Development and Implementation of a Registry of Patients Attending Multidisciplinary Pain Treatment Clinics: The Quebec Pain Registry.

The Quebec Pain Registry (QPR) is a large research database of patients suffering from various chronic pain (CP) syndromes who were referred to one of five tertiary care centres in the province of Quebec (Canada). Patients were monitored using common demographics, identical clinical descriptors, and uniform validated outcomes. This paper describes the development, implementation, and research potential of the QPR. Between 2008 and 2013, 6902 patients were enrolled in the QPR, and data were collected prior to their first visit at the pain clinic and six months later. More than 90% of them (mean age ± SD: 52.76 ± 4.60, females: 59.1%) consented that their QPR data be used for research purposes. The results suggest that, compared to patients with serious chronic medical disorders, CP patients referred to tertiary care clinics are more severely impaired in multiple domains including emotional and physical functioning. The QPR is also a powerful and comprehensive tool for conducting research in a "real-world" context with 27 observational studies and satellite research projects which have been completed or are underway. It contains data on the clinical evolution of thousands of patients and provides the opportunity of answering important research questions on various aspects of CP (or specific pain syndromes) and its management.

Cost-effectiveness of treating hyperlipidemia in the presence of diabetes : who should be treated?

BACKGROUND: The objective of this study was to estimate the long-term costs and benefits of treating hyperlipidemia among diabetic patients with and without known cardiovascular disease after validating the Cardiovascular Life Expectancy Model. METHODS AND RESULTS: The model estimates were compared with the Scandinavian Simvastatin Survival Study (4S) and used to estimate the long-term costs and benefits of treatment with simvastatin. Simulations were performed for men and women, 40 to 70 years of age, having pretreatment LDL cholesterol values of 5.46, 4.34, and 3.85 mmol/L (211, 168, and 149 mg/dL). We forecasted the long-term risk of cardiovascular events, the need for medical and surgical interventions, and the associated costs in 1996 US dollars. The model validated well against the observed results of the of the 4S diabetic patients. In this validation, the model estimates fell within the 95% confidence interval of the observed results for 7 of the 8 available end points (coronary deaths, total deaths, and so forth). Treatment with simvastatin for patients with cardiovascular disease is cost-effective for men and women, with or without diabetes. Among diabetic individuals without cardiovascular disease, the benefits of primary prevention were also substantial and the cost-effectiveness ratios attractive across a wide range of assumptions ( approximately $4000 to $40 000 per year of life saved). These conclusions were robust even among diabetics with lower baseline LDL values and smaller LDL reductions as observed in the Cholesterol and Recruitment Events (CARE) trial. CONCLUSIONS: Among adults with hyperlipidemia, the presence of diabetes identifies men and women among whom lipid therapy is likely to be effective and cost-effective even in the absence of other risk factors or known cardiovascular disease.

Serum lipid screening to identify high-risk individuals for coronary death. The results of the Lipid Research Clinics prevalence cohort.

OBJECTIVE: To assess the accuracy of specific plasma lipid fractions in predicting coronary heart disease (CHD) mortality among adults. METHODS: Follow-up data for a random sample of 30- to 79-year-old men and women recruited into the Lipid Research Clinics Prevalence and Follow-up Studies were included in this analysis (n = 4499). Baseline measurements of total plasma cholesterol and lipoprotein fractions were compared with subsequent CHD mortality after a mean follow-up of 12.3 years. The areas under receiver operating characteristics curves for specific serum lipids were compared for individuals aged 30 to 59 and 60 to 79 years. MAIN RESULTS: For the younger cohort, the ratio of total cholesterol to high-density lipoprotein cholesterol was a better predictor (P < .05) of CHD mortality (receiver operating characteristic curve area, 0.80 +/- 0.03) than was total cholesterol level alone (receiver operating characteristic curve area, 0.73 +/- 0.03) or any other single lipoprotein measurement. Among the older cohort, the same screening strategies performed poorly, with receiver operating characteristic curve areas ranging from 0.51 +/- 0.05 for total cholesterol to 0.64 +/- 0.05 for the ratio of low-density to high-density lipoprotein cholesterol levels. CONCLUSION: Plasma lipid levels are poor predictors of coronary death among those aged 60 to 79 years without known CHD. These data indicate the need to define better lipid screening strategies for older, asymptomatic adults. Among younger adults aged 30 to 59 years, high-density lipoprotein cholesterol measurement should be included as part of any lipid screening program, as the ratio of total to high-density lipoprotein cholesterol levels is the best lipid screening test to identify those at high risk for subsequent CHD mortality.

