Extravasation of Non-Cytotoxic Drugs in Older People.

Objective To describe the risk factors of extravasation, its impact on the pharmacokinetics of non-cytotoxic drugs, and management of extravasation in older individuals. Extravasation occurs when vesicants leak from blood vessels into surrounding tissue causing severe injury such as tissue necrosis while infiltration is caused by leakage of an irritant that causes injury but does not lead to tissue necrosis. Extravasation occurs in approximately 0.01% to 6% of patients, particularly with cytotoxic agents. However, there is limited documentation about extravasation of non-cytotoxic agents, particularly in older people. Data Sources A literature search of Pubmed and Medline was performed using the following search items: "extravasation," "infiltration," "elderly," and "non-cytotoxic drugs," as well as a combination of these terms. Conclusion It is important to recognize, identify, and manage extravasation early since it can have deleterious consequences for older people. It is more important to prevent extravasation than manage it using standardized evidence-based protocols, and this can be implemented in the nursing facility and acute care setting.

Immune reconstitution following rabbit antithymocyte globulin.

Depletional induction therapies are routinely used to prevent acute rejection and improve transplant outcome. The effects of depleting agents on T-cell subsets and subsequent T-cell reconstitution are incompletely defined. We used flow cytometry to examine the effects of rabbit antithymocyte globulin (rATG) on the peripheral T-cell repertoire of pediatric and adult renal transplant recipients. We found that while rATG effectively depleted CD45RA+CD27+ naïve and CD45RO+CD27+ central memory CD4+ T cells, it had little effect on CD45RO+CD27- CD4+ effector memory or CD45RA+CD31-, CD45RO+CD27+ and CD45RO+CD27- CD8+ T cell subsets. When we performed a kinetic analysis of CD31+ recent thymic emigrants and CD45RA+/RO+ T cells, we found evidence for both thymopoiesis and homeostatic proliferation contributing to immune reconstitution. We additionally examined the impact of rATG on peripheral CD4+Foxp3+ T cells. We found that in adults, administration of rATG-induced peripheral expansion and new thymic emigration of T cells with a Treg phenotype, while CD4+Foxp3+ T cells of thymic origin predominated in children, providing the first evidence that rATG induces Treg in vivo. Collectively our data indicate that rATG alters the balance of regulatory to memory effector T cells posttransplant, providing an explanation for how it positively impacts transplant outcome.

Towards Excellence in Asthma Management: final report of an eight-year program aimed at reducing care gaps in asthma management in Quebec.

BACKGROUND AND OBJECTIVES: Asthma care in Canada and around the world persistently falls short of optimal treatment. To optimize care, a systematic approach to identifying such shortfalls or 'care gaps', in which all stakeholders of the health care system (including patients) are involved, was proposed. METHODS: Several projects of a multipartner, multidisciplinary disease management program, developed to optimize asthma care in Quebec, was conducted in a period of eight years. First, two population maps were produced to identify regional variations in asthma-related morbidity and to prioritize interventions for improving treatment. Second, current care was evaluated in a physician-patient cohort, confirming the many care gaps in asthma management. Third, two series of peer-reviewed outcome studies, targeting high-risk populations and specific asthma care gaps, were conducted. Finally, a process to integrate the best interventions into the health care system and an agenda for further research on optimal asthma management were proposed. RESULTS: Key observations from these studies included the identification of specific patterns of noncompliance in using inhaled corticosteroids, the failure of increased access to spirometry in asthma education centres to increase the number of education referrals, the transient improvement in educational abilities of nurses involved with an asthma hotline telephone service, and the beneficial effects of practice tools aimed at facilitating the assessment of asthma control and treatment needs by general practitioners. CONCLUSIONS: Disease management programs such as Towards Excellence in Asthma Management can provide valuable information on optimal strategies for improving treatment of asthma and other chronic diseases by identifying care gaps, improving guidelines implementation and optimizing care.

Longitudinal study of magnetic resonance imaging and standard X-rays to assess disease progression in osteoarthritis.

