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Purpose: Prostate cancer aggressiveness and appropriate therapy are routinely determined following biopsy sampling. Current clinical and pathologic parameters are insufficient for accurate risk prediction leading primarily to overtreatment and also missed opportunities for curative therapy.Experimental Design: An 8-biomarker proteomic assay for intact tissue biopsies predictive of prostate pathology was defined in a study of 381 patient biopsies with matched prostatectomy specimens. A second blinded study of 276 cases validated this assay's ability to distinguish “favorable” versus “nonfavorable” pathology independently and relative to current risk classification systems National Comprehensive Cancer Network (NCCN and D'Amico).Results: A favorable biomarker risk score of ≤0.33, and a nonfavorable risk score of >0.80 (possible range between 0 and 1) were defined on “false-negative” and “false-positive” rates of 10% and 5%, respectively. At a risk score ≤0.33, predictive values for favorable pathology in very low-risk and low-risk NCCN and low-risk D'Amico groups were 95%, 81.5%, and 87.2%, respectively, higher than for these current risk classification groups themselves (80.3%, 63.8%, and 70.6%, respectively). The predictive value for nonfavorable pathology was 76.9% at biomarker risk scores >0.8 across all risk groups. Increased biomarker risk scores correlated with decreased frequency of favorable cases across all risk groups. The validation study met its two coprimary endpoints, separating favorable from nonfavorable pathology (AUC, 0.68; P < 0.0001; OR, 20.9) and GS-6 versus non–GS-6 pathology (AUC, 0.65; P < 0.0001; OR, 12.95).Conclusions: The 8-biomarker assay provided individualized, independent prognostic information relative to current risk stratification systems, and may improve the precision of clinical decision making following prostate biopsy. Clin Cancer Res; 21(11); 2591–600. ©2015 AACR.

Supplementary Methods, Table S1, Figures S1-7. Methods for quantitative multiplex proteomics imaging (QMPI) Clinical studies: Statistical plan Table S1. Clinical Validation Study. Comparison of Predictive Value of the 8-Biomarker Assay for Favorable Pathology with D'Amico Risk Categories. Figure S1. Outline of all four quantitative multiplex immunofluorescence triplex assay formats Figure S2. Clinical validation study, full cohort (N=276): performance for "GS 6" pathology (surgical Gleason =3+3 and localized {less than or equal to}T3a). A) Sensitivity (P[risk score> threshold| "non-GS 6" pathology]) of the assay, as a function of medical decision level. Figure S3. Clinical validation study, full cohort (N=274): performance for prediction of favorable pathology (surgical Gleason {less than or equal to}3+4 and organ-confined {less than or equal to}T2). Figure S4. Clinical validation study, Subset of validation cohort that contained sufficient annotation for National Comprehensive Cancer Network (NCCN) and D'Amico categorization (N=256) Figure S5. Clinical validation study: performance for prediction of favorable pathology. Figure S6. Net Reclassification Index analysis illustrates how biomarker assay categories of favorable (risk score {less than or equal to}0·33) and non-favorable (risk score >0·8) may supplement NCCN Figure S7. Decision Curve Analysis provides another method for characterizing performance of different risk systems and at different cut points.

ObjectiveTo compare clinical characteristics and treatment of patients with rheumatoid arthritis (RA) across 4 Canadian cohorts.MethodsThe 4 longitudinal cohorts included the following: the Canadian Early Arthritis Cohort (CATCH; n = 2878), Ontario Best Practices Research Initiative (OBRI; n = 3734), RHUMADATA (Quebec, n = 2890), and the Rheum4U Precision Health Registry (Calgary, Alberta, n = 709). Data were from cohort inception (range 1998–2016) to 2020. Clinical characteristics and drug treatments were summarized descriptively.ResultsIn total, 10,211 patients with RA were included. The percentage of patients who entered the cohort with early RA (2 yrs of disease at enrollment) ranged from 29% (Rheum4U) to 100% (CATCH). Mean age (55 yrs), sex (74% female), and seropositivity (69%) were similar between cohorts. At the time of initial disease-modifying antirheumatic drug (DMARD) use, median Disease Activity Score in 28 joints (DAS28) varied, ranging from 2.99 (Rheum4U) to 5.19 (CATCH), but were more similar at the time of the first DMARD switch (range 3.57–5.03), first biologic (bDMARD) or targeted synthetic DMARD (tsDMARD) use (range 4.01–4.67), and second bDMARD or tsDMARD (range 3.71–4.39). The initial DMARD was most commonly methotrexate, either in monotherapy (32%, range 18–40%) or dual therapy (34%, range 29–42%). The first DMARD switch was to another DMARD monotherapy in 20% (range 10–32%), dual therapy in 49% (range 39–56%), and bDMARD or tsDMARD in 24% (range 15–28%). The first bDMARD was an anti–tumor necrosis factor in 79% (range 78–82%).ConclusionCanadian RA cohorts demonstrate some heterogeneity in treatment, which could reflect differences in inclusion criteria, calendar year, or regional differences. This project is a first step toward conducting harmonized analyses across Canadian RA cohorts.

