Comparison between Medgem and Deltatrac resting metabolic rate measurements.

OBJECTIVE: The primary aims of this trial were to evaluate the reproducibility of a portable handheld calorimeter (Medgem) in a clinical population, and to compare its measures with a calorimeter in typical use with these patients. DESIGN: Cross-sectional clinical validation study. SETTING: Outpatient Clinical Research Center. SUBJECTS: A total of 24 stable home nutrition support patients. INTERVENTIONS: In random order three measures of resting metabolic rate (RMR) were taken after a 4-h fast, 15 min rest and 2-h abstention from exercise. Two measures were taken with the same Medgem (MG) and one with the traditional calorimeter (Deltatrac). Reproducibility of MG measures and their comparability to a Deltatrac measure were assessed by Bland-Altman analysis, with >+/-250 kcal/day established a priori as a clinically unacceptable error. In addition, disagreement between the two types of measures was defined as greater than 10% difference. RESULTS: The mean difference between two MG measures was -6.8 kcal/day, with limits of agreement between 233 and -247 kcal/day and clinically acceptable. The mean difference between the Deltatrac and mean of two MG measures was -162 kcal/day, with limits of agreement between 577 and -253 kcal/day and clinically unacceptable. In all, 80% of the repeated MG RMR measures agreed within 10%, and the mean MG reading agreed with the Deltatrac in 60% of cases. CONCLUSIONS: RMR obtained using the MG calorimeter has an acceptable degree of reproducibility, and is acceptable to patients. The MG measures, however, are frequently lower than traditional measures and require further validation prior to application to practice in this vulnerable patient group.

Revised estimates of diagnostic test sensitivity and specificity in suspected biliary tract disease.

BACKGROUND: The purpose of this study was to estimate the sensitivity and specificity of diagnostic tests for gallstones and acute cholecystitis. METHODS: All English-language articles published from 1966 through 1992 about tests used in the diagnosis of biliary tract disease were identified through MEDLINE. From 1614 titles, 666 abstracts were examined and 322 articles were read to identify 61 articles with information about sensitivity and specificity. Application of exclusion criteria based on clinical and methodologic criteria left 30 articles for analysis. Cluster-sampling methods were adapted to obtain combined estimates of sensitivities and specificities. Adjustments were made to estimates that were biased because the gold standard was applied preferentially to patients with positive test results. RESULTS: Ultrasound has the best unadjusted sensitivity (0.97; 95% confidence interval, 0.95 to 0.99) and specificity (0.95; 95% confidence interval, 0.88 to 1.00) for evaluating patients with suspected gallstones. Adjusted values are 0.84 (0.76 to 0.92) and 0.99 (0.97 to 1.00), respectively. Adjusted and unadjusted results for oral cholecystogram were lower. Radionuclide scanning has the best sensitivity (0.97; 95% confidence interval, 0.96 to 0.98) and specificity (0.90; 95% confidence interval, 0.86 to 0.95) for evaluating patients with suspected acute cholecystitis; test performance is unaffected by delayed imaging. Unadjusted sensitivity and specificity of ultrasound in evaluating patients with suspected acute cholecystitis are 0.94 (0.92 to 0.96) and 0.78 (0.61 to 0.96); adjusted values are 0.88 (0.74 to 1.00) and 0.80 (0.62 to 0.98). CONCLUSIONS: Ultrasound is superior to oral cholecystogram for diagnosing cholelithiasis, and radionuclide scanning is the test of choice for acute cholecystitis. However, sensitivities and specificities are somewhat lower than commonly reported. We recommend estimates that are midway between the adjusted and unadjusted values.

Hypocholesterolemic effects of a dietary fiber supplement.