Estimating the benefits of modifying risk factors of cardiovascular disease: a comparison of primary vs secondary prevention.

OBJECTIVES: To compare the potential years of life saved (YOLS) associated with risk factor modification in the primary and secondary prevention of cardiovascular disease (CVD). METHODS: The CVD life expectancy model estimates the risk of death due to coronary disease, stroke, and other causes based on the levels of independent risk factors (such as age, blood pressure, and blood lipid levels) found in the cohort of the Lipid Research Clinics. The model was validated by comparing its predictions with the observed fatal outcomes of 9 randomized clinical trials. We then estimated the YOLS associated with treating hyperlipidemia or hypertension among hypothetical patient groups with and without CVD at baseline. We defined high-risk patients as those with 3 risk factors (hyperlipidemia, cigarette smoking, and hypertension) and low-risk patients as those with isolated hypertension or hyperlipidemia. RESULTS: The fatal events predicted by the model were consistent with the clinical trial results. Among men and women with hyperlipidemia without CVD, the forecasted benefits of lipid therapy were substantially greater among high-risk groups vs low-risk groups (4.74-0.78 YOLS vs 2.50-0.25 YOLS, respectively). Among those with CVD, the forecasted benefits of treatment were similar for both high-risk and low-risk groups (4.65-0.65 YOLS vs 3.84-0.58 YOLS, respectively). The results for hypertension therapy also demonstrated greater benefits for high-risk vs low-risk patients undergoing primary prevention therapy (1.34-0.29 YOLS vs 0.85-0.13 YOLS, respectively), and the forecasted benefits in secondary prevention were similar (1.26-0.23 YOLS vs 1.00-0.23 YOLS, respectively). CONCLUSIONS: The clinical approach to risk factor modification in primary prevention should be different from that in secondary prevention. The forecasted benefits of therapy among patients without CVD are greatest in the presence of other risk factors. Among those with CVD, the benefits of therapy are equivalent, thereby obviating the need to target high-risk patients.

Cost-effectiveness of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors in the secondary prevention of cardiovascular disease: forecasting the incremental benefits of preventing coronary and cerebrovascular events.

OBJECTIVE: To forecast the long-term benefits and cost-effectiveness of lipid modification in the secondary prevention of cardiovascular disease. METHODS: A validated model based on data from the Lipid Research Clinics cohort was used to estimate the benefits and cost-effectiveness of lipid modification with 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) based on results from the Scandinavian Simvastatin Survival Study (4S), including a 35% decrease in low-density-lipoprotein (LDL)-cholesterol levels and an 8% increase in high-density-lipoprotein (HDL)-cholesterol levels. After comparing the short-term outcomes predicted for the 4S with the results actually observed, we forecast the long-term risk of recurrent myocardial infarction, congestive heart failure, transient ischemic attacks, arrhythmias, and strokes and the need for surgical procedures such as coronary artery bypass grafting, catheterization, angioplasty, and pacemaker insertions. Outpatient follow-up care costs were estimated, as were the costs of hospital care and drug therapy. All costs were expressed in 1996 US dollars. RESULTS: The short-term outcomes predicted for the 4S were consistent with the observed results. The long-term benefits of lipid modification among low-risk subjects (normotensive nonsmokers) with a baseline LDL/ HDL ratio of 5 but no other risk factors ranged from $5424 to $9548 per year of life saved for men and $8389 to $13747 per year of life saved for women. In high-risk subjects (hypertensive smokers) with an LDL/HDL ratio of 5, the estimated costs ranged from $4487 to $8532 per year of life saved in men and $5138 to $8389 per year of life saved in women. Assuming that lipid modification has no effect on the risk of stroke, cost-effectiveness increased by as much as 100%. CONCLUSIONS: These long-term cost estimates are consistent with the short-term economic analyses of the published 4S results. The long-term treatment of hyperlipidemia in secondary prevention is forecasted to be cost-effective across a broad range of patients between 40 and 70 years of age. Recognizing the additional effects of lipid changes on cerebrovascular events can substantially improve the cost-effectiveness of treating hyperlipidemia.