In our clinical experience, we have encountered patients who developed hypomagnesemia after the introduction of teriparatide. Some trials have reported hypomagnesemia as an adverse event during teriparatide treatment, but this issue had never been studied specifically. Our objective was twofold: 1) determine the incidence of hypomagnesemia (serum magnesium

Purpose: Prostate cancer aggressiveness and appropriate therapy are routinely determined following biopsy sampling. Current clinical and pathologic parameters are insufficient for accurate risk prediction leading primarily to overtreatment and also missed opportunities for curative therapy. Experimental Design: An 8-biomarker proteomic assay for intact tissue biopsies predictive of prostate pathology was defined in a study of 381 patient biopsies with matched prostatectomy specimens. A second blinded study of 276 cases validated this assay's ability to distinguish “favorable” versus “nonfavorable” pathology independently and relative to current risk classification systems National Comprehensive Cancer Network (NCCN and D'Amico). Results: A favorable biomarker risk score of ≤0.33, and a nonfavorable risk score of >0.80 (possible range between 0 and 1) were defined on “false-negative” and “false-positive” rates of 10% and 5%, respectively. At a risk score ≤0.33, predictive values for favorable pathology in very low-risk and low-risk NCCN and low-risk D'Amico groups were 95%, 81.5%, and 87.2%, respectively, higher than for these current risk classification groups themselves (80.3%, 63.8%, and 70.6%, respectively). The predictive value for nonfavorable pathology was 76.9% at biomarker risk scores >0.8 across all risk groups. Increased biomarker risk scores correlated with decreased frequency of favorable cases across all risk groups. The validation study met its two coprimary endpoints, separating favorable from nonfavorable pathology (AUC, 0.68; P < 0.0001; OR, 20.9) and GS-6 versus non–GS-6 pathology (AUC, 0.65; P < 0.0001; OR, 12.95). Conclusions: The 8-biomarker assay provided individualized, independent prognostic information relative to current risk stratification systems, and may improve the precision of clinical decision making following prostate biopsy. Clin Cancer Res; 21(11); 2591–600. ©2015 AACR.

Background The management of cardiovascular risk factors such as hypertension and dyslipidemia is poorly described in many communities, and the benefits associated with tighter control remain unknown. We used data from the 2007 MyHealthCheckup survey to document the treatment gaps and estimated the potential benefits of better adherence to recommended guidelines. Methods Cardiovascular risk factors, lifestyle habits, and prescribed medications were evaluated among Canadian adults recruited primarily in pharmacies. The Cardiovascular Life Expectancy Model was used to estimate the potential benefits of optimally treating hypertension or dyslipidemia (defined as not smoking, regular physical activity, an acceptable body weight, and maximal medication as needed). Results Among 2674 screened individuals, 1266 (47%) were receiving pharmacotherapy for either dyslipidemia or hypertension, including 772 (61%) and 656 (63%), respectively, who remained above treatment targets. Among those above lipid or blood pressure targets, 27% and 22%, respectively, were optimally treated. The average increased life expectancy or life-years gained associated with making appropriate lifestyle changes included 2.2 to 4.7 years from smoking cessation, 0.7 to 1.1 years from regular exercise, and 0.4 to 0.7 years from weight reduction. The life-years gained following better risk factor treatment included maximal pharmacotherapy for elevated blood pressure (0.6-0.8), low-density lipoprotein cholesterol (0.5-0.6), and the ratio of total cholesterol to high-density lipoprotein cholesterol (0.3-0.4). Years of life free of cardiovascular disease would be similarly increased. Conclusions Better treatment of cardiovascular risk factors could result in a substantial reduction in morbidity and mortality among Canadians. Given current physician prescribing and patient habits, lifestyle modification should be considered a priority before additional medications are prescribed.

