation and patients whose disease persists into the later decades of life can present interesting challenges. In particular, the differences in clinical presentations of rheumatoid disease in the elderly when compared to younger patients may lead to difficulty in making a definitive diagnosis. There may be diagnostic challenges related to the interpretation of laboratory findings, particularly serological tests. Elderly patients often have comorbidities; therefore, pharmacologic management of rheumatoid disease must be undertaken with caution to reduce interference with the stability of other organ system therapies, and the potential for drug-disease and drug-drug interaction and polypharmacy must be addressed. Finally, it is important to dispel the attitude that "arthritis" is a process associated with "normal aging.

Jerry Tenenbaum, MD, FRCPC
Rheumatologist,
Mount Sinai Hospital and
Baycrest Centre for Geriatric Care,
Associate Professor,
University of Toronto,
Toronto, ON.

Introduction
Osteoarthritis (OA) is a chronic disease of the joint that results in degeneration of the cartilage and bone. However, in osteoarthritis, it is not uncommon to see intermittent or even chronic evidence of inflammation in the affected joint. Patients may experience stiffness after immobility (in the morning or after sitting for a long time), warmth and erythema of the joint, and soft tissue swelling and/or synovial effusion. On history taking and physical exam, these findings attest to the inflammatory nature of the involved osteoarthritic joint at the time. A microscopic examination of the synovium of patients with osteoarthritis will often show the presence of inflammation. Though cartilage and bone seem to be the primary targets of damage, it is likely that inflammation within the synovium may play an important role in the progressive damage to these joint tissues. Primary involvement of synovium may occur in some patients and secondary synovitis is commonly seen. This is associated with the intermittent or chronic presence of crystals (calcium pyrophosphate dihydrate, hydroxyapatite) or synovitis associated with stimulation by joint damage debris.

A. Mark Clarfield

Several years ago at a public ceremony, a member of Europe's royalty forgot where she had put her reading glasses. Her husband may have thought that his regal spouse was showing signs of early Alzheimer's disease. However, Her Royal Highness clearly remembered that she wore glasses. In this distinction lies the difference between normal aging and dementia.

However, when the family doctor is concerned that a patient is suffering from one of the dementias--an insidious loss of higher cerebral functions including memory, judgment, affect, orientation, behaviour and language skills--further differentiation must be made. Most demented patients suffer from Alzheimer's disease or from brain damage resulting from multiple strokes. Unfortunately, in either of these situations there are few available treatments that can either reverse or limit the ongoing brain damage. For a fortunate few with a reversible cause for the dementia, early treatment can actually result in a significant improvement in the cognitive dysfunction.

Only a decade ago, the highest medical authorities held that anywhere from 20-40% of dementias were reversible. However, meta-analyses of the data indicated that reversibility occurred in no more than 11% of cases.^1,2 Even more recent community-based studies indicate that, unfortunately, most dementias are incurable (although certainly not unmanageable); probably less than 1% fall into the reversible category.

Bob Chaudhuri, MD
Resident in Psychiatry,
Department of Psychiatry,
University of Toronto.

In 1990, three million members of the US population were 85 years of age or older. By the year 2050, it is expected that the numbers of these very elderly people will reach 20 million. However, the percentage of older people in the US is less than that in most European nations. If one considers developing nations, 250 million Chinese will be over the age of 60 by the year 2020, and the number of people in developing nations over the age of 60 will be greater than that number in all the countries in Europe. Importantly, the number of people over the age of 80 continues to grow in proportion to the nation's population.¹ Given these demographic numbers,² the sequella of aging is relevant to psychiatry in general and geriatric psychiatry specifically. There is no specific Canadian data on this subpopulation.

Dementia is primarily a disease of later life, affecting approximately 5% of people over the age of 65, and in some populations studied, almost 50% of those over the age of 85. The essential features of dementia include the development of multiple cognitive deficits including, memory impairment, disturbance in executive functioning, and at least one of aphasia, apraxia or agnosia.

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

Introduction
Agitation is an aspect of dementia that can have serious emotional, medical and health-care system consequences. It results in decreased quality of life for both patient and caregiver and is often cited as the reason for the patient being admitted to a long-term care facility. Within the nursing home setting, agitation may often result in increased use of physical and/or chemical restraints, with concomitant problems such as physical injury and falls. Medical care of the agitated patient can be compromised and nursing staff is required to spend greater amounts of time caring for the agitated patient.

Definition and Prevalence
Allen (1999) points out that "agitation" is not a diagnosis but refers to a constellation of symptoms.¹ Cohen-Mansfield and Billing (1986)² define agitation as "inappropriate verbal, vocal or motor activity unexplained by apparent needs or confusion." These authors divide the symptoms of agitation into three: aggressive behaviours (hitting, kicking, verbal aggression, spitting); inappropriate physically non-aggressive behaviours (pacing, repetitious mannerisms, robing and disrobing); and inappropriate verbal agitated behaviours (screaming, complaining, constant demands for attention).

Chris MacKnight, MD, MSc, FRCPC
Division of Geriatric Medicine,
Dalhousie University,
Halifax, NS.

Dementia and hypertension are two of the most common conditions affecting older adults. A number of recent studies suggest that dementia is one of the long-term complications of hypertension. Studies also suggest that the treatment of hypertension may prevent dementia. This brief review will focus on the relationship between hypertension and dementia in older adults.