Life expectancy following dietary modification or smoking cessation. Estimating the benefits of a prudent lifestyle.

OBJECTIVE: To evaluate the maximum benefits of dietary modification or smoking cessation to the life expectancy of North American adults. DESIGN: Using a computer model, we estimated the change in life expectancy for men and women following risk factor modification. We then estimated the total number of adults who would be targeted by national guidelines and the total person-years of life that would be saved. PATIENTS: Men and women aged 30 to 74 years who were free of coronary heart disease. INTERVENTIONS: Smoking cessation or serum cholesterol-reducing diets with 8% to 10% saturated fat and 240 to 300 mg of daily cholesterol, respectively. RESULTS: On average, dietary modification would reduce serum cholesterol levels from 0.45 mmol/L (17.4 mg/dL) to 0.75 mmol/L (29.1 mg/dL) in men and 0.12 mmol/L (4.6 mg/dL) to 0.55 mmol/L (21.4 mg/dL) in women, thereby increasing life expectancy by 0.03 to 0.4 year and 0.01 to 0.16 year, respectively. Smoking cessation would increase life expectancy from 2.59 to 4.43 years among men and from 2.6 to 3.68 years among women. Among adult Canadians, dietary modification would save 373,000 to 683,000 person-years of life. The majority of these benefits would occur among men who start dieting at ages 30 to 59 years. Smoking cessation would add more than 4 million person-years of life to the Canadian population. The relative impact of either intervention among American adults would be similar to these Canadian estimates. CONCLUSIONS: Younger men, aged 30 to 59 years, might live slightly longer after dietary change, but among women and older men the average benefits would be negligible. The benefits of smoking cessation are more uniform across age and sex and are substantially greater than those predicted for dietary change.

How cost-effective is the treatment of dyslipidemia in patients with diabetes but without cardiovascular disease?

OBJECTIVE: Epidemiological studies have shown that the risk of myocardial infarction (MI) in diabetic patients without cardiovascular disease (CVD) is comparable to the risk of MI in patients with CVD. We used a validated Markov model to compare the long-term costs and benefits of treating dyslipidemia in diabetic patients without CVD versus treating CVD patients without diabetes in the U.S. The generalizability and robustness of these results were also compared across six other countries (Canada, France, Germany, Italy, Spain, and the U.K.). RESEARCH DESIGN AND METHODS: With use of the Cardiovascular Disease Life Expectancy Model, cost effectiveness simulations of simvastatin treatment were performed for men and women who were 40-70 years of age and had dyslipidemia. We forecast the long-term risk reduction in CVD events after treatment. On the basis of the Scandinavian Simvastatin Survival Study results, we assumed a 35% reduction in LDL cholesterol and an 8% rise in HDL cholesterol. RESULTS: In the U.S., treatment with simvastatin for CVD patients without diabetes was cost-effective, with estimates ranging from $8,799 to $21,628 per year of life saved (YOLS). Among diabetic individuals without CVD, lipid therapy also appeared to be cost-effective, with estimates ranging from $5,063 to $23,792 per YOLS. In the other countries studied, the cost effectiveness of treating diabetes in the absence of CVD was comparable to the cost effectiveness of treating CVD in the absence of diabetes. CONCLUSIONS: Among diabetic men and women who do not have CVD, lipid therapy is likely to be as effective and cost-effective as treating nondiabetic individuals with CVD.