Background and objectives The direct health care costs associated with treating hypertension and dyslipidemia continue to grow in most western countries, including Canada. Despite the proven effectiveness of hypertension and lipid therapies to prevent cardiovascular disease, the cost- effectiveness of long-term primary prevention, as currently advocated by Canadian treatment guidelines, remains to be determined. Methods Therapeutic efficiency, defined as person-years of treatment per year of life saved (YOLS) and the cost-effectiveness of treatment were estimated for groups of Canadian adults, 40 to 74 years of age. The clinical indications for treatment were based on the Canadian national guidelines in 2005. Analyses focused on those without cardiovascular disease or diabetes using risk factor data from the Canadian heart health surveys and drug data from a national study, the MyHealthCheckUp survey. The expected impact of therapy was based on published results: statins would result in a 40% drop in low-density lipoprotein cholesterol and a 6% increase in high-density lipoprotein cholesterol, while hypertension therapy would result in a 6.4% drop in systolic and a 5.6% drop in diastolic blood pressure. Results The estimated daily cost of statins was $1.98 versus $1.72 for antihypertensives. Overall, 2.33 million patients would be treated with lipid therapy and 2.34 million with antihypertensives. The average costeffectiveness of lipid therapy would be approximately $16,700 per YOLS while hypertension therapy would be approximately $37,100 per YOLS. Lifelong lipid and hypertension therapy would be associated with 1.1 million and 472,000 life years saved at a national cost of $18.3 billion and $17.5 billion, respectively. However, hypertension treatment for some groups of Canadians appeared relatively expensive (more than $50,000 per YOLS) including men or women younger than 50 years of age. Despite attractive cost-effectiveness ratios, treatment appeared relatively inefficient (person-years of treatment per YOLS more than 100 years) for statin therapy among women younger than 50 years of age, and hypertension treatment for women younger than 60 years of age and men younger than 50 years of age. Conclusions Given Canadian guidelines, the treatment of dyslipidemia or hypertension in primary prevention appears economically attractive overall. However, for some groups of individuals, the forecasted future benefits appear to be relatively small given the many years of treatment that are required.

Background Treatments for hypertension and dyslipidemia to prevent the development of cardiovascular disease compete for the same finite number of health care dollars. Therefore, the potential benefits of treating Canadians without cardiovascular disease or diabetes who would currently be targeted by the national treatment guidelines were estimated and compared. Study Design Canadian Heart Health Surveys data were used to estimate the number of Canadians requiring intervention. The Cardiovascular Life Expectancy Model , a previously validated Markov model, was used to calculate the increased life expectancy and decreased morbidity associated with treating risk factors to target. Results Among 8.44 million adults 40 to 74 years of age without cardiovascular disease or diabetes, it was estimated that approximately 2.33 million would require treatment for dyslipidemia and 2.34 million for hypertension. The estimated Framingham 10-year coronary risk averaged 12.4% versus 9.6%, respectively. Treating dyslipidemia was associated with an average increased life expectancy of 1.67 years and 1.81 years of life free of cardiovascular disease. Treating hypertension was expected to increase life expectancy by 0.94 years and years of life free of cardiovascular disease by 1.29 years. The population benefits associated with treating dyslipidemia or hypertension would be 2.5 million and 1.4 million person years of life saved, respectively. Overall, the person years of treatment required to save one year of life was estimated to average 20 years for dyslipidemia therapy and 38 years for hypertension. Conclusions The potential benefits associated with treating hypertension or dyslipidemia to prevent cardiovascular disease are substantial. However, compared with hypertension guidelines, dyslipidemia guidelines target higher-risk patients. Accordingly, given the relative efficacy of each treatment, the forecasted benefits associated with treating dyslipidemia are substantially greater than those associated with hypertension therapy.