OBJECTIVE: To investigate, over 1-year, the relationship between X-ray and magnetic resonance imaging (MRI) findings in patients with knee osteoarthritis (OA). METHODS: Sixty-two osteoarthritic patients (46 women) were followed for 1 year. At baseline and after 1 year, volume and thickness of cartilage of the medial tibia, the lateral tibia and the femur were assessed by MRI. A global score from the multi-feature whole-organ MRI scoring system (WORMS) was calculated for each patient at baseline and after 1 year. This score combined individual scores for articular cartilage, osteophytes, bone marrow abnormality, subchondral cysts and bone attrition in 14 locations. It also incorporated scores for the medial and lateral menisci, anterior and posterior cruciate ligaments, medial and lateral collateral ligaments and synovial distension. Lateral and medial femoro-tibial joint space width (JSW) measurements, performed by digital image analysis, were assessed from fixed-flexion, postero-anterior knee radiographs. RESULTS: One-year changes in medial femoro-tibial JSW reach 6.7 (20.5) % and changes in medial cartilage volume and thickness reach 0.4 (16.7) % and 2.1 (11.3) %, respectively. Medial femoro-tibial joint space narrowing (JSN) after 1 year, assessed by radiography, was significantly correlated with a loss of medial tibial cartilage volume (r=0.25, P=0.046) and medial tibial cartilage thickness (r=0.28, P=0.025), over the same period. We found also a significant correlation between the progression of the WORMS and radiographic medial JSN over 1 year (r=-0.35, P=0.006). All these results remained statistically significant after adjusting for age, sex and body mass index. CONCLUSION: This study shows a moderate but significant association between changes in JSW and changes in cartilage volume or thickness in knee joint of osteoarthritic patients.

Osteoarthritis, magnetic resonance imaging, and biochemical markers: a one year prospective study.

OBJECTIVE: To investigate the relation between biochemical markers of bone, cartilage, and synovial remodelling and the structural progression of knee osteoarthritis. METHODS: 62 patients of both sexes with knee osteoarthritis were followed prospectively for one year. From magnetic resonance imaging (MRI), done at baseline and after one year, the volume and thickness of cartilage of the femur, the medial tibia, and the lateral tibia were assessed. A whole organ magnetic resonance imaging score (WORMS) of the knee was calculated for each patient at baseline and at the one year visits. This score consists in a validated, semiquantitative scoring system for whole organ assessment of the knee in osteoarthritis using MRI. Biochemical markers (serum hyaluronic acid, osteocalcin, cartilage glycoprotein 39 (YKL-40), cartilage oligomeric matrix protein (COMP), and C-telopeptide of type I collagen (CTX-I), and urine C-telopeptide of type II collagen (CTX-II)) were measured at baseline and after three months. RESULTS: Baseline markers were not correlated with one year changes observed in cartilage volume and thickness. However, an increase in CTX-II after three months was significantly correlated with a one year decrease in mean thickness of medial tibial and lateral tibial cartilage. Patients in the highest quartile of three month changes in CTX-II experienced a mean loss of 0.07 (0.08) mm of their medial thickness, compared with a mean increase of 0.05 (0.19) mm for patients in the lowest quartile (p = 0.04) Multiple regression analysis showed that high baseline levels of hyaluronic acid are predictive of a worsening in WORMS (p = 0.004). CONCLUSIONS: These results suggest that a single measurement of serum hyaluronic acid or short term changes in urine CTX-II could identify patients at greatest risk of progression of osteoarthritis.

Teeth grinding, tongue and lip biting in a 24-month-old boy with meningococcal septicaemia. Report of a case.

This paper describes the management of a 24-month-old boy who presented with self-inflicted trauma to his lower lip and tongue, and teeth grinding, 21 days after developing meningococcal septicaemia. A decision to observe and prescribe palliative therapy was made. Extraction of the lower right deciduous canine, which had become non-vital, possibly due to bruxism, was carried out.

Interpreting the International Normalized Ratio (INR) in individuals receiving argatroban and warfarin.