Delayed diagnosis of gynecologic tumors in elderly women: relation to national medical practice patterns.

PURPOSE: To evaluate the hypothesis that less aggressive cancer screening practices might result in later diagnosis of cancer in the elderly, we analyzed the stage of diagnosis of tumors by age in the Connecticut Tumor Registry. PATIENTS AND METHODS: Using Registry data from 1960 to 1975 and 1976 to 1983, we compared the proportion of tumors that were diagnosed at a localized stage among white women of various age groups. Thirteen specific tumor sites were analyzed, accounting for 55,688 tumors between 1960 and 1975 and 38,715 tumors between 1976 and 1983. RESULTS: Only gynecologic cancers demonstrated a significant inverse relationship between the relative proportion of tumors that were diagnosed at a localized stage and advancing patient age during both time periods. Specifically, when the youngest women (aged 25 to 34) were compared with the oldest women (aged 85 and over), between 1960 and 1975, the relative proportion of localized cervical, uterine, and ovarian cancer dropped from 98 percent to 59 percent, 92 percent to 77 percent, and 59 percent to 27 percent, respectively. Similar declines were also seen between the intermediate-age groups, and data from 1976 to 1983 demonstrated identical age-related trends. CONCLUSION: Our study reveals that the probability of diagnosing cancer of the cervix, uterus and ovaries at a localized and potentially curable stage decreases with advancing age. Published national health practice patterns demonstrated a similar age-related decline in gynecologic examinations and Pap smears even after adjustment for the exclusion of women who would have undergone previous hysterectomy. This decreasing use of gynecologic examinations may in part explain the age-related decline in localized gynecologic cancers.

Splenic enlargement and Traube's space: how useful is percussion?

PURPOSE: The utility of Traube's space percussion in the bedside assessment of splenic enlargement was evaluated. The influence of meals and obesity on this sign were also assessed, because both are believed to interfere with the results of abdominal percussion. PATIENTS AND METHODS: The inpatient population of a tertiary care hospital was studied where cases and controls were selected according to the results of abdominal ultrasonographic examinations. RESULTS: Traube's space percussion exhibited a sensitivity of 0.62 (95% confidence interval [CI], 0.51 to 0.71) and a specificity of 0.72 (95% CI, 0.65 to 0.80) when classifying tympanitic examinations as negative. False-positive examinations were reduced by assessing patients more than two hours after mealtime. Obese patients were a source of false-negative examinations. CONCLUSION: Traube's space percussion compares favorably with other commonly used clinical maneuvers and diagnostic tests. When performed alone in a selected patient population, it adds useful clinical information but is not sufficiently sensitive or specific to obviate the need for further diagnostic testing.

The bedside assessment of splenic enlargement.

STUDY OBJECTIVE: To evaluate the clinical assessment of splenic enlargement using specific bedside maneuvers including Traube's space percussion, the splenic percussion sign, Middleton's maneuver, supine palpation, and right lateral decubitus palpation. DESIGN: Quasi-experimental prospective study of cases and controls selected according to the results of abdominal ultrasonographic examinations. SETTING: Selected inpatients of a tertiary care hospital. MAIN RESULTS: Comparing the areas under the receiver operating characteristic curves for each bedside maneuver demonstrated that Traube's space percussion and palpation were significant discriminators (p less than 0.001) of splenic enlargement with respective areas of 0.70 +/- 0.04 and 0.76 +/- 0.04. No one palpation maneuver was superior to another, and right lateral decubitus palpation was not useful when performed after supine palpation. The splenic percussion sign (sensitivity 79%, specificity 46%) was no better than Traube's space percussion (sensitivity 62% and specificity 72%) in assessing splenic enlargement. The palpation maneuvers appeared more sensitive and more specific than Traube's space percussion. Palpation was a significant clinical discriminator when performed on patients who exhibited percussion dullness of Traube's space (area = 0.87 +/- 0.04, p less than 0.0001) but was of little value among those without percussion dullness (area = 0.55 +/- 0.08). Also, palpation was significantly more accurate when performed on lean patients versus obese patients (areas = 0.83 +/- 0.04 versus 0.65 +/- 0.08, p less than 0.05). When a positive bedside examination was defined as positive palpation and positive percussion (concordant-positive), the combined test sensitivity and specificity were 46% and 97% respectively. CONCLUSIONS: The optimal clinical assessment of splenic enlargement includes the percussion of Traube's space. If Traube's space is dull, palpation of the spleen is warranted. This assessment is most accurate in lean patients.

