Screening for breast cancer: time, travel, and out-of-pocket expenses.

BACKGROUND: We estimated the personal costs to women found to have a breast problem (either breast cancer or benign breast disease) in terms of time spent, miles traveled, and cash payments made for detection, diagnosis, initial treatment, and follow-up. METHODS: We analyzed data from personal interviews with 465 women from four communities in Florida. These women were randomly selected from those with a recent breast biopsy (within 6-8 months) that indicated either breast cancer (208 women) or benign breast disease (257 women). One community was the site of a multifaceted intervention to promote breast screening, and the other three communities were comparison sites for evaluation of that intervention. All P values are two-sided. RESULTS: In comparison with time spent and travel distance for women with benign breast disease (13 hours away from home and 56 miles traveled), time spent and travel distance were statistically significantly higher (P<.001) for treatment and follow-up of women with breast cancer (89 hours and 369 miles). Personal financial costs for treatment of women with breast cancer were also statistically significantly higher (breast cancer = $604; benign breast disease = $76; P < .001) but were statistically significantly lower for detection and diagnosis (breast cancer = $170; benign breast disease = $310; P < .001). Among women with breast cancer, time spent for treatment was statistically significantly lower (P = .013) when their breast cancer was detected by screening (68.9 hours) than when it was detected because of symptoms (84.2 hours). Personal cash payments for detection, diagnosis, and treatment were statistically significantly lower among women whose breast problems were detected by screening than among women whose breast problems were detected because of symptoms (screening detected = $453; symptom detected = $749; P = .045). CONCLUSION: There are substantial personal costs for women who are found to have a breast problem, whether the costs are associated with problems identified through screening or because of symptoms.

Effects of total parenteral nutrition and chemotherapy on the metabolic derangements in small cell lung cancer.

Changes in energy metabolism, substrate use, and hormone profiles were prospectively studied in 31 patients with small cell lung cancer receiving chemotherapy. Patients were randomized to receive either 4 weeks of total parenteral nutrition (n = 15) or to continue self-regulated p.o. diet (control group; n = 16). The initial actual resting energy expenditure measured by indirect calorimetry was 31% higher than the predicted resting energy expenditure determined by the Harris-Benedict formula. The p.o. calorie intake was inappropriately low for these hypermetabolic patients. Total parenteral nutrition resulted in a significant positive net energy balance, but in follow-up was associated with prolonged anorexia and a negative energy balance. Complete response to therapy reduced resting energy expenditure and increased calorie intake, whereas the contrary was true in nonresponders. Elevated plasma-free fatty acids (800 +/- 62 microM; S.E.) and a low respiratory quotient (0.74 +/- 0.02) indicate that the dominant energy source in patients with small cell lung cancer is fat, and that increased fat oxidation continues despite tumor response. Elevated fasting plasma catecholamines and insulin resistance may contribute to continued fat mobilization. Initially, there was a significant increase in blood lactate (1118 +/- 95 microM) suggesting either increased tumor or tumor-mediated glycolytic activity. Response to therapy was associated with a fall in blood lactate levels. The most effective way of improving the metabolic derangements in patients with small cell lung cancer was to achieve tumor response to therapy.

When was a "negative" clinical trial big enough? How many patients you needed depends on what you found.

"Negative" clinical trials that conclude that neither of the treatments is superior are often criticized for having enrolled too few patients. These criticisms usually are based on formal sample size calculations that compute the numbers of patients required prospectively, as if the trial had not yet been carried out. We suggest that this "prospective" sample size calculation is incorrect, for once the trial is over we have "hard" data from which to estimate the actual size of the treatment effect. We can either generate confidence limits around the observed treatment effect or retrospectively compare it with the effect hypothesized before the trial. If the observed effect is small, the risk of the false-negative conclusion (and the sample size required to draw negative or equivalency conclusions) is often much less than that generated by the "prospective" calculation.

Percutaneous injuries among health care workers. The real value of human immunodeficiency virus testing of 'donor' blood.