The effects of argatroban, a direct thrombin inhibitor, on the International Normalized Ratio (INR), activated partial thromboplastin time (aPTT) and functional factor X during warfarin co-administration were established to provide means to interpret INRs during argatroban/warfarin co-therapy. Twenty-four subjects receiving warfarin (7.5 mg, day 1; 3-6 mg/day, days 2-10) and argatroban (1-4 microg/kg/min over 5 h, days 1-11) were assessed daily for these coagulation parameters prior to argatroban infusion (warfarin "monotherapy") and at its conclusion ("co-therapy"). Argatroban increased aPTTs dose-dependently. Co-therapy INR increased linearly with monotherapy INR, with slope sensitive to argatroban dose and thromboplastin used. Prediction errors for monotherapy INRs were < or =+/- 0.4 for argatroban 1-2 microg/kg/min but > or = +/-1.0 for higher doses. Despite co-therapy INRs >7, no major bleeding occurred. Factor X remained > or =37% of normal. Therefore, the predictable effect of argatroban (< or =2 microg/kg/min only) [corrected] on INRs during warfarin co-therapy allows for reliable prediction of the level of oral anticoagulation.

Non-traditional study designs to demonstrate average bioequivalence for highly variable drug products.

OBJECTIVE: To demonstrate average bioequivalence, the ninety-percent confidence intervals (CI) on the ratio of geometric means for area under the concentration-time curve (AUC) and maximum observed plasma concentration (Cmax) must lie within 0.80-1.25. Demonstration of average bioequivalence (ABE) for highly variable drug products requires large numbers of subjects in a standard, adequately powered, two-period crossover. METHODS: Application of non-traditional study designs can help to meet this hurdle. Study design and analysis for replicate and group sequential-replicate study designs are presented and illustrated using examples. It is demonstrated how to use such approaches to meet the difficult regulatory hurdle of average bioequivalence for a highly variable drug product. RESULTS: To illustrate, data are provided from three separate ABE studies for a highly variable drug product at three dosage strengths. In all three studies, a replicate study design was used to compensate for high intrasubject variation. Additionally, for the last study, a group sequential study design was imposed to provide early evidence of conclusive results. CONCLUSION: Replicate designs and group-sequential designs in bioequivalence should be used to demonstrate average bioequivalence for highly variable drug products or when uncertain of true intrasubject variability in order to ensure conclusive study results.

Long-term effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis: The Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT).

BACKGROUND: This long-term, multicenter, randomized, double-blind, placebo-controlled, 2 x 2 factorial, angiographic trial evaluated the effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis in normocholesterolemic patients. METHODS AND RESULTS: There were a total of 460 patients: 230 received simvastatin and 230, a simvastatin placebo, and 229 received enalapril and 231, an enalapril placebo (some subjects received both drugs and some received a double placebo). Mean baseline measurements were as follows: cholesterol level, 5.20 mmol/L; triglyceride level, 1.82 mmol/L; HDL, 0.99 mmol/L; and LDL, 3.36 mmol/L. Average follow-up was 47.8 months. Changes in quantitative coronary angiographic measures between simvastatin and placebo, respectively, were as follows: mean diameters, -0.07 versus -0.14 mm (P:=0.004); minimum diameters, -0.09 versus -0.16 mm (P:=0. 0001); and percent diameter stenosis, 1.67% versus 3.83% (P:=0.0003). These benefits were not observed in patients on enalapril when compared with placebo. No additional benefits were seen in the group receiving both drugs. Simvastatin patients had less need for percutaneous transluminal coronary angioplasty (8 versus 21 events; P:=0.020), and fewer enalapril patients experienced the combined end point of death/myocardial infarction/stroke (16 versus 30; P:=0.043) than their respective placebo patients. CONCLUSIONS: This trial extends the observation of the beneficial angiographic effects of lipid-lowering therapy to normocholesterolemic patients. The implications of the neutral angiographic effects of angiotensin-converting enzyme inhibition are uncertain, but they deserve further investigation in light of the positive clinical benefits suggested here and seen elsewhere.