The cholesterol-lowering effects of a fiber supplement were evaluated in patients with mild to moderate hypercholesterolemia. After a 9-wk diet stabilization period, patients were randomly assigned to treatment with 10 or 20 g/d of the fiber supplement or with a matching placebo. Among patients who completed the 15-wk treatment period, total cholesterol, LDL cholesterol, and the ratio of LDL to HDL (LDL/HDL) were significantly reduced (P < 0.05) for the 10- (n = 40) and 20-g/d (n = 39) groups compared with the placebo group (n = 48). In the placebo group and 10- and 20-g/d groups, the percent changes in total cholesterol were 0.4%, -5.8%, and -4.9%, in LDL cholesterol were -0.4%, -8.1%, and -7.3%, and in LDL/HDL were 1.0%, -5.6%, and -8.7%, respectively. The fiber supplement had no significant effects (P > 0.05) on HDL cholesterol or triglycerides. The changes in lipoprotein concentrations could not be attributed to changes in diet or body weight because there were no significant changes in these variables during the 15-wk treatment period.

Long-term treatment of hypercholesterolemia with dietary fiber.

PURPOSE: To evaluate the hypocholesterolemic effects of long-term treatment (36 to 51 weeks) with a mixture of dietary fibers (guar gum, pectin, soy, pea, corn bran) administered twice a day. PATIENTS AND METHODS: Fifty-nine subjects with moderate hypercholesterolemia who completed a 15-week, placebo-controlled study with the dietary fiber were treated for an additional 36 weeks with 20 g/day of fiber. Subjects were counseled and monitored on a National Cholesterol Education Program (NCEP) Step-One Diet before starting and during treatment. Analyses of changes in lipoprotein values during the additional 36 weeks of treatment took into account changes in weight, diet, and other variables that might have affected the response to treatment. RESULTS: There were no significant effects on the levels of either triglycerides or high-density lipoprotein cholesterol (HDL-C). Levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) and the LDL/HDL ratio were significantly reduced during treatment. The mean percentage reductions from baseline after 51 weeks of treatment were approximately 5% for TC, 9% for LDL-C, and 11% for the LDL/HDL ratio. Changes were apparent after 3 weeks of treatment, with the maximum reductions occurring by the 15th week of treatment. CONCLUSIONS: For subjects on a Step-One Diet who complied with the treatment regimen, the moderate cholesterol-lowering effects of the fiber persisted throughout the 36-to-51 week treatment period.

Predicting 10-year care requirements for older people with suspected Alzheimer's disease.

OBJECTIVE: To describe the types and costs of care received for 10 years after the identification of an older person with suspected Alzheimer's disease (AD) by using data from 3254 patients with suspected AD who participated in the National Long Term Care Survey (NLTCS). METHODS: By using a Markov model derived using grade of membership techniques, the following were determined: survival probabilities at 10 years; years of survival during the 10 years; years in institutions; years with two or more impairments in basic activities of daily living; hours of paid and informal care while the older person lived in the community; and costs of paid community, institutional, and medical care. RESULTS: Greater degrees of cognitive impairment present when AD was identified were associated with reduced predicted probability of surviving 10 years, increased predicted number of years spent in institutions, increased hours of care required while affected individuals remained in the community, and increased costs of paid community, institutional, and medical care. Substantial differences between men and women were seen: severity-adjusted 10-year costs were almost two times higher for women with AD than for men ($75,000 compared with $44,000); according to sensitivity analysis, average 10-year costs might be as high as $109,000 for women and $67,000 for men. CONCLUSIONS: AD imposes a substantial burden on older persons. Interventions that slow the progression of the disease may therefore affect community survival as well as healthcare costs.

The involvement of physicians in VA home care: results from a national survey.

OBJECTIVES: To examine the role of physicians in the Veteran Affairs (VA) home-based primary care (HBPC) program and to identify variables that predict whether physicians make home visits and volume of home visits made. DESIGN: Descriptive and regression analyses of responses from a mail survey. PARTICIPANTS: Forty-five physicians affiliated with VA HBPC programs. MAIN SURVEY TOPICS: Self-reported work load, attitudes toward home care, reasons for home visits, administrative policies regarding physicians' role in patient care management, and time commitment to home care. RESULTS: A majority of physicians believed strongly in the importance of home care and made home visits for reasons consistent with their training. Physician attitude toward home care and preoccupation with office or hospital practice were related to whether or not physicians made home visits. Degree of preoccupation with office practice and amount of salary support from VA HBPC were significant predictors of the number of visits made (R2 = 0.44). CONCLUSIONS: These findings indicate that most physicians will make home visits if they believe that home care is valuable and if their time commitment is supported financially. Managed care plans that own and operate home care programs and have the capacity to transfer primary care management to physicians who derive financial support from the programs should find this information particularly relevant.