We investigated the effect of dyslipidemia associated with highly active antiretroviral therapy on cardiovascular risk and life expectancy among patients who had the human immunodeficiency virus. Dyslipidemia estimates were based on results from a phase 2 randomized trial that compared lipid changes after 32 weeks of therapy with atazanavir with those with nelfinavir (each in combination with stavudine and lamivudine). The resultant increased coronary risk was estimated using Framingham risk equations, and change in life expectancy (after adjustment for mortality due to human immunodeficiency virus) was based on the cardiovascular life expectancy model, which is based on a published Markov's model. Levels of total cholesterol and low-density lipoprotein cholesterol increased significantly more among patients who used nelfinavir (+24% and +28%) than among those who used atazanavir (+4% and +1%). This dyslipidemia increased the risk of coronary disease by 50% over 10 years. The absence of dyslipidemia was estimated to preserve life expectancy 0.15 to 1.53 additional years depending on a patient's age, gender, and other risk factors. There are increasing reports of dyslipidemia and cardiovascular events associated with highly active antiretroviral therapy. Significant increases in blood lipid levels observed with some protease inhibitors are associated with an increase in calculated 10-year coronary risk. Accordingly, minimizing dyslipidemia associated with highly active antiretroviral therapy may preserve life expectancy among adults who have the human immunodeficiency virus.

Background. The ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol (or the ratio of low-density lipoprotein [LDL] to HDL) is currently advocated to estimate the coronary risk associated with LDL and HDL cholesterol levels. Methods. We analyzed the relation between LDL and HDL cholesterol levels to predict the risk of future coronary events. Using data from the Lipid Research Clinics Follow-up Cohort, we developed multivariate equations to predict coronary deaths among 4684 men and women followed for approximately 12 years. We used these equations to compare the predictive power of the LDL/HDL ratio with the independent effects of LDL and HDL and an LDL-HDL interaction term. We then used each model to forecast the 10-year risk of coronary death based on various lipid levels after adjustment for conventional risk factors (eg, blood pressure, gender, cigarette smoking). Results. Levels of LDL and HDL and the interaction between them are all independent risk factors for coronary death. The benefits of increasing HDL are strongest among persons with high LDL. Conversely, the benefits of decreasing LDL are greatest among those with low HDL. We confirmed these observations in a published dataset showing the effects of treatment of hyperlipidemia. Predictions of benefits of treatment that were based on interaction of LDL and HDL were more accurate than predictions without interaction. Conclusions. The LDL/HDL ratio alone may not fully capture the complex interaction between LDL and HDL and the relation of each to coronary risk. (EPIDEMIOLOGY 2003;14:315–320)

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.

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.

To evaluate the nursing care needs of patients admitted to the hospital for complications of AIDS, we compared the estimated nursing care requirements of AIDS patients with non-AIDS patients at the...

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.

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

There is little debate that preventing the complications of cardiovascular disease is worthwhile. Advancing clinical knowledge supported by the positive results of clinical trials continues to expand the indications for preventive therapy. Unfortunately, the growing number of therapeutic successes comes at a cost that many health care providers can no longer afford. Accordingly, health economic analyses have become an essential component of contemporary health policy. Cost-effectiveness analyses are now commonplace as health care decision makers attempt to allocate limited resources to those interventions that provide the best value for the money. However, comparisons between studies are often difficult. Common problems include different patient populations in which the underlying risk of cardiovascular events can vary widely, inconsistent patient adherence to prescribed therapy and the variable duration of clinical trials. Study duration may be particularly important, given that most preventive therapies are prescribed for a lifetime, while almost all clinical trials are restricted to a time horizon that rarely exceeds five years. Accordingly, the uncertainty surrounding drug efficacy beyond the duration of a specific clinical trial remains a major challenge for health care analysts. The 33rd Bethesda Conference in 2002 (1), sponsored by the American College of Cardiology, focused on preventive interventions. The working group that reviewed the cost-effectiveness of prevention recognized the importance of the time horizon in economic analyses. Among the published studies of hypertension or lipid-lowering therapy that were reviewed, the analyzed time horizon ranged from five years to a lifetime. As a general rule, reported cost-effectiveness ratios tended to be lower over longer periods of therapy. To date, there has not been a systematic evaluation of the importance of the time horizon as a major determinant of both the costs and benefits of treatment. When focusing on one specific drug, cost-effectiveness estimates can also vary widely, as demonstrated by the range of results published for ramipril (2–10). Ramipril is an angiotensin-converting enzyme inhibitor that has been shown to reduce the risk of fatal and nonfatal cardiovascular events in a number of patient populations. In the Heart Outcomes Prevention Evaluation (HOPE) study (11), ramipril was shown to reduce the rates of death, myocardial infarction and stroke among individuals with cardiovascular disease, or diabetes plus one other cardiovascular risk factor. When data analysis was restricted to those individuals with diabetes (Microalbuminuria, Cardiovascular, and Renal Outcomes [MICRO-HOPE]) (12), treatment reduced the risk of myocardial infarction, stroke, cardiovascular death and total mortality. In the Acute Infarction Ramipril Efficacy (AIRE) study (13), individuals with clinical evidence of heart failure at any time after acute myocardial infarction were also shown to benefit from ramipril, as evidenced by a reduction in cardiovascular events and total mortality. In the first two studies, treatment duration was 4.5 years, while participants in AIRE were followed for approximately 15 months. To evaluate the importance of the time horizon in economic analyses, the cost-effectiveness of ramipril was compared in these three studies. Initially, the actual study duration was used to estimate the cost-effectiveness of therapy during the clinical trial. A second analysis considered the costs and benefits of lifelong treatment for participants beyond the duration of each trial. A third scenario was also considered, in which it was assumed that treatment continued for the participant’s lifetime, but the benefits observed during the trial stopped at the end of the study.