The treatment and prevention of coronary heart disease in Canada: do older patients receive efficacious therapies? The Clinical Quality Improvement Network (CQIN) Investigators.

OBJECTIVES: To review the evidence for clinical efficacy and cost-effectiveness of proven medications in the treatment and prevention of myocardial infarction (MI) in older patients; to summarize Canadian data on treatment patterns and clinical outcomes for younger and older patients with coronary heart disease; to explore the reasons for gaps between best care, based on the evidence of efficacy from trials, and usual care, based on the population effectiveness audits; and to explore potential approaches to closing the care gaps. DESIGN: Review of the recent clinical trial literature on the management of MI, highlighting results in older patients. Review of medication utilization and outcomes data from a series of large, consecutively enrolled patient cohorts with acute MI (N = 7070) in a variety of cardiac care settings (10 centers in five Canadian provinces, including university-based teaching hospitals, community hospitals, cardiologist and family physician out-patient clinics) from 1987 to 1996. RESULTS: There is no qualitative interaction of cardiac therapies: thrombolytics, beta-blockers, acetylsalicylic acid (ASA), and statins are efficacious in all clinically relevant patient subgroups, including older people. However, there are consistent gaps between usual care and best care, particularly among older patients (in whom there is also a concomitantly higher mortality risk). Repeated multivariate analyses confirm older age to be an independent contributor to increased risk. Use of efficacious medications is, in contrast, consistently associated with increased survival. Analysis of temporal trends suggests beneficial changes in practice patterns and outcomes are possible to achieve. However, "best care" has not been rapidly or completely achieved. Review of strategies to close these care gaps suggests that audit and feedback, critical pathways, and multifactorial interventions involving patients and other members of the healthcare team as well as physicians may be the most efficacious strategies for change. CONCLUSIONS: Despite equal or enhanced efficacy, there is consistently less prescription of proven drugs among older cardiac patients. These care patterns may contribute to their enhanced risk. The causes underlying these practice patterns are complex, and their population impact may be undervalued by clinicians and managers. Improvement of these patterns is difficult, but ultimately it would be beneficial for this presently disadvantaged, readily identified, high risk patient population.

Use of nonprescription medications by patients with congestive heart failure.

OBJECTIVE: To define the utilization pattern of nonprescription therapies in patients with congestive heart failure (CHF) and to compare this pattern with that of an age- and gender-matched control group without any self-reported heart conditions. DESIGN: Survey questionnaire completed by participants at home. SETTING: Ambulatory CHF clinic in a tertiary care hospital. SUBJECTS: Patients attending the clinic between July 1995 and May 1996 who agreed to participate. Control subjects were age- and gender-matched participants identified and approached by participating patients. OUTCOME MEASURES: Nonprescription therapies used at least once weekly. RESULTS: Completed questionnaires were received from 180 (75%) of the 239 patients who agreed to participate and from 133 controls. Mean age of responding patients was 69 years (63% men). Controls were younger, with a mean age of 64 years (63% men). The most commonly used nonprescription medication categories for both patients and controls, with no significant intergroup differences, were vitamins and minerals (59% patients, 50% controls), pain relievers (48% and 43%, respectively), herbal or health food products (38% and 38%), antacids (26% and 28%), and laxatives (24% and 21%). Significantly fewer patients than controls used cough and cold products (9% vs. 17%; p < 0.05), specifically oral decongestants (0.6% vs. 5%; p < 0.01), and more patients than controls used nutritional supplements (17% vs. 4%; p < 0.01). CONCLUSIONS: Overall, use of nonprescription therapies by our CHF clinic patients is similar to that of an age- and gender-matched population without a self-reported heart condition. The differences in medication use observed between patients and controls included cough and cold products that might be harmful. This likely reflects appropriate caution with which CHF patients approach nonprescription therapies.

Insights into the contemporary epidemiology and outpatient management of congestive heart failure.