The cost and cardioprotective effects of enalapril in hypertensive patients with left ventricular dysfunction.

This study examined the effect of enalapril on survival, resource use, and cost of care in patients with left ventricular dysfunction and hypertension using a retrospective analysis of patients who participated in the Studies of Left Ventricular Dysfunction (SOLVD). Among the 6797 SOLVD participants, 1917 patients had either elevated systolic (> or = 140 mm Hg) or diastolic (> or = 90 mm Hg) blood pressure. Therapy with enalapril was associated with a significant relative risk reduction for mortality (RR = 0.819, 95% CI: 0.68 to 0.98; P = .03). This resulted in a gain of 0.11 years (95% CI: 0.00 to 0.20 years) of survival during the average 2.8 year follow-up for this subgroup and was projected to result in a gain of 2.14 years (95% CI: 0.05 to 4.21 years) during the patient's lifetime. Enalapril significantly reduced the risk of first hospitalization for heart failure by 37%. For all types of hospitalizations, there was an average reduction of 32 hospitalizations per 100 patients treated with enalapril during the trial period (95% CI: 11.8 to 52.2 hospitalizations avoided per 100 patients), resulting in an estimated net savings of $1656 per patient during the trial period (95% CI: increased cost of $191 to savings of $3502). Although the projected lifetime net savings of $1456 was not significant (95% CI: increased cost of $9243 to saving of $12,527), evaluation of the cost per life year saved indicated that enalapril represented a cost-effective strategy. The estimated clinical benefit of enalapril among the hypertensive subgroup in SOLVD supports the recommendation that angiotensin converting enzyme (ACE) inhibitors should be considered as first line pharmacologic therapy for hypertensive patients with left ventricular dysfunction. From both the clinical and economic viewpoints, ACE inhibitors provide important clinical benefits and are cost-effective.

The economic impact of infections. An analysis of hospital costs and charges in surgical patients with cancer.

We performed an economic analysis of the care provided to patients undergoing major abdominal surgical procedures to determine the effect of postoperative infection on hospital resource use. Patients' clinical and demographic characteristics and their use of medical care services were determined from a review of hospital bills and medical records. Hospital charges were obtained from the hospital billing system and costs were determined by use of Medicare cost-charge ratios obtained from the hospital's Medicare Cost Report. The care of patients with postoperative infections was significantly more expensive than that of uninfected patients (multivariate analysis indicated that a surgical infection added $12,542 to the cost of patient care). Patients with postoperative fever but without documented infection were also more expensive to care for than afebrile, uninfected patients (fever added $9145 to the cost of care). Increased costs for infected patients were found among microbiology tests, radiology services, pharmaceutical costs, and room costs. For these patients, we found that use of departmental cost-charge ratios, instead of hospital-wide cost-charge ratios, had no substantial impact on comparison of the cost of care for infected and uninfected patients.

Principles of effectiveness trials and their implementation in VA Cooperative Study #430: 'Reducing the efficacy-effectiveness gap in bipolar disorder'.

Despite the availability of efficacious treatments for bipolar disorder, their effectiveness in general clinical practice is greatly attenuated, resulting in what has been called an 'efficacy-effectiveness gap'. In designing VA Cooperative Studies Program (CSP) Study #430 to address this gap, nine principles for conducting an effectiveness (in contrast to an efficacy) study were identified. These principles are presented and discussed, with specific aspects of CSP #430 serving as illustrations of how they can be implemented in an actual study. CSP #430 hypothesizes that an integrated, clinic-based treatment delivery system that emphasizes (1) algorithm-driven somatotherapy, (2) standardized patient education, and (3) easy access to a single primary mental health care provider to maximize continuity-of-care, will address the efficacy-effectiveness gap and improve disease, functional, and economic outcome. It is an 11-site, randomized controlled clinical trial of this multi-modal, clinic-based intervention versus usual VA care running from 1997 to 2003. The trial has enrolled 191 subjects in each arm, using minimal exclusion criteria to maximize the external validity of the study. Subjects are followed for 3 years. The intervention is highly specified in a series of operations manuals for each of the three components. Several continuous quality improvement (CQI) interventions, process measures, and statistical techniques deal with drift of care in both the intervention and usual care arms to ensure the internal validity of the study. CSP #430 is designed to have impact well beyond the VA, since it evaluates a basic health care operational principle: that augmenting ambulatory access for major mental illness will improve outcome and reduce overall treatment costs. If results are positive, this study will provide a reason to reconsider the prevailing trend toward limitation of ambulatory services that is characteristic of many managed care systems today.