Risk-benefit assessment of drug treatment to prevent coronary heart disease. Estimating the benefits of risk factor modification.

Risk factor modification to prevent the development of coronary heart disease (CHD) is a rapidly growing concern of physicians interested in disease prevention. Drug treatments to reduce hypertension and hyperlipidaemia are 2 important interventions for CHD primary prevention. The benefits of these interventions have been demonstrated in short term clinical trials by reducing the incidence of stroke and coronary events. While the short term benefits may appear modest, the long term changes in life expectancy and disease morbidity may be substantial for carefully targeted groups of patients. Computer models are therefore increasingly being used to estimate the long term benefits of risk factor modification among selected patients. A review of published CHD models demonstrates that predictions among the different models are usually consistent. Moreover, the results of randomised clinical trials can be accurately forecasted using the CHD Primary Prevention Model.

Bayesian estimation of disease prevalence and the parameters of diagnostic tests in the absence of a gold standard.

It is common in population screening surveys or in the investigation of new diagnostic tests to have results from one or more tests investigating the same condition or disease, none of which can be considered a gold standard. For example, two methods often used in population-based surveys for estimating the prevalence of a parasitic or other infection are stool examinations and serologic testing. However, it is known that results from stool examinations generally underestimate the prevalence, while serology generally results in overestimation. Using a Bayesian approach, simultaneous inferences about the population prevalence and the sensitivity, specificity, and positive and negative predictive values of each diagnostic test are possible. The methods presented here can be applied to each test separately or to two or more tests combined. Marginal posterior densities of all parameters are estimated using the Gibbs sampler. The techniques are applied to the estimation of the prevalence of Strongyloides infection and to the investigation of the diagnostic test properties of stool examinations and serologic testing, using data from a survey of all Cambodian refugees who arrived in Montreal, Canada, during an 8-month period.

Identifying adults at increased risk of coronary disease. How well do the current cholesterol guidelines work?

OBJECTIVE: To assess the accuracy of lipid screening strategies to identify individuals at increased risk of coronary heart disease mortality. PATIENTS: The 15% random sample of adults recruited into the Lipid Research Clinic Prevalence and Follow-up Studies, which included 3678 men and women aged 35 to 74 years. Total plasma cholesterol levels, lipoprotein fractions, and other coronary risk factors at study entry were compared with subsequent coronary heart disease mortality (mean follow-up, 12.2 years). MAIN OUTCOME MEASURES: The areas under receiver operating characteristic curves for blood lipids, lipid ratios, the screening guidelines proposed by the National National Cholesterol Education Program, those of the Canadian Consensus Conference on Cholesterol, and a coronary risk model that used Framingham data. MAIN RESULTS: The current National Cholesterol Education Program guidelines (area under the curve, 0.74) were significantly (P = .03) more accurate than the old National Cholesterol Education Program guidelines (area, 0.72). The ratio of total plasma cholesterol level to high-density lipoprotein cholesterol level (area, 0.72) was as accurate as current National Cholesterol Education Program guidelines. The coronary risk model (area, 0.85) was superior (P < .003) to all other screening maneuvers. Compared with the current National Cholesterol Education Program guidelines, the risk model demonstrated superior test sensitivity (70% vs 45%) with only slightly reduced specificity (82% vs 86%). CONCLUSION: The ratio of total plasma cholesterol level to high-density lipoprotein cholesterol level is as accurate as current American screening guidelines. Future guidelines should better incorporate high-density lipoprotein cholesterol levels and nonlipid risk factors to target high-risk individuals accurately.

Screening for hypercholesterolemia among Canadians: how much will it cost?