OBJECTIVES: To evaluate the epidemiology, prognosis, and patterns of practice in patients with chronic congestive heart failure (CHF) treated and followed at a specialized clinic. METHODS: Prospective cohort study of consecutive patients referred to and followed up in a specialized heart failure clinic between September 1989 and March 1996. RESULTS: Of the 628 patients referred, 566 were confirmed to have CHF. Mean duration of follow-up was 518 +/- 490 days (range 1 to 2192 days). Vital status was available for 99.3% of patients. Mean age at enrollment was 66 years, 68% were men, 67% had an ischemic cause of heart disease, and 78% had systolic dysfunction. Patients with preserved systolic function were older, more often female, had higher mean systolic blood pressures, and a lower prevalence of ischemic heart disease, ventricular arrhythmias, or impaired renal function when compared with those with systolic dysfunction (all P

A survey of clinician attitudes and management practices in hypertension.

In order to determine the compliance of Canadian physicians with evidence-based hypertension guidelines, a self-administered questionnaire survey was distributed to a stratified random sample of 473 physicians in Central Alberta, Canada in December 1995. Excluding non-deliverable questionnaires, a response rate of 67% was obtained. Twenty-five per cent of respondents routinely used the fourth Korotkoff sound to define diastolic blood pressure (DBP). Investigations recommended for the initial workup of a patient with mild hypertension included serum creatinine (90%), electrolytes (72%), glucose (50%), cholesterol (44%), electrocardiogram (65%), and urinalysis (76%). The non-pharmacologic treatment advice routinely advocated for patients with mild hypertension included salt restriction (87%), weight loss (100%), and regular aerobic exercise (92%). While 46% of respondents recommended antihypertensive therapy for an otherwise healthy patient with an average DBP of 95 mm Hg, 76% recommended therapy for patients with the same BP plus target organ damage or other cardiovascular risk factors. Medication choices varied, although angiotensin-converting enzyme inhibitors were chosen by 46% for patients with uncomplicated essential hypertension and 67% for patients with other cardiovascular risk factors, and beta-blockers were the most frequently chosen first-line agents (56%) for the patient with target organ damage. There was considerable variability in the self-reported practice patterns, and concordance was greater for those recommendations which were consistent across the currently available guidelines. Consistent with the principle underlying all of the current hypertension guidelines, respondents were more aggressive in their treatment of hypertensive patients with other cardiovascular risk factors or target organ damage.

Patient health management: a promising paradigm in Canadian healthcare.

Disease management, or the focused application of resources to achieve desired health outcomes, began in Canada in 1971 with the introduction of a universal healthcare program and a single government payor. Although relatively unfocused and nonrestrictive by contemporary standards, this program was successful in terms of outcomes. However, it is expensive, and Canada's rapidly aging population is fueling a growing demand for more efficacious medical therapies. As a result, isolated services are being restricted in an effort to reduce costs. As a result of these changes and low prescription and patient compliance rates for efficacious therapies, total system costs have risen, there is a growing concern about deterioration of health outcomes, and stakeholders are dissatisfied. To optimize healthcare outcomes and reduce costs, a new paradigm--patient health management (PHM)--has emerged. With PHM, clinical and cost outcomes are continually measured and communicated to providers in an attempt to promote more efficacious care. PHM also seeks to avoid restrictive practices that are now associated with detrimental health outcomes and increased costs. PHM has proved successful when applied to acute and chronic cardiac disease treatment. It remains untested for most other diseases, but available data suggest that the comprehensive, evidence-based disease and systems management that characterizes PHM is likely to achieve the best health outcomes for the most people at the lowest possible costs.

Contemporary practice patterns in the management of newly diagnosed hypertension.

