Medical Practice

Anaphylactoid reactions to alteplase in stroke patients

Hypersensitivity reactions to recombinant tissue plasminogen activator (rt-PA, alteplase) occur in less that 0.02% of patients treated for acute myocardial infarction. Yet, among 105 patients given alteplase intravenously for acute stroke, two had lingual angioedema, which progressed to a fatal anaphylactoid reaction in one. The authors review the two cases and possible mechanisms. Since submission of this article they have observed two further cases of angioedema. They warn that patients who are taking an angiotensin-converting-enzyme inhibitor may be at increased risk for angioedema with concomitant alteplase therapy. CMAJ 2000:162(9):1281-4.

Controversy continues over stroke treatments

Two authors reviewed some of the evidence and the controversies surrounding carotid angioplasty and stenting. Studies of selected patients who underwent this procedure have reported technical success rates of 83 to 99% and combined stroke and death rates of 1.4 to 9%. Issues such as the use of down-stream ballooning, the need for stenting after angioplasty and the true incidence of embolic events associated with carotid angioplasty and stenting still need to be resolved. Until the results of large randomized trials become available, the authors advise that the procedure be reserved for patients with significant contraindications to surgery. CMAJ 2000;162(10):1451-4.

Chest pain and cardiac markers

Researchers conducted a randomized controlled trial involving 296 patients with chest pain and a nondiagnostic electrocardiogram to investigate whether the addition of two new cardiac markers (baseline cardiac troponin I and myoglobin and two-hour myoglobin) to the standard panel (baseline creatine kinase [CK] and CK MB fraction) would result in improved clinical decisions in the emergency department. They found no difference in the length of stay in the emergency department between patients randomly assigned to have the standard panel of cardiac markers and those assigned the enhanced panel. Fewer patients in the latter group were admitted to the cardiology service (46% v. 54%), but the difference was not significant (8.1%, 95% confidence interval –3.3 to 19.5). At 30 days the proportions of patients with a diagnosis of recurrent angina or an acute myocardial infarction were similar in the two groups. The authors conclude that the additional markers did not substantially change clinical management. CMAJ 2000;162(11):1561-6.

Dialysis use rises

The use of dialysis has more than doubled in the past decade, the Canadian Organ Replacement Register reports, with 12,808 Canadians undergoing hemodialysis or peritoneal dialysis in 1998. The national rate of 421.6 cases per mission population marks a 107% increase over the past decade. CMAJ 2000;163(3):319.

Differing opinions about ear tubes

Rates of bilateral myringotomy and tympanostomy tube insertion in children vary widely by region. Researchers surveyed Ontario otolaryngologists to measure the extent of agreement on 17 potential indications for this surgery. Using 90% concordance as a definition of clinical agreement, the 121 eligible respondents agreed on only six of 17 factors and on the management of only one of four clinical vignettes. Given the lack of consensus, the authors suggest that it is time to revisit clinical practice guidelines for this procedure. CMAJ 2000;162(9):1285-8.

Dramatic drop in heart attack mortality

A patient hospitalized with acute myocardial infarction (AMI) in the year 2000 has a markedly improved chance of survival than would have been possible 10 or even five years ago. While most studies of treatment outcomes of AMI have been on selected patient samples, a new study reviewed the cases of all patients in a Quebec government database who had an AMI between 1988 and 1995. The authors found that all-cause 1-year mortality dropped from 23% in 1988 to 19% in 1994; in hospital mortality declined from 14% to 11% and 30-day mortality from 15% to 12%. The authors report that these findings parallel an increase in the use of intensive cardiac procedures such as cardiac catheterization, angioplasty and coronary artery bypass surgery. Prescriptions for acetylsalicylic acid (ASA), beta blockers, lipid-lowering agents and angiotensin-converting enzyme inhibitors increased, while prescriptions for nitrates and calcium antagonists decreased. While the authors caution that definitive conclusions cannot be drawn from their findings, databases from Canadian provinces can provide detailed, albeit descriptive, analyses at the population level. CMAJ 2000;163(1):31-6.