Economic analyses of drug therapies are highly dependent on the clinical indications for treatment. The cost effectiveness of ramipril has been evaluated in numerous studies, usually based on the results of one specific clinical trial. We estimated the cost effectiveness of this drug across a range of currently accepted therapeutic indications, using a single health economic model and adjusted for quality of life, to compare the different outcomes observed in four clinical trials.The cardiovascular life expectancy model, a validated Markov model, was calibrated to accurately forecast the results of four trials including AIRE, HOPE, Micro-HOPE, and REIN. We then extrapolated these results over the remaining life expectancy of the patients enrolled in each study and adjusted for the quality of life associated with the observed outcomes. The cost per quality-adjusted life-year (QALY) was then calculated from the perspective of the Canadian healthcare system incorporating the estimated direct healthcare costs associated with treatments and outcomes.After discounting all costs and outcomes 3% annually, the benefits associated with ramipril ranged from 0.74 QALYs in the AIRE study to 1.22 QALYs in Micro-HOPE. Treatment was estimated to be cost-saving for some patient groups, such as those in REIN. The highest cost-effectiveness ratio was observed among individuals enrolled in HOPE ($Can20 000 per QALY in 2002).Treatment with ramipril appears to be economically attractive across a wide range of patient groups, including those with increased coronary risk and/or diabetes mellitus (HOPE and Micro-HOPE), those with congestive heart failure (AIRE), and those with non-diabetic nephropathy (REIN).

Hypertension is common among patients with dyslipidemia but is often poorly treated. The objective of this analysis was to evaluate how a decision aid, used by primary care physicians to improve lipid therapy, impacted on the treatment of hypertension.Data were analyzed from patients enrolled in a randomized trial focusing primarily on the treatment of dyslipidemia. Patients received usual care or a coronary risk profile every three months to monitor the risk reduction following lifestyle changes and/or pharmacotherapy to treat dyslipidemia. Hypertension management was assessed based on a post hoc analysis of individuals whose blood pressure exceeded current national hypertension guidelines.There were 2,631 subjects who completed the study. Among 1,352 patients without diagnosed hypertension, 30% were above target on at least three consecutive visits. Among 1,279 individuals with known hypertension, 69% were above target on at least two consecutive visits. Overall, patients receiving risk profiles were more likely to receive appropriate antihypertensive therapy (OR = 1.40, 95% CI 1.11-1.78) compared to those receiving usual care. After adjustment for inter-physician variability and potential confounders, the use of the risk profile was associated with an increased likelihood of starting therapy (OR = 1.78, 95% CI 1.06-3.00) or modifying therapy (OR = 1.40, 95% CI 1.03-1.91).In this clinical trial of dyslipidemia management, inadequately controlled hypertension was common, occurring in nearly 50% of individuals. Ongoing coronary risk assessment was associated with more appropriate blood pressure management. Cardiovascular risk assessment decision aids should be further evaluated in a randomized trial of hypertension therapy.