A decision analysis was conducted to examine whether health care workers should receive short-term (42 days) zidovudine treatment following percutaneous exposure to blood, as well as to determine the value of testing "donor" (patient's) blood. Three alternative options were analyzed: treat all, treat none, and test. In the treat all option, all health care workers receive short-term zidovudine therapy immediately after exposure; in the treat none option, no one receives zidovudine; and in the test option, donor blood is tested, and if it is human immunodeficiency virus (HIV) positive, zidovudine is given. Baseline variables were obtained from the literature. Each outcome was expressed as a utility; this is a method of quantifying the values that persons place on different health states. The results showed that the test option was preferred. Sensitivity analyses indicated that even if the risk of seroconversion were zero or the effectiveness of zidovudine were zero or the drug were withheld, this option was preferred, thus indicating some value of testing other than merely identifying health care workers who should receive zidovudine. In the baseline analysis, this was derived from the fact that approximately 95% of the health care workers would be reassured by a negative test; ie, only approximately 5% of donors are HIV positive. If the prevalence of HIV seropositivity exceeded 42%, the treat none option was preferred. This was found to be due to the fact that increased numbers of health care workers would be told that they were exposed to HIV-positive blood. The "worrying factor" associated with such an exposure was such that above 42% HIV seropositivity, the treat none option was preferred overall. Thus, the real value of testing donor blood is in identifying those persons (greater than 95%) who could be told that they were exposed to HIV-negative blood, that is, reducing their worrying factor to zero. Because acquired immunodeficiency syndrome is a fatal disease, and given that zidovudine is the only available therapeutic option at present, the drug has an important role to play if its effectiveness is greater than zero.

Cardiac assessment for patients undergoing noncardiac surgery. A multifactorial clinical risk index.

In this article, we describe a multifactorial cardiac risk index that can be used to assess patients undergoing noncardiac surgery. The index is a modified version of an index that was previously generated by Goldman and coworkers on a set of 1001 consecutive patients and prospectively validated in our clinical setting (a general medical consultation service in a large teaching hospital) on 455 patients. We present a Bayesian approach to assessing cardiac risks by converting average risks for patients undergoing particular surgical procedures (pretest probabilities) to average risks for patients with each index score (posttest probabilities). A simple nomogram is presented for performing such a calculation.

Economic analysis of low-dose heparin vs the low-molecular-weight heparin enoxaparin for prevention of venous thromboembolism after colorectal surgery.

BACKGROUND: Low-dose heparin and low-molecular-weight heparin are effective strategies for preventing venous thromboembolism in colorectal surgery. The economic attractiveness of these 2 strategies in North America is unknown. We conducted an economic analysis of low-dose heparin calcium compared with enoxaparin sodium, a low-molecular-weight heparin, for thromboembolism prophylaxis after colorectal surgery. METHODS: We used decision analysis, with an economic perspective of a third-party payer. Efficacy data were obtained from the Canadian Multicentre Colorectal Deep Vein Thrombosis Prophylaxis Trial and a literature review. Canadian costs for diagnosis and treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), and major bleeding were obtained from chart review and a national hospital database of colorectal surgery; American costs were obtained from published literature. The main outcomes were incremental benefits (symptomatic DVTs, symptomatic PEs, and major bleeding events avoided) and incremental costs for every 1000 patients treated. RESULTS: In the Canadian Colorectal Trial, the relative risk of DVT and PE for enoxaparin compared with low-dose heparin was 1.0 (95% confidence interval, 0.7-1.5), and the relative risk of major bleeding was 1.8 (95% confidence interval, 0.8-3.9). With the use of these data in the baseline analysis, a strategy of enoxaparin prophylaxis was associated with equal numbers of symptomatic DVTs and PEs, and an excess of 12 major bleeding episodes for every 1000 patients treated, with an additional cost of $86 050 (Canadian data) or $145 667 (US data). In a sensitivity analysis using optimal assumptions for efficacy and safety of enoxaparin (relative risk of DVT, 0.8; relative risk of PE, 0.4; relative risk of major bleeding, 1.0), a strategy of enoxaparin prophylaxis was associated with 0.8 fewer symptomatic DVT, 3 fewer symptomatic PEs, and equal numbers of major bleeding episodes for every 1000 patients treated, with an additional cost of $15 217 (Canadian data) or $107 614 (US data). CONCLUSION: Although heparin and enoxaparin are equally effective, low-dose heparin is a more economically attractive choice for thromboembolism prophylaxis after colorectal surgery.

Charges for medical care at different hospitals.