A related commentary contends that increased use of thrombylitic agents and angiography and revascularization procedures are likely the major factors associated with improved outcomes in AMI patients. The author also cautions, however, that quick recognition of the symptoms of an AMI and getting the patient to medical care promptly remains the most important key to a successful outcome. CMAJ 2000;163(1):41-2.

First Canadian live-donor lung transplants performed

Canadian medical history was made in Winnipeg in December, 1999, with the first lung transplant that used healthy, single lobes from two living donors. A second live-donor lung transplant has since been performed by a team at the Health Sciences Centre. The first patients was discharged, but the second has since died of cardiac complications. CMAJ 2000;162(9):1339.

Helping stroke victims beat the clock

Clot-busting drugs have recently been conditionally licensed for use in Canada (February 1999) for the treatment of acute ischemic stroke. However, since these drugs must be administered within three hours of stroke onset, a tremendous amount of organization and cooperation is required to ensure that the patient receives the therapy in time. The Calgary Regional Stroke Program found that beating the clock depended on quick implementation of the five Rs of acute stroke care — recognition, reaction, response, reveal and reperfusion. Over one year, only six% of patients admitted to hospital received the clot-reducing agent tissue plasminogen activator (tPA), primarily due to delays in arrival at hospital and the difficulty in establishing the time of symptom onset.

The researchers identified several barriers, outcomes and lessons during their study, which sought to streamline health system factors ranging from emergency medical services response time to ensuring a bed was available for immediate treatment for stroke victims. The authors report that while stroke victims can be treated safely and successfully, this treatment depends on intense cooperation and organization among all members of the health care team and — most importantly — the patient getting to the hospital in time. CMAJ 2000;162(11):1589-93.

Infectious disease and coronary artery disease

The link between infectious disease and atherosclerosis has existed for over a century. Postulated mechanisms range from direct invasion of the vessel wall to local release of endotoxin to the systemic activation of inflammatory modulators and procoagulants. The agents or conditions most studied are Chlamydia pneumoniae, cytomegalovirus, Helicobacter pylori and periodontitis. A review of the epidemiological, pathological and microbiological evidence, identifies a number of issues to be resolved before the empiric use of antibiotics for CAD is warranted. CMAJ 2000;163(1):49-56.

In praise of tomatoes

Chronic illnesses, including cancer and cardiovascular disease, are the main causes of death in developed countries. Along with genetic factors and age, lifestyle and diet are also considered important risk factors for these diseases. For instance, about 50% of all cancers have been attributed to diet. Oxidative damage to cells is thought to be part of the mechanism behind several chronic diseases. Dietary antioxidants such as the common tomato have been identified as some of the strongest antioxidants and lycopene, a carotenoid pigment found in red fruits and vegetables, is one of the most potent antioxidants known. Two researchers reviewed the mechanism of action and the evidence for the protective effect of a diet high in lycopene, a carotenoid pigment found in red fruits and vegetables. They conclude that while dietary recommendations to increase the consumption of fruits and vegetables rich in antioxidants has generated interest in the role of lycopene in disease prevention, further research is critical to spell out the role of this disease fighter and to formulate guidelines for healthy eating. CMAJ 2000;163(6):739-44.

Kawasaki disease

Kawasaki disease is the leading cause of acquired heart disease in children in the developed world, with coronary artery aneurysms occurring in up to 25% of untreated cases. By surveying all Ontario hospitals and pediatric cardiologists, researchers identified 430 cases of Kawasaki disease in Ontario diagnosed between 1995 and 1997. A diagnosis of typical Kawasaki disease is established in children with a fever and at least 4 of 5 principal clinical features. Yet in the Ontario survey 31% of the children less than one year and more than nine years old had atypical disease. The authors provide a comprehensive review of the recognition and management of the disease. CMAJ 2000;162(6):807-12.