Recent studies suggest that the benefit of lipid-lowering treatment for the primary and secondary prevention of cardiovascular disease (CVD) extends to individuals with average cholesterol levels, to women and to the elderly. However, the proportion of the general population for which treatment is cost-effective has not been evaluated.Using data provided by the Canadian Heart Health Survey, the level of CVD risk was estimated for a random sample of the total population. A cost-effectiveness ratio for simvastatin was then calculated for each individual in the sample. Lastly, the proportion of the total population for which lipid-lowering therapy would be cost-effective for primary and secondary prevention of CVD was estimated according to total cholesterol (TC) levels.Among the surveyed individuals who were 30 to 74 years of age, 2212 had CVD and 12,982 did not. Among those with a TC level higher than 6.2 mmol/L, the proportions of individuals for which lipid-lowering therapy was cost-effective (at a level of less than 50,000 dollars per year of life saved) were 85.6% of men and 28.7% of women for primary prevention, and 99.8% of men and 86.1% of women for secondary prevention. The estimated cost of one year of lipid-lowering treatment for all individuals in the population with a TC level higher than 6.2 mmol/L and for all individuals regardless of TC levels for whom treatment would be cost-effective was $1 billion and 3.9 billion dollars, respectively.Lipid-lowering treatment for CVD prevention is cost-effective for a high proportion of the population, even for primary prevention. As a result, the cost of population-wide treatment for only one year is high even among individuals with a TC level higher than 6.2 mmol/L. Such costs should be considered in health care policy decisions.

The Prostate Cancer Prevention Trial demonstrated that finasteride could reduce the incidence of prostate cancer by 25%. However, its use was also associated with an increased risk of high grade cancer resulting in uncertainty surrounding the net benefits of therapy.We used the Montreal Prostate Cancer Model, a validated Markov model of prostate cancer progression, to compare the forecasted survival in treated and untreated men. The conditions of the model were varied to reflect different assumptions about whether the cancer grade difference observed in the PCPT was real or a treatment associated artifact, and whether cancers detected on end of study biopsies were clinically significant.For a hypothetical cohort of 1,000, 62-year-old men treated with finasteride, an increased survival of 140 life-years (0.14 years per individual) is forecasted if all diagnosed cancers are considered. If tumor grade differences are held to be artifactual, the forecasted benefits increase to 200 life-years. However, if the tumor grade difference is real and only clinically detected cancers are considered, estimated increased survival is only 20 life-years (0.02 years per individual).The primary prevention of prostate cancer with finasteride looks promising. However, at the present time it should only be considered with caution until we have answered critical questions surrounding the difference in cancer grade observed in the PCPT and the clinical significance of cancers detected on protocol directed end of study biopsies.

Osteoarthritis and hypertension are highly prevalent among older Americans. Anti-inflammatory medications can destabilize blood pressure control. We estimated the decreased cardiovascular risk, premature mortality, and direct health care costs that could be avoided if blood pressure control is not destabilized among hypertensive Americans taking cyclooxygenase-2 (COX-2)–specific inhibitors for osteoarthritis. Data from the Third National Health and Nutrition Examination Survey (NHANES III) provided the distribution of cardiovascular risk factors among American adults with osteoarthritis and hypertension. The Cardiovascular Disease Life Expectancy Model was used to estimate the impact of a 2.26% increase in systolic blood pressure on the basis of results of a randomized trial comparing COX-2–specific inhibitors. A similar analysis was completed for American adults with osteoarthritis and untreated hypertension (≥140/90 mm Hg). Among 7.3 million Americans with treated hypertension, maintaining blood pressure control would avoid >30 000 stroke deaths and 25 000 coronary deaths resulting in >449 000 person years of life saved and $1.4 billion in direct health care cost savings. When an additional 3.8 million Americans with untreated hypertension are considered, maintaining blood pressure control could prevent >47 000 stroke deaths, 39 000 coronary deaths, and result in 668 000 person years of life saved and >$2.4 billion in direct health care cost savings. We conclude that even a small increase in systolic blood pressure among hypertensive Americans with osteoarthritis may substantially increase the clinical and economic burden of cardiovascular disease. Maintaining blood pressure control may be associated with substantial benefits.

We investigated the effect of dyslipidemia associated with highly active antiretroviral therapy on cardiovascular risk and life expectancy among patients who had the human immunodeficiency virus. Dyslipidemia estimates were based on results from a phase 2 randomized trial that compared lipid changes after 32 weeks of therapy with atazanavir with those with nelfinavir (each in combination with stavudine and lamivudine). The resultant increased coronary risk was estimated using Framingham risk equations, and change in life expectancy (after adjustment for mortality due to human immunodeficiency virus) was based on the cardiovascular life expectancy model, which is based on a published Markov's model. Levels of total cholesterol and low-density lipoprotein cholesterol increased significantly more among patients who used nelfinavir (+24% and +28%) than among those who used atazanavir (+4% and +1%). This dyslipidemia increased the risk of coronary disease by 50% over 10 years. The absence of dyslipidemia was estimated to preserve life expectancy 0.15 to 1.53 additional years depending on a patient's age, gender, and other risk factors. There are increasing reports of dyslipidemia and cardiovascular events associated with highly active antiretroviral therapy. Significant increases in blood lipid levels observed with some protease inhibitors are associated with an increase in calculated 10-year coronary risk. Accordingly, minimizing dyslipidemia associated with highly active antiretroviral therapy may preserve life expectancy among adults who have the human immunodeficiency virus.