Epidemiology of Dementia
Eight percent of Canadians who are over the age of 65 suffer from dementia, with Alzheimer's disease being the most common cause (approximately 60% of cases).¹ Dementia is age-related, with the prevalence increasing from 2.4% of those from 65-74 years of age, to 34.5% of those 85 and older. Sixty thousand new cases occur each year in Canada.² The cost of providing care to these patients is substantial, at 3.9 billion dollars/year, in 1991 dollars.³ Vascular dementia is the second most common cause of dementia in Canada, accounting for 20% of cases. When discussing vascular dementia, it is important to recognize that the classic pattern of multiple infarcts is found only in approximately 1/3 of the cases. The other cases consist of patients who have changes in their white matter (likely on the basis of small vessel ischemia) with or without lacunar infarcts, or, rarely, single strategic strokes.

Two studies, recently published in the New England Journal of Medicine, have suggested a role for radiation therapy in the treatment of restenosis. Every year, thousands of patients undergo balloon angioplasty to open clogged arteries. In 60% of these cases, physicians also insert a stent to keep the artery propped open. Unfortunately, in 35% of cases, restenosis occurs and the patient has to undergo another angioplasty or a bypass operation. Both studies investigated the use of placing radioactive materials into the arteries for a short period of time, and then removing them. Where the studies differ is in the type of radiation that is used. In the first study, the researchers used beta radiation, considered safer because it does not penetrate past the body of the patient. In the second study, gamma radiation was used, and health-care workers had to be shielded.

In the study of beta radiation, 181 patients were treated who had undergone angioplasty for the first time. Once the blockage had been cleared, a radioactive coil was inserted into the artery and was subsequently removed, after a few minutes. Patients were given heart scans six months later and it was found that restenosis had occurred in only 29% of patients who had received the lowest dose of radiation, and in 15% of those who had received a dose that was two times as high.

In the second study, patients had already undergone a previous angioplasty procedure. In 131 patients, after undergoing a new angioplasty, a tiny ribbon containing gamma radiation was inserted and was removed after 20 minutes. In another 121 patients, the procedure was replicated with an identical looking ribbon that contained no radiation. At 6 months post-procedure, 28% of the patients in the radiation treatment group had restenosis, as compared to 44% in the comparison group. Unfortunately, several months after the procedure, 5% of radiation patients developed dangerous blood clots, as compared to only 1% in the control group.

The technique would mean that many patients could be spared bypass surgery or repeated angioplasties, but is obviously associated with several caveats. Further studies with larger numbers of patients are required before any definitive conclusions can be made regarding the effectiveness of the technique. In addition, the possible development of cancers, as a side effect of the radiation treatment in these patients, is of major concern.

Sources

1. Verin, V et al. Endoluminal Beta-Radiation Therapy for the Prevention of Coronary Restenosis after Balloon Angioplasty. NEJM 2001;344:243.
2. Leon, MB et al. Localized Intracoronary Gamma-Radiation Therapy to Inhibit the Recurrence of Restenosis after Stenting. NEJM 2001;344:250.

Dimitrios G. Oreopoulos
Nada Dimkovic
Toronto Western Hospital,
University Health Network

Introduction
The elderly (>65 years) are the fastest growing group of patients who require dialysis. In 1988, of the more than four thousand new dialysis patients, one thousand nine hundred and fifty eight were 65 years or older, giving an approximate rate of 515 new patients per million members of the population.

Once an elderly patient has developed end-stage renal disease (ESRD), his/her therapeutic options become limited to the various modes of dialysis that are available and, to a lesser degree, to renal transplantation.

Here we should mention a word of caution with regards to using serum creatinine as a guide for the point at which to begin dialysis. Because of the decrease in muscle mass that is associated with age, serum creatinine is disproportionately low for the degree of renal failure. Rather than relying on serum creatinine, either a creatinine clearance, or the Cockroft-Gault formula should be used to assess the severity of renal failure.

Although renal transplantation may be successful in the elderly person with ESRD, and they may have renal graft and patient survival rates comparable to those of younger recipients, only a small percentage (0.5-3%) of these patients are undergoing transplant procedures. The main reason for this is the shortage of donor kidneys.

Is it Ethical to Use Foetal Tissue for the Treatment of PD?

David Kaplan, MSc(HA)
Joint Centre for Bioethics
Faculty of Medicine,
University of Toronto

Surgical transplantation of foetal brain cells has been reported to substantially improve the symptoms associated with Parkinson's Disease. Parkinson's disease, which is characterized by tremors, muscular rigidity, and akinesia, is believed to result from the deterioration of the brain's dopamine producing cells in the substantia nigra (the neural centre for the initiation and control of movement). This disease afflicts 70,000 Canadians, and unfortunately, approximately ten percent of these patients are refractory to conventional medical therapy. Clearly, new methods to control the disease would be of substantial benefit to these patients. In 1995, the Canadian government introduced legislation that would have made it difficult, if not illegal, to conduct research into foetal tissue transplant. Although this Bill died on the parliamentary order desk, there remains the prospect of reintroducing such legislation. The purpose of this article is to examine the murky ethical waters that surround the topic of research and therapy involving foetal tissue. However, I will not attempt to validate the merits of this therapy in this brief analysis.

Procurement
Obviously, a source of foetal tissue is required, in order to perform foetal tissue transplantation surgery. There are three potential sources for this tissue.