BACKGROUND: The United States has a high proportion of people without health insurance (15%) and a low proportion of people without employment (5%), resulting in millions who lack insurance but have some ability to pay. We tested whether hospitals charge similar prices for well-specified elective services to individuals paying out-of-pocket for medical care. METHODS: We surveyed the 2 largest general hospitals from every large city (population >500 000) in the United States and Canada. At each hospital we evaluated 5 diagnostic, 7 therapeutic, and 3 nonclinical services to determine the total charge to patients who pay directly. RESULTS: Overall, 66 hospitals were included (average, 758 beds; not-for-profit, 97% [n = 64]; teaching, 80% [n = 53]). The range in charges was substantial; for example, a screening mammogram was $40 at one hospital in Los Angeles, Calif, and $346 at one hospital in Quebec City. Charges for a screening mammogram were relatively stable between 1996 and 1997 (r=0.79; 95% confidence interval, 0.68-0.87) and unrelated to the hospital's location or charges for other services. The relative amount of variation in charges was similar for high-priced and low-priced services, similar for diagnostic and therapeutic services, and similar for the United States and Canada. CONCLUSIONS: Charges for the same hospital service vary substantially. Greater visibility might reduce some variation by bringing outliers into closer scrutiny. Patients seeking care and paying out-of-pocket could save financially by comparison shopping.

Efficacy of pneumococcal vaccination in adults. A meta-analysis of randomized controlled trials.

BACKGROUND: Because of the prevalence of pneumococcal pneumonia, the substantial morbidity and mortality associated with many pneumococcal infections, and an increase in the incidence of antibiotic resistance among pneumococcal isolates, considerable efforts for disease prevention have been made using a polyvalent polysaccharide pneumococcal vaccine. Despite numerous clinical trials of the vaccine, its efficacy in the prevention of pneumococcal infections and other clinically relevant medical outcomes in adults remains uncertain. METHODS: To assess quantitatively the efficacy of pneumococcal vaccination, a MEDLINE literature search, manual reviews of article bibliographies, and communications with pneumococcal vaccine investigators were used to identify randomized controlled trials of the pneumococcal vaccine. Independent review of 594 articles revealed nine randomized trials with 12 vaccine and control study groups that evaluated clinically relevant outcomes in adults. To estimate a summary effect size for all outcomes, Mantel-Haenszel odds ratios (ORs) and Dersimonian and Laird rate differences (RDs) and their associated 95% confidence intervals (CIs) were computed. RESULTS: Summary ORs demonstrated a statistically significant protective effect of the vaccine for four pneumococcal infection-related outcomes: definitive pneumococcal pneumonia (OR = 0.34; 95% CI = 0.24 to 0.48), definitive pneumococcal pneumonia for vaccine-containing pneumococcal antigen types only (vaccine types only) (OR = 0.17; 95% CI = 0.09 to 0.33), presumptive pneumococcal pneumonia (OR = 0.47; 95% CI = 0.35 to 0.63), and presumptive pneumococcal pneumonia (vaccine types only) (OR = 0.39; 95% CI = 0.26 to 0.59). The summary RDs, which account for heterogeneity among studies, confirmed a statistically significant protective effect for two of these same outcomes: definitive pneumococcal pneumonia (RD = 4/1000; 95% CI = 0/1000 to 7/1000) and definitive pneumococcal pneumonia (vaccine types only) (RD = 8/1000; 95% CI = 1/1000 to 16/1000). Summary ORs and RDs failed to demonstrate a protective effect for pneumonia (all causes), bronchitis, and mortality (all causes) or mortality due to pneumonia or pneumococcal infection. Subgroup analyses showed that for all four pneumococcal infection-related outcomes, vaccine efficacy differed for high- and low-risk subjects, demonstrating efficacy for low-risk subjects and lack of efficacy for high-risk subjects. CONCLUSIONS: Pneumococcal vaccination appears efficacious in reducing bacteremic pneumococcal pneumonia in low-risk adults. However, evidence from randomized controlled trials fails to demonstrate vaccine efficacy for pneumococcal infection-related or other medical outcomes in the heterogeneous group of subjects currently labeled as high risk.

Preferences for home vs hospital care among low-risk patients with community-acquired pneumonia.

OBJECTIVE: To measure preferences for initial outpatient vs hospital care among low-risk patients who were being actively treated for community-acquired pneumonia (CAP). METHODS: Study patients included 159 patients with CAP, 57 (36%) initially hospitalized, who were identified as being at low risk for early mortality using a validated prediction model. Subjects were enrolled from university and community health care facilities located in Boston, Mass, Halifax, Nova Scotia, and Pittsburgh, Pa, participating in the Pneumonia Patient Outcome Research Team prospective cohort study of CAP. Three utility assessment techniques (category scaling, standard gamble, and willingness to pay) were used to measure the strength of patient preferences for the site of care for low-risk CAP. At the time of initial therapy or during the early recuperative period, patient preferences were assessed across a spectrum of potential clinical outcomes using 7 standardized pneumonia clinical vignettes. RESULTS: Responses to the 7 pneumonia scenarios indicated that most patients consistently preferred outpatient-based therapy. This pattern was observed regardless of whether patients had actually been treated initially at home or in a hospital. Patients (74%) who stated that they generally preferred home care for low-risk CAP were willing to pay a mean of 24% of 1 month's household income to be assured of this preference. Preference for home care, as measured by the category scaling and the willingness to pay, persisted after adjustment for sociodemographic and baseline health status covariates. Sixty nine percent of interviewed patients said that their physician alone determined whether they would be treated in the hospital or at home. Only 11% recalled being asked if they had a preference for either site of care. CONCLUSIONS: Most patients, even those treated initially in a hospital, who were at low risk for mortality from CAP prefer outpatient treatment. However, most physicians appear not to involve patients in the site-of-care decision. More explicit discussion of patient preferences for the location of care would likely yield more highly valued care by patients as well as less costly treatment for CAP.