Purpose Diabetes mellitus is associated with an increased risk of cardiovascular disease. We compared the clinical effects of treating dyslipidemia in patients who had diabetes mellitus but no diagnosed cardiovascular disease with the effects of similar treatment in patients who had cardiovascular disease but no diabetes mellitus. Methods We estimated the number of adults (ages 30 to 74 years) requiring lipid therapy using data from the third National Health and Nutrition Examination Survey and current lipid treatment guidelines. Using the Cardiovascular Life Expectancy Model, we estimated the mean increase in life expectancy that would result from lowering low-density lipoprotein cholesterol levels by 35% and increasing high-density lipoprotein cholesterol levels by 8% based on results from the Scandinavian Simvastatin Survival Study. Results The mean number of years of life saved ranged from 3 to 3.4 years for men with diabetes versus 2.4 to 2.7 years for men with cardiovascular disease. In women, the estimated benefits were 1.6 to 2.4 years for those with diabetes versus 1.6 to 2.1 years for those with cardiovascular disease. Total population benefits were also substantial for patients with diabetes (25.4 million person-years of life saved) and those with cardiovascular disease (16.0 million person-years of life saved). Conclusion The clinical benefits of treating dyslipidemia in patients with diabetes should be at least equivalent to, if not more substantial than, the benefits observed among those with cardiovascular disease.

To determine whether statins are underprescribed in the Canadian military. The cost effectiveness of statin therapy in patients identified by the 1998 Canadian cholesterol interim guidelines was also explored.Charts of 1424 Canadian military personnel (age 45 or older) were reviewed at 11 Canadian bases. Risk factors and cholesterol values were used to identify drug therapy candidates. Cost effectiveness ratios and health benefits in terms of years of life saved for statin therapy were estimated for the candidates using a validated cardiovascular disease life expectancy model.Of the 1313 personnel not on lipid lowering medication, 172 were identified as drug therapy candidates. An average of 2.89 years of life saved was forecast for the identified personnel, at an average cost of less than 10,000 dollars per year of life saved.The health benefits of statin therapy in this population are substantial and the cost effectiveness is acceptable. Statin therapy warrants greater attention as a preventive strategy for coronary artery disease.

5090 Background: Current clinical and pathological parameters are insufficient for accurate prediction of progression risk for patients with biopsy Gleason grades 3+3 or 3+4. Reasons for this inclu...

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.

Objective: To forecast the long-term benefits and costeffectiveness 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 longterm 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 $13 747 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 h as n o e ffect o n t he r isk o f s troke, c osteffectiveness 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.

We thank Dr. Egede (1) for his letter in this issue of Diabetes Care and for taking the time to read our study (2) and provide us with his thoughtful comments. He raises several important points. The first point concerns the choice of years of life saved rather than quality-adjusted life years in the cost-effectiveness analysis. Dr. Egede’s point that both diabetes and cardiovascular disease may have a significant impact on quality of life is well taken. We agree with him that it would be desirable to include quality-of-life issues in …

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 (≈$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.

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.Quasi-experimental prospective study of cases and controls selected according to the results of abdominal ultrasonographic examinations.Selected inpatients of a tertiary care hospital.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.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.