Cholesterol and coronary heart disease: predicting risks in men by changes in levels and ratios.

BACKGROUND: Little is known about the relative ability of different measures of change in cholesterol to discriminate coronary heart disease risk. We evaluated this ability for changes in low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, LDL/HDL ratios, and total cholesterol/HDL ratios. METHODS: We predicted risks of coronary heart disease using data from 3641 men in the Lipid Research Clinics Coronary Primary Prevention Trial. Treating these patients as a cohort, we estimated risks associated with changes in cholesterol levels independent of the patients' randomization group. RESULTS: Changes in LDL and HDL cholesterol when used in combination were each significant predictors of coronary heart disease risk (odds ratios [OR] for 10% increases, 1.15 and 0.84, respectively; P < 0.001). Changes in LDL/HDL and total cholesterol/HDL ratios had similar discriminating ability (OR for 10% increases, 1.17 and 1.21, respectively; P < 0.0001). In the best discriminating models, changes in ratios added information about risks to changes in LDL cholesterol, although changes in LDL cholesterol levels failed to add information to changes in ratios. CONCLUSIONS: Changes in total cholesterol/HDL and LDL/HDL ratios were better predictors of risk for coronary heart disease than were changes in LDL cholesterol levels alone. When assessed as percentage changes averaged during the first two months of intervention, they were among the best discriminators of risk. Clinicians selecting treatments for intervention should include among their considerations the treatment's effect on both LDL and HDL cholesterol rather than their effects on LDL cholesterol levels alone.

Hyperhomocysteinemia is associated with venous thrombosis in patients with short bowel syndrome.

BACKGROUND: Hyperhomocysteinemia is associated with venous thrombosis and vitamin deficiency. Patients with short bowel syndrome have increased risk of venous thrombosis due to central catheters, and of vitamin deficiency due to malabsorption. The current investigation was designed to evaluate the relationship between history of venous thrombosis and current hyperhomocystinemia and vitamin deficiency in patients with short bowel syndrome. METHODS: Plasma total homocysteine (tHcy), serum vitamin B12, folate, B6, and methylmalonic acid (MMA) were measured. Venous thrombosis was documented by venogram or ultrasound. RESULTS: Ten of 17 patients had venous thromboses, including 17 of 38 observed superior and 12 of 26 inferior veins. Total homocysteine was correlated with number of thromboses. The relative risk of multiple thromboses in the highest tHcy tertile was 3.6-fold that of the lowest tertile. Vitamin B12 and folate levels were within normal limits, but B12 deficiency by MMA or tHcy level was apparent in 7 patients. Vitamin-deficient patients had higher tHcy and MMA than those without deficiency. CONCLUSIONS: Venous thrombosis in patients with short bowel syndrome is related to hyperhomocystinemia, which is also related to vitamin B12 deficiency, not detected by serum vitamin B12 concentration. Whether treatment of vitamin deficiencies and associated reduction in tHcy will reduce recurrent venous thrombosis in these patients is not known.

Does perioperative total parenteral nutrition reduce medical care costs?

An economic analysis accompanied a multicenter Department of Veterans Affairs randomized, controlled trial of perioperative total parenteral nutrition (TPN). The cost of providing TPN for an average of 16.15 days before and after surgery was $2405, more than half of which ($1025) included costs of purchasing, preparing, and delivering the TPN solution itself; lipid solutions accounted for another $181, additional nursing care for $843, and miscellaneous costs for $356. Prolonged hospital stay added another $764 per patient to the $2405 cost of providing TPN, bringing the total to $3169. The incremental costs attributed to perioperative TPN were highest ($3921) for the patients least likely to benefit, that is, those who were less malnourished and at low risk of nutrition-related complications. Incremental costs were lowest ($3071) for high-risk patients. On the basis of the hospital-based method of administering TPN that was used in the clinical trial, perioperative TPN did not result in decreased costs for any subgroup of patients.