OBJECTIVE: To determine the cost of screening all Canadians aged 30 years or more without coronary heart disease (CHD) for hypercholesterolemia. DATA SOURCES: The expected results of initial screening of the serum cholesterol level were estimated on the basis of 1986 Canadian census data and the 1978 Canada Health Survey. The results of repeat testing were estimated on the basis of data from the Lipid Research Clinics Prevalence Study. Lipid profile results were extrapolated from tests at the Montreal General Hospital's clinical chemistry laboratory. Laboratory costs and primary care practitioner costs were provided by the Canadian Society of Clinical Chemists and provincial fee schedules respectively. MAIN RESULTS: Among 12,479,356 Canadians free of CHD 48.7% would be identified as being at high risk, 4.8% would be identified as being at moderate risk, and 46.6% would be reassured that their lipid risk for CHD was low. The total cost of implementing the program in the first year would be $432 million to $561 million ($325 million for laboratory tests and $107 million to $236 million for visits to primary care practitioners). CONCLUSION: The substantial cost of implementing a nationwide screening program must be weighed against the expected benefits to ensure that the final result is both practical and economically feasible.

The cost-effectiveness of exercise training for the primary and secondary prevention of cardiovascular disease.

BACKGROUND: Although exercise training improves cardiovascular disease (CVD) risk factors, few studies have evaluated its potential long-term cost-effectiveness. METHODS: Using the Cardiovascular Disease Life Expectancy Model, a validated disease simulation model, we calculated the life expectancy of average 35- to 74-year-old Canadians found in the 1992 Canadian Heart Health Survey. The impacts of exercise training on cardiovascular risk factors were estimated as a 4% decrease in low-density lipoprotein (LDL) cholesterol, a 5% increase in high-density lipoprotein (HDL) cholesterol, and a 6 mm Hg decrease in both systolic and diastolic blood pressure. Exercise adherence was estimated at 50% for the first year and 30% for all additional years. Costs for a supervised exercise program determined from Canadian sources and converted to US dollars were estimated at $605 for the first year (medical evaluation, stress test, exercise prescription, and program costs) and $367 for all additional years (program costs). For an unsupervised program, the costs were estimated at $311 for the first year and $73 for all additional years. RESULTS: The cost-effectiveness (CE) of an unsupervised exercise program (1996 U.S. dollars) was less than $12,000 per year of life saved (YOLS) for all individuals. The CE of a supervised exercise program was less than $15,000/YOLS for men with CVD, and between $12,000 and $43,000 for women with CVD and men without CVD. CONCLUSIONS: Given the relatively few risks, substantial long-term benefits, and modest costs, an unsupervised exercise training program represents good value for all. A more expensive supervised exercise program is also cost-effective for most individuals with CVD.

Economic impact of HIV infection and coronary heart disease in immigrants to Canada.

OBJECTIVE: To compare the direct health care costs of illnesses associated with the human immunodeficiency virus (HIV) and of coronary heart disease (CHD) in immigrants to Canada. DESIGN: Comparative cost analysis. PARTICIPANTS: All people who immigrated to Canada in 1988. The numbers with HIV infection and CHD were estimated from country-specific HIV seroprevalence data and national CHD mortality statistics and data from the Framingham study. Health care costs, projected over the 10 years after immigration, were calculated on the basis of data from the Hospital Medical Records Institute and provincial fee schedules. RESULTS: Of the 161,929 immigrants in 1988, 484 were estimated to be HIV positive. The total cost of treatment of HIV-related illnesses from 1989 to 1998 (discounted at 3%) would be $18.5 million: $17.1 million would be spent on the outpatient and inpatient care of the HIV-positive immigrants, $1.0 million on care of the subsequently infected sexual partners and $0.4 million on care of the HIV-positive children born to seropositive immigrant women. In comparison, CHD would develop in 2558 immigrants during the same 10-year period. The total CHD costs would be $21.6 million: $8.4 million would be spent on treating myocardial infarction, $3.2 million on coronary artery bypass grafting, $1.6 million on pacemaker insertion and $8.4 million on treating other CHD events. CONCLUSIONS: The economic impact of HIV infection in immigrants to Canada is similar to that of CHD. This comparison identifies an important shortcoming in current immigration policy: economic considerations can be arbitrarily applied to certain diseases, thereby discriminating against specific groups of immigrants.