Background Despite increasing evidence that treating dyslipidemia reduces cardiovascular events, many patients do not achieve recommended lipid targets. Methods To determine whether showing physicians and patients the patient's calculated coronary risk can improve the effectiveness of treating dyslipidemia in a primary care setting, patients were randomized to receive usual care or ongoing feedback regarding their calculated coronary risk and the change in this risk after lifestyle changes, pharmacotherapy, or both to treat dyslipidemia. Outcomes, based on intention-to-treat analysis, included changes in blood lipid levels, coronary risk, and the frequency of reaching lipid targets. Results Two hundred thirty primary care physicians enrolled 3053 patients. After 12 months of follow-up, 2687 patients (88.0%) remained in the study. After adjustment for baseline lipid values, significantly greater mean reductions in low-density lipoprotein cholesterol levels and the total cholesterol to high-density lipoprotein cholesterol ratio were observed in patients receiving risk profiles (51.2 mg/dL [to convert to millimoles per liter, multiply by 0.0259] and 1.5, respectively) vs usual care (48.0 mg/dL and 1.3, respectively), but the differences were small (−3.3 mg/dL; 95% confidence interval [CI], −5.4 to −1.1 mg/dL; and −0.1; 95% CI, −0.2 to −0.1, respectively). Patients in the risk profile group were also more likely to reach lipid targets (odds ratio, 1.26; 95% CI, 1.07 to 1.48). A significant dose-response effect was also noted when the impact of the risk profile was stronger in those with worse profiles. Conclusions Discussing coronary risk with the patient is associated with a small but measurable improvement in the efficacy of lipid therapy. The value of incorporating risk assessment in preventive care should be further evaluated.

The prevalence of erectile dysfunction (ED) and associated risk factors has been described in many clinical settings, but there is little information regarding men seen by primary care physicians. We sought to identify independent factors associated with ED in a primary care setting.We surveyed a cross-sectional sample of 3921 Canadian men, aged 40 to 88 years, seen by primary care physicians. Participants completed a full medical history, physical examination, and measurement of fasting blood glucose and lipid levels. We used the International Index of Erectile Function to define ED as a score of less than 26 on the erectile function domain.The overall prevalence of ED was 49.4%. The presence of cardiovascular disease (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.16-1.81; P.01) or diabetes (OR, 3.13; 95% CI, 2.35-4.16; P.001) increased the probability of ED after adjustment for other confounders. Among those individuals without cardiovascular disease or diabetes, the calculated 10-year Framingham coronary risk (OR, 1.03 per 1% increase; 95% CI, 1.02-1.05; P.001) and fasting blood glucose levels (OR, 1.14 per 18-mg/dL [1-mmol/L] increase; 95% CI, 1.04-1.24; P.01) were independently associated with ED. Erectile dysfunction was also independently associated with undiagnosed hyperglycemia (OR, 1.46; 95% CI, 1.02-2.10; P = .04), impaired fasting glucose (OR, 1.26; 95% CI, 1.08-1.46; P = .004), and the metabolic syndrome (OR, 1.45; 95% CI, 1.24-1.69; P.001).Cardiovascular disease, diabetes, future coronary risk, and increasing fasting glucose levels are independently associated with ED. It remains to be determined if ED precedes the development of these conditions.

Background: The losses in productivity due to cardiovascular disease (CVD) are substantial but rarely considered in health economic analyses. We compared the costeffectiveness of lipid level modification in the primary prevention of CVD with and without these indirect costs. Methods: We used the Cardiovascular Life Expectancy Model to estimate the long-term benefits and costeffectiveness of lipid level modification with atorvastatin calcium, including 28% and 38% reductions in total cholesterol and low-density lipoprotein cholesterol levels, respectively, and a 5.5% increase in high-density lipoprotein cholesterol level. The direct costs included all medical care costs associated with CVD. The indirect costs represented the loss of employment income and the decreased value of housekeeping services after different manifestations of CVD. All costs were expressed in 2000 Canadian dollars. Results: When only direct medical care costs were considered, the incremental cost-effectiveness ratios for lifelong therapy with atorvastatin calcium, 10 mg/d, were generally positive, ranging from a few thousand to nearly $20000 per year of life saved. When the societal point of view was adopted and indirect costs were included, the total costs were generally negative, representing substantial cost savings (up to $50000) and increased life expectancy for most groups of individuals. Conclusions: Lipid therapy with statins can reduce CVD morbidity and mortality as demonstrated in a number of clinical trials. Adding the indirect CVD costs associated with productivity losses at work and home can result in forecasted cost savings to society as a whole such that lipid therapy could potentially save lives and money. Arch Intern Med. 2003;163:333-339

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 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 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. ( JAMA . 1995;274:801-806)

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. (JAMA. 1995;273:1032-1038)

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. (Arch Intern Med. 1994;154:1697-1704)

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 characteristic 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 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. (Arch Intern Med. 1994;154:679-684)

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. (JAMA. 1992;267:816-822)

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 falsenegative 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.

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 sigificant inverse relationship between the relative proportion of tumors that were diagnosied 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.