Skeletal muscle function in chronic renal failure: an index of nutritional status.

To determine whether skeletal muscle function testing (SMF) provides an index of nutritional status in patients with chronic renal failure (CRF), two groups with comparable CRF were studied. In 48 well-nourished (WN) and 17 malnourished (MN) patients with stable CRF, and in 33 WN nonazotemic controls, adductor pollicis function was assessed. The force at 10 Hz was expressed as a % of force at 100 Hz (F10/F100), and maximal relaxation rate (MRR) as % force loss/10 ms. Standard nutritional assessment was also performed. The WN group was not significantly different from controls for either F10/F100 or MRR. The F10/F100 of the MN group was significantly greater than either the WN group or controls (p less than 0.001), while MRR was less (p less than 0.001). Significant malnutrition by conventional parameters was shown in patients with abnormal F10/F100, and also in patients with abnormal MRR. Hence, SMF as described is unaffected by azotemia, and provides a functional measure of nutritional status in CRF.

Effect of diagnostic testing for multiple sclerosis on patient health perceptions. Rochester-Toronto MRI Study Group.

BACKGROUND AND METHODS: We examined the effect on health perceptions of a diagnostic workup in 172 patients with suspected multiple sclerosis (MS) using two questionnaires (Mishel, Rand Medical Outcome Study) and three visual analogue scales measuring distress. Patients were categorized into "MS," "not MS," or "still uncertain" groups. RESULTS: Patients with a definitive diagnosis reported a significant decrease in uncertainty (analysis of variance [ANOVA] P = .0004). The Medical Outcome Study showed a slightly worsened perceived current health status (ANOVA P = .02) and future health outlook (ANOVA P = .001) in the MS group compared with the other two groups. Distress over physical symptoms decreased in all three groups and anxiety was more likely to decrease than increase even in those with MS. Prognostic uncertainty distress decreased in the not MS group and still uncertain groups, whereas it remained unchanged in the MS group (P = .9156). CONCLUSION: Significant and generally beneficial changes in patient health perceptions are seen associated with a neurologic workup in suspected MS, irrespective of the final diagnosis.

A randomized trial of test result sequencing in patients with suspected multiple sclerosis. Rochester-Toronto MRI Study Group.

BACKGROUND AND METHODS: We performed a randomized trial of the incremental impact of high-volume contrast computed tomographic scan of the brain plus trimodal evoked potentials vs magnetic resonance imaging of the brain on neurologists' diagnostic labeling of patients with suspected multiple sclerosis (MS). Two hundred and four patients with suspected MS (clinically possible 59% or probable 41%-McAlpine criteria) were assessed by two neurologists. Patients were diagnostically categorized after reviewing the results of the tests presented in random order. RESULTS: Most of the change in diagnostic categorization occurred after presenting the first test result irrespective of result sequence (chi 2 = 0.01, P = .99). The diagnoses became more definitive when all test results were available (P < .001). Magnetic resonance imaging and evoked potential were suggestive of MS equally frequently (chi 2 = 0.57, P = .45). CONCLUSION: In suspected MS, there is no difference in diagnostic effect between brain magnetic resonance image scanning and computed tomography plus trimodal evoked potentials.

The effect of spectrum bias on the utility of magnetic resonance imaging and evoked potentials in the diagnosis of suspected multiple sclerosis.

BACKGROUND: Spectrum bias is the tendency for the effectiveness of a test (or treatment) to vary as a function of clinical, pathologic, or comorbid variables including disease severity. Our null hypothesis was that within the population of suspected multiple sclerosis (MS) patients, there would be no difference in MRI and evoked potential (EP) sensitivity and specificity between those with mild MS versus those with more severe clinical signs of the disease, i.e., that spectrum bias is not a factor. METHODS