Wheat bran decreases aberrant crypt foci, preserves normal proliferation, and increases intraluminal butyrate levels in experimental colon cancer.

BACKGROUND: Dietary wheat bran protects against colon cancer, but the mechanism(s) of this effect is not known. Butyrate, produced by colonic bacterial fermentation of dietary polysaccharides, such as wheat bran, induces apoptosis and decreases proliferation in colon cancer cell lines. Whether similar effects occur in vivo is not well defined. We hypothesized that wheat bran's antineoplastic effects in vivo may be mediated in part by butyrate's modulation of apoptosis and proliferation. METHODS: Male F344 rats were fed wheat bran-supplemented or an isocaloric, isonitrogenous fiber-free diet. Rats were treated with one dose of the carcinogen azoxymethane or vehicle with sacrifice after 5 days (tumor initiation); or two doses (days O and 7) with sacrifice after 56 days (tumor promotion). Study variables included fecal butyrate levels and the intermediate biomarkers of colon carcinogenesis, aberrant crypt foci (ACF), and changes in crypt cell proliferation and apoptosis. RESULTS: During tumor initiation, wheat bran produced greater apoptosis (p = .01), a trend toward less proliferation, and preserved the normal zone of proliferation (p = .01). At tumor promotion, wheat bran decreased the number of ACF (proximal colon, p = .005; distal colon, p = .047) and maintained the normal proliferative zone. The fiber-free diet shifted the zone of proliferation into the premalignant pattern in both studies. Wheat bran produced significantly higher fecal butyrate (p = .01; .004, .00001) levels than the fiber-free diet throughout the tumor promotion study. CONCLUSIONS: Wheat bran increased apoptosis and controlled proliferation during tumor initiation and resulted in decreased ACF. Wheat bran's antineoplastic effects occurred early after carcinogen exposure, and were associated with increased fecal butyrate levels.

Economic benefits of aggressive lipid lowering: a managed care perspective.

Coronary heart disease (CHD) has high prevalence in the United States and is associated with significant mortality as well as costs to society. Hyperlipidemia is a major and common modifiable risk factor for CHD. In clinical trials, cholesterol-lowering strategies have a dramatic impact on CHD risk, cardiovascular events, and mortality. Cost-effectiveness data have established that clinical and economic benefits are gained by instituting early and aggressive lipid-lowering therapy. We present new evidence for the clinical benefits and cost effectiveness of aggressive lipid-lowering therapy as primary or secondary prevention of CHD and describe strategies that managed care organizations can take to benefit from a lipid management program.

Clinical trials and external validity.

Although a number of clinical trials are available estimating the benefits of lipid-lowering therapies that include economic end-points, development of modeling methodologies are essential to extend results of those trials over time and to other populations. We reviewed the key issues to be considered when extending trial data to real-world situations. The availability of recent randomized controlled trials of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors in primary and secondary prevention has demonstrated the limitations of earlier modeling efforts to project benefits of lipid modification. The importance of risk stratification is demonstrated, particularly the importance of both LDL and HDL cholesterol either together or as a ratio measure. The selection of modeling methodology to extend benefits of a treatment beyond the end of a trial and over a lifetime is discussed. The relationship between benefits from lipid reduction and risk difference is described, demonstrating that for individuals with established coronary heart disease (CHD) and those older than age 58, benefits from lipid reduction are greater than those predicted from baseline lipid-related risk differences alone. The implications of these data for primary prevention of CHD in the elderly are discussed.

Cutting into cholesterol. Cost-effective alternatives for treating hypercholesterolemia.