Length of hospital stays drops

Data from the Canadian Institute for Health Information indicate that the average length of a hospital stay in Canada dropped by more than five% between 1994-95 and 1997/98, falling from 7.4 days to seven days. CMAJ 2000;163(4):436.

Lipid guidelines’ accuracy in predicting risk

Although lipid-lowering treatment is indicated for people with cardiac disease, primary prevention of cardiovascular disease is more problematic because such disease may never develop in many people with lipid abnormalities. Researchers in Montreal, Ottawa and Vancouver evaluated the accuracy of the 1998 Canadian lipid guidelines for predicting people at high risk for coronary artery disease. They found that counting risk factors was less accurate than calculating risk using Framingham risk equations, particularly for women, and that the 1998 guidelines identified high-risk people more accurately than previous guidelines. The authors estimate that 5.9 million Canadians currently free of cardiovascular disease would be eligible for screening and 322,705 (5%) would require lipid therapy. CMAJ 2000;163(10):1263-9.

Minimal access surgery centre

A new centre for minimal access (keyhole) surgery training at St. Joseph’s Hospital in Hamilton is designed to provide residents, surgeons and nurses from across Canada with the latest state-of-the-art techniques. CMAJ 2000;162(3):390.

Noninvasive positive-pressure ventilation

The use of noninvasive positive-pressure ventilation (NIPPV) instead of intubation in cases of acute respiratory failure has become more widespread over the past decade, but its use and outcomes in the clinical setting are uncertain. Researchers reviewed the records of consecutive patients treated with over 15 months in a Canadian teaching hospital in an attempt to answer these questions. While NIPPV has been shown to decrease mortality and the need for endotrachial intubation in patients with respiratory failure, the authors found that mortality was 28.6% higher in their observed clinical setting than in randomized trials. They report that many factors likely contributed to this difference, including the experience and training level of the physician initiating the treatment. They recommend the development of a multidisciplinary educational practice guideline as a method to optimize the use of NIPPV. CMAJ 2000;163(8):969-73.

A related commentary addressed the pitfalls of leaning to heavily on the findings of randomized trials in a clinical setting. CMAJ 2000;163(8):986-7.

Necrotizing fasciitis in children

Early recognition is a key to successful treatment of necrotizing fasciitis, the rapidly progressive necrotic soft-tissue infection that has a mortality rate of from 24% to 58%. Researchers report that the number of cases of necrotizing fasciitis in the Ottawa area have increased over the past 16 years and identify the keys to making early recognition and treatment possible. They compared the features of eight pediatric cases of the disease with those of control subjects admitted and treated for cellulitis. The key signs are a generalized rash, a "toxic" appearance, a history of fever and a lower platelet count. CMAJ 2000;163(4):393-6.

Plastic clips pose dangers

Researchers describe five cases in which a plastic bread-bag clip was found in the gastrointestinal tract of patients at a London teaching hospital from 1991 to 1998. In three of the cases the patients presented with a small-bowel perforation and in two the clips were found incidentally. The authors postulate that elderly patients with dentures might be at increased risk for accidental ingestion. To counter accidental ingestion, the authors recommend either the elimination or redesign of bread-bag clips. CMAJ 2000;162(4):527-9.

Rheumatology

At least 10% of patients with clinical presentations to primary care physicians have musculoskeletal complaints. Almost 50% of elderly people have symptomatic disease, and 25% of these patients are disabled. However, in medical school, only three% of the curriculum before clinical training is dedicated to musculoskeletal disease, and only 12% of medical schools have mandatory clinical training in this area. In recognition of the need for an update on diagnosis and management of rheumatological disease, CMAJ launched a new Clinical Basics series on rheumatology. CMAJ 2000;162(7):1007.

Should we screen for hyperhomocysteinemia?