Seizure vs. syncope: measuring serum creatine kinase in the emergency department.

OBJECTIVE: To determine the utility of serum creatine kinase measurement for diagnosing generalized tonic-clonic seizures in patients presenting to an emergency department with transient loss of consciousness. DESIGN: Prospective evaluation of a diagnostic parameter. Retrospective data collection with blinded assignment to diagnostic groups. SETTING: University teaching hospital. PATIENTS: Sequential sample of 205 patients with transient loss of consciousness. The study group consisted of 96 patients who had creatine kinase measurements in the emergency department. MEASUREMENTS AND MAIN RESULTS: An investigator blinded to the results of creatine kinase measurements retrospectively classified events into seizure and nonseizure groups on the basis of clinical presentation, prior history, and follow-up investigations. Mean (+/- SE) creatine kinase level was significantly higher in the seizure group (231.1 +/- 34.8 U/L vs. 70.5 +/- 5.6 U/L, p less than 0.001). Elevated creatine kinase had a test specificity of 0.98 (95% CI 0.90-1.00) and a sensitivity of 0.43 (95% CI 0.28-0.59). The discriminating power of creatine kinase elevation was directly related to the time interval between the event and testing (p less than 0.0001). Among samples taken more than three hours after the event, test sensitivity was 0.80 (0.52-1.00) and specificity was 0.94 (0.71-1.00). CONCLUSION: Creatine kinase may be a useful test for evaluating patients with transient loss of consciousness. The test is highly specific for diagnosing generalized seizures in the emergency department. Test sensitivity improves by sampling serum at least three hours after the event.

The cost-effectiveness of HMG-CoA reductase inhibitors to prevent coronary heart disease. Estimating the benefits of increasing HDL-C.

OBJECTIVE: To evaluate the lifetime cost-effectiveness of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors for treatment of high blood cholesterol levels. DESIGN: We added cost data to a validated coronary heart disease (CHD) prevention computer model that estimates the benefits of lifelong risk factor modification. The updated model takes into account the costs of cholesterol reduction, the savings in CHD health care costs attributable to intervention, the additional non-CHD costs resulting from patients' living longer, and the beneficial effects of reducing CHD risk by reducing total cholesterol and increasing high-density lipoprotein cholesterol (HDL-C). PATIENTS: Men and women aged 30 to 70 years who were free of CHD, had total cholesterol levels equal to the 90th percentile of the US distribution in their age and sex group, had HDL-C levels equal to the mean of the US distribution in their age and sex group, and were either with or without additional CHD risk factors. INTERVENTION: Use of 20 mg of lovastatin per day, which on average reduces total serum cholesterol by 17% and increases HDL-C by 7%. MAIN OUTCOME MEASURES: Cost per year of life saved after discounting benefits and costs by 5% annually. RESULTS: The increase in HDL-C associated with lovastatin lowered cost-effectiveness ratios by approximately 40%, such that the treatment of hypercholesterolemia was relatively cost-effective for men (as low as $20,882 per year of life saved at age 50 years) and women ($36,627 per year of life saved at age 60 years) with additional risk factors. Non-CHD costs resulting from longer life expectancy after intervention added at most 23% to the cost-effectiveness ratios for patients who began treatment at age 70 years, and as little as 3% for patients at age 30 years. CONCLUSION: The cost-effectiveness of HMG-CoA reductase inhibitors varied widely by age and sex and was sensitive to the presence of non-lipid CHD risk factors. The additional non-CHD costs due to increased life expectancy may be significant for the elderly. Accounting for the drug effects of raising HDL-C levels increased the proportion of the population for which medication treatment was relatively cost-effective.