OBJECTIVE: To determine what proportion of patients with hypertension are managed in accordance with guidelines established by the Canadian Hypertension Society. DESIGN: Retrospective medical record review. SETTING: Outpatients seen in primary care offices and internal medicine referral clinics in Edmonton. PATIENTS: All 969 adults who presented with a new diagnosis of essential hypertension from Sept. 1, 1993, to Dec. 31, 1995. OUTCOME MEASURES: Initial laboratory tests performed, advice concerning nonpharmacologic treatment given, antihypertensive drugs prescribed and any contraindications to thiazide diuretics or beta-adrenergic blocking agents documented. RESULTS: The mean age of the 969 patients in the sample was 52.5 years; 129 (13%) of the patients were older than 70 years of age; and 500 (52%) were women. Most of the patients (704, 73%) had mild or moderate diastolic hypertension. In the 617 patients who underwent laboratory tests related to hypertension, the creatinine level was determined in 466 (76%), the cholesterol level in 372 (60%), a urinalysis was conducted in 378 (61%), the serum potassium level was checked in 343 (56%), the sodium level in 323 (52%) and an electrocardiogram was performed in 303 (49%). Liver function tests, which are not recommended in the guidelines, were performed in 338 patients (55%). Although there were differences in prescribing among physicians in the 711 patients given first-line therapy, most (238, 34%) were prescribed angiotensin-converting-enzyme (ACE) inhibitors. Lifestyle modification, without drug therapy, was suggested for 180 (25%) of the patients. Although the guidelines recommend their use for first-line drug therapy, only 82 patients (12%) were given beta-adrenergic blocking agents and only 75 (11%) were given thiazide diuretics. Of the patients who were prescribed an antihypertensive other than a thiazide or beta-adrenergic blocking agent as first-line drug therapy, only 161 (43%) had a documented contraindication to thiazides or beta-adrenergic blocking agents. CONCLUSIONS: There is variation in the contemporary care of patients with hypertension. Further studies are required to determine the reasons underlying physicians' noncompliance with the evidence-based guidelines established by the Canadian Hypertension Society.

Rationale and design features of a clinical trial examining the effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis: Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT). SCAT Investigators.

BACKGROUND: In the treatment of coronary atherosclerotic artery disease (CAD), the mechanisms by which lipid lowering, a proven therapy, produces beneficial clinical effects remain unclear. Moreover, although potential mechanisms of benefit are well known and increasingly applied clinically, there are no conclusive data from clinical trials studying primarily the antiischemic effects of angiotensin-converting enzyme (ACE) inhibition in patients with normal heart function. The Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT) is designed to clarify some of these issues in CAD patients with normal or mildly elevated cholesterol. DESIGN AND OBJECTIVES: SCAT is a three- to five-year, multicentre, randomized, double-blind, placebo controlled, 2 x 2 factorial trial evaluating the effects of cholesterol lowering therapy by simvastatin and/or ACE inhibition by enalapril on anatomic coronary atherosclerosis progression assessed by quantitative coronary angiography in CAD patients with preserved left ventricular function and total cholesterol levels between 4.1 and 6.2 mmol/L. PATIENTS: Of 460 patients (age 61 +/- 9 years; 409 males, 51 females) enrolled between June 1991 and July 1995, 230 were randomized to simvastatin and 230 to placebo, and 229 to enalapril and 231 to placebo. Average baseline total cholesterol level was 5.20 +/- 0.61 mmol/L, high density lipoprotein cholesterol was 0.99 +/- 0.25 mmol/L, low density lipoprotein cholesterol was 3.36 +/- 0.57 mmol/L and triglycerides were 1.82 +/- 0.75 mmol/L. The trial will be completed in June 1998. SIGNIFICANCE: Insights gained from this long term angiographic trial will lead to a better understanding of the mechanisms of benefits of these two treatments, both alone and in combination. Of particular interest is that this trial will be able to examine a suspected beneficial interaction, if present, between these two treatments.

Quantitative relation of electrocardiographic and angiocardiographic measures of risk in patients with coronary atherosclerosis. Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT) Investigators.