Does altered homocysteine metabolism play a role in the pathogenesis of cardiovascular disease, or is it simply a nonspecific marker of vitamin deficiency? The Canadian Task Force on Preventive Health Care reviewed the evidence. Retrospective case–control studies revealed that patients with coronary artery disease (CAD) had significantly higher fasting plasma total homocysteine (tHcy) levels and post-methionine load tHcy levels than patients without CAD. Prospective studies revealed a dose–response relation between tHcy levels and CAD events and mortality among patients with vascular disease; however, the association in healthy patients was less consistent. A meta-analysis showed that folic acid reduced tHcy levels by 25% on average in people with or without vascular disease. Although insufficient evidence was found to recommend the screening or management of hyperhomocysteinemia, the task force encourages adherence to the recommended daily allowance of folate and vitamins B₆ and B₁₂. CMAJ 2000;163(1):21-9.

An accompanying commentary discusses the treatment dilemmas as physicians await the results of at least 12 large studies underway in the United States, Canada and Europe. CMAJ 2000;163(1):37-40.

Signposts of stroke

Researchers tested a panel of 4 biochemical markers in a series of blood samples from 28 patients with confirmed ischemic stroke. On admission to hospital elevated levels of neuron-specific enolase were found in 89% of the patients, thrombomodulin in 43%, myelin basic protein in 39% and S-100ß. The authors hope their continuing research will determine whether the panel may help to diagnose stroke in the first few hours of onset, when thrombolytic therapy might be indicated, or when stroke subtypes may be identifiable. CMAJ 2000;162(8):1139-40.

Sudden neck movement and cervical artery dissection

Two recent deaths from the snapping of arteries following neck manipulation by chiropractors focused media and medical attention on the relation between sudden neck movement and cervical artery dissection. Over the past year the Canadian Stroke Consrotium has prospectively collected detailed information on 74 cases of the cutting of a cervical artery dissection. The average age of patients in these cases was 44 years and most of the injuries (81%) were associated with sudden neck movements ranging from therapeutic neck manipulation to a vigorous game of volleyball. CMAJ 2000;163(1):38-9.

Total joint replacement

In BC alone 2,600 hip replacements and 2,100 knee replacements were performed in 1997. Researchers at the University of British Columbia point out that disorders requiring joint replacement are not restricted to elderly people. Congenital or developmental dislocations of the hip or trauma may cause degenerative joint disease, and total hip arthroplasty may be required for maximum pain relief. Trivial knee injuries in young people may eventually lead to degeneration of the joint and the need for a knee replacement. Thus, most primary care physicians will deal with patients who have undergone or are likely to require joint replacement. When should a patient be referred for total joint replacement? The authors suggest the main indication continues to be pain. They also describe total hip and knee arthroplasty, the postoperative care that is required and potential complications. CMAJ 2000;163(10):1285-91.

Venous thromboembolism

Hereditary abnormalities in proteins involved in the clotting cascade are associated with increased risk of venous thromboembolism; however, certain of these, such as Factor V Leiden, are prevalent in the asymptomatic population. What, then, is the significance of an abnormal laboratory result? What should drive decision-making about prophylactic anticoagulation, with its attendant side effects? A researcher reviews the risk factors for thromboembolism. CMAJ 2000;163(8):991-4.

Other researchers consider the current state of knowledge about the reliability of laboratory assays in predicting risk and propose criteria by which to evaluate new laboratory tests. CMAJ 2000;163(8):1016-21.

When should hypertension be treated?

Although the efficacy of antihypertensive therapy is well established, not every physician agrees on the thresholds for patients with uncomplicated, mild essential hypertension. In these circumstances individual doctor and patient preferences are liable to be influential. Researchers measured the minimal clinically important difference as perceived by patients and physicians. In general, physicians accepted a smaller difference than did patients; however, there was wide variability in response, including a subset of patients apparently willing to accept therapy without demonstrable benefit. CMAJ 2000;163(4):403-8.

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