The benefits of treating hyperlipidemia to prevent coronary heart disease. Estimating changes in life expectancy and morbidity.

OBJECTIVE: To evaluate the lifetime benefits of reducing total serum cholesterol levels to prevent coronary heart disease (CHD). DESIGN: We developed a CHD primary prevention computer model to estimate the benefits associated with lifelong risk factor modification. We validated the model by comparing the computer estimates with the observed results of three primary CHD prevention trials. PATIENTS: Men and women age 35 to 65 years who are free of CHD, with total serum cholesterol levels ranging from 5.2 to 7.8 mmol/L (200 to 300 mg/dL), with or without additional CHD risk factors. INTERVENTIONS: Serum cholesterol reduction through dietary modification or diet and medications. MAIN OUTCOME MEASURES: Changes in life expectancy and the delay of symptomatic CHD. RESULTS: The computer forecasts for CHD end points closely matched the observed results of the Lipid Research Clinics Trial, the Helsinki Heart Study, and MRFIT. We then applied the computer model to low-risk and high-risk men and women with total serum cholesterol levels between 5.2 and 7.8 mmol/L (200 and 300 mg/dL) and estimated that, after reducing serum cholesterol levels 5% to 33%, the average life expectancy would increase by 0.03 to 3.16 years. We also forecast that the average onset of symptomatic CHD would be delayed among these patient groups by 0.06 to 4.98 years. CONCLUSION: We conclude that this computer model accurately estimates the results of clinical trials and can be used to forecast the changes in life expectancy and morbidity (the development of CHD) associated with specific CHD risk reduction interventions. The wide variation surrounding these estimates underscores the need to better define which groups of individuals will gain the most from cholesterol reduction.

Impact of treating hyperlipidemia or hypertension to reduce the risk of death from coronary artery disease.

OBJECTIVE: To compare the prevalence of modifiable risk factors for cardiovascular disease among hypertensive and nonhypertensive adults and to estimate the effect of treating hyperlipidemia or hypertension to reduce the risk of death from coronary artery disease. METHODS: The authors evaluated a sample of 7814 subjects aged 35-74 years free of clinical cardiovascular disease from the Canadian Heart Health Surveys to estimate the prevalence of cardiovascular risk factors. They identified hyperlipidemic subjects (ratio of total cholesterol to high-density lipoprotein cholesterol [total-C/HDL-C] 6.0 [corrected] or more for men and 5.0 [corrected] or more for women) and hypertensive subjects (systolic or diastolic blood pressure 160/90 mm Hg or greater, or receiving pharmacologic or nonpharmacologic treatment). A life expectancy model was used to estimate the rate of death from coronary artery disease following specific treatments. RESULTS: An elevated total-C/HDL-C ratio was significantly more common among hypertensive than nonhypertensive men aged 35-64 (rate ratio [RR] 1.56 for age 35-54, 1.28 for age 55-64) and among hypertensive than nonhypertensive women of all ages (RR 2.73 for age 35-54, 1.58 for age 55-64, 1.31 for age 65-74). Obesity and a sedentary lifestyle were also more common among hypertensive than among nonhypertensive subjects. According to the model, more deaths from coronary artery disease could be prevented among subjects with treated but uncontrolled hypertension by modifying lipids rather than by further reducing blood pressure for men aged 35-54 (reduction of 50 v. 29 deaths per 100,000) and 55-64 (reduction of 171 v. 104 deaths per 100,000) and for women aged 35-54 (reduction of 44 v. 39 deaths per 100,000). Starting antihypertensive therapy in subjects aged 35-74 with untreated hypertension would achieve a greater net reduction in deaths from coronary artery disease than would lipid lowering. Nonetheless, the benefits of lipid therapy were substantial: lipid intervention among hypertensive subjects aged 35-74 represented 36% of the total benefits of treating hyperlipidemia in the total hyperlipidemic population. INTERPRETATION: The clustering of hyperlipidemia and the potential benefits of treatment among hypertensive adults demonstrate the need for screening and treating other cardiovascular risk factors beyond simply controlling blood pressure.