OBJECTIVE: To correlate angiocardiographic and electrocardiographic (ECG) measures of risk in coronary artery disease (CAD) patients. SETTING: Baseline substudy of the Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT), a 2 x 2 factorial, randomized, controlled trial of CAD regression. PATIENTS: One hundred and twenty-three CAD patients, 113 males and 10 females; average age, 59 years. METHODS: Bivariate correlations of multiple quantitative measures of epicardial coronary angiographic luminal narrowing (quantitative coronary angiography [QCA]) and body surface ECG maps of the sum of the decrease in the potential time integral of the ST segment (SST decrease) between rest and symptom-limited exercise and between rest and 1 and 5 mins postexercise recovery. RESULTS: The average number of epicardial coronary segments analyzed per patient was 12. The mean diameter averaged 2.78 mm; the minimal diameter, 2.01 mm. The mean percentage coronary stenosis averaged 29.6% and the most severe averaged 62.9%. sigma ST decrease averaged -5323 microV.s between rest and peak exercise and recovered slowly, averaging -5117 microV.s at 1 min postexercise and -4562 microV.s at 5 mins. No QCA measure correlated with any ECG variable (range of r, 0.002 to -0.179; not significant). CONCLUSIONS: Among CAD patients there are no close, or causal, relations between angiographic measures of anatomic epicardial coronary atherosclerosis and ECG functional measures of exercise-induced myocardial ischemia. These data suggest that demonstrated values of stress ECG and coronary angiography for the prediction of clinical risk in CAD patients are largely independent of each other.

The promise and practice of cardiovascular risk reduction: a disease management perspective. Clinical Quality Improvement Network (CQIN) Investigators.

OBJECTIVE: Interpretive analysis of epidemiological, clinical trials and practice pattern data for cardiovascular risk reduction in the contemporary setting of unprecedented demographic changes. DATA SOURCES: Literature review and audit results of the Clinical Quality Improvement Network (CQIN). DATA SYNTHESIS: Coronary artery disease (CAD) is the largest single cause of death in Canada. CAD is age-related and the population is rapidly ageing, a combination that threatens an epidemic of future CAD events. Epidemiological data demonstrate a direct relation of CAD risk and serum cholesterol levels and no threshold cholesterol level below which there is no CAD risk. The epidemiological data also suggest CAD risk can be reduced by lowering serum cholesterol and this hypothesis has now been incontrovertibly confirmed by repeated randomized clinical trials. Most recently, reduction of all-cause mortality with cholesterol-lowering therapy in high risk subjects has also been confirmed. Despite the overwhelming trials and epidemiological evidence, CQIN effectiveness analyses reveal far from optimal risk assessment and management practices among high risk patients. CONCLUSIONS: Serum cholesterol is directly related to CAD risk. Reduction of cholesterol reduces CAD, and all-cause, mortality in high risk patients. There is a large window of opportunity to improve lipid-lowering practices, and patient outcomes, for the most deadly diseases in our society.

Cause-specific noncardiac mortality in patients with congestive heart failure--a contemporary Canadian audit. Clinical Quality Improvement Network (CQIN) Investigators.

BACKGROUND: Noncardiac mortality in congestive heart failure (CHF) is substantial. OBJECTIVE: To define the specific causes of noncardiac mortality among hospitalized CHF patients. DESIGN: Retrospective medical record audit. SETTING: Three hospitals in British Columbia and Alberta, 1992-93. PATIENTS: A total of 2216 consecutive patients admitted with CHF. MAIN RESULTS: The overall mortality rate was 404 of 2216 (18%). Cause of death was cardiac in 290 of 404 (72%) patients, with an average age of 76 years. However, 114 of 404 (28%) deaths, in patients with an average age of 69 years, had noncardiac causes. Four causes accounted for almost 70%, of the noncardiac deaths: cancer (24%); pneumonia (16%); other pulmonary diseases, including embolism (15%); and cerebrovascular disease (11%). Renal disease (9%), gastrointestinal disorders (9%), non-pulmonic sepsis (7%), multiple system failure (5%) and trauma or surgical complications (4%) accounted for most of the remaining noncardiac deaths. CONCLUSIONS: Noncardiac causes produce a substantial proportion of deaths among elderly and sick CHF patients. As the survival of patients with CHF improves, the relative risk of noncardiac mortality in this population will likely increase. However, since hospitalized CHF patients so closely reflect their general population counterparts in terms of cause-specific mortality risk, the search for an ideal therapy might be viewed as a quixotic search for the cure of death.