We performed an analysis of the cost-effectiveness of treating individuals with significantly elevated levels of total serum cholesterol (greater than 6.85 mmol/L [greater than 265 mg/dL], comparing treatment with three alternative agents: cholestyramine resin, colestipol, and oat bran (a soluble fiber). We simulated a program for lowering cholesterol levels that was similar to that of the Coronary Primary Prevention Trial, and then used the outcomes of the trial to calculate the incremental cost per year of life saved (YOLS) from the perspective of society. Our findings suggest that the cost per YOLS ranges from $117,400 (cholestyramine resin packets) to $70,900 (colestipol packets) and $17,800 (oat bran). Using bulk drug reduces the cost per YOLS to $65,100 (cholestyramine resin) and $63,900 (colestipol). Targeting bulk colestipol treatment only to smokers has a cost per YOLS of $47,010; the incremental cost of treating nonsmokers would be $89,600 per additional YOLS. Although pharmacologic therapy has substantial costs, it may be more cost-effective when low-cost forms are applied to particular high-risk groups, such as smokers. However, a broad public health approach to lowered cholesterol levels by additional dietary modification, such as with soluble fiber, may be preferred to a medically oriented campaign that focuses on drug therapy.

Cholesterol and coronary heart disease: predicting risks by levels and ratios.

OBJECTIVE: Comparison of four measures of cholesterol for predicting men and women who will develop coronary heart disease within 8 to 10 years. DESIGN: Cohort study. PATIENTS: 1898 men who received placebo (the placebo group of the Lipid Research Clinics [LRC] Coronary Primary Prevention Trial [CPPT]), 1025 men and 1442 women who participated in the 1970-1971 Framingham Heart Study biennial examination, and 1911 men and 1767 women without coronary heart disease who were from the LRC Population Prevalence Study. MEASUREMENTS: Total cholesterol, low-density lipoprotein (LDL) cholesterol, ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol, and the ratio of LDL to HDL. Outcomes were coronary heart disease in the CPPT and Framingham studies and death from coronary heart disease in the Prevalence Study. RESULTS: Independent information in the total cholesterol/HDL ratio added risk-discriminating ability to total cholesterol and LDL cholesterol measures (P < 0.02), but the reverse was not true. Among women, a high-risk threshold of 5.6 for the total cholesterol/HDL ratio identified a 0% to 15% larger group at 25% to 45% greater risk in the Prevalence and Framingham studies, respectively, than did current guidelines. Among men in the same studies, a risk threshold of 6.4 for the total cholesterol/HDL ratio identified a 69% to 95% larger group at 2% to 14% greater risk than did LDL cholesterol levels alone. Eight-year likelihood ratios for coronary heart disease ranged from 0.32 to 3.11 in men and from 0.59 to 2.98 in women for total cholesterol/HDL ratios (grouped from < 3 to > or = 9). CONCLUSIONS: The total cholesterol/HDL ratio is a superior measure of risk for coronary heart disease compared with either total cholesterol or LDL cholesterol levels. Current practice guidelines could be more efficient if risk stratification was based on this ratio rather than primarily on the LDL cholesterol level.

Human immunodeficiency virus test evaluation, performance, and use. Proposals to make good tests better.

Human immunodeficiency virus (HIV) tests are essential for detecting asymptomatic infection and are helpful in confirming the diagnoses of acquired immunodeficiency syndrome-related complex and acquired immunodeficiency syndrome. Nonetheless, many aspects of their use remain controversial, partly because of concerns about test accuracy. This article reviews the scientific basis for the evaluation, performance, and use of the most commonly employed HIV assays. Current test performance could be improved by better standardization of test procedures and institution of mandatory proficiency testing and licensure of clinical laboratories that perform HIV testing. Test utility could be enhanced by sequencing tests more appropriately and by interpreting test results in conjunction with the clinical purpose for which the test is being used and the characteristics of the population under study. Finally, HIV tests should be evaluated in a manner that minimizes spectrum and referral bias and inadequate reference standard confirmation, problems that have affected the evaluation of current tests.

KIE: The authors review the literature on the accuracy of currently employed tests for human immunodeficiency virus (HIV) infection and urge improvements in standardization of procedures, mandatory proficiency testing, and licensing of clinical laboratories doing such tests. They discuss test use in several voluntary and mandatory situations; attendant problems of anonymity, confidentiality, and informed consent; and the need to consider ethical principles in defining, quantifying, and balancing the risks and benefits to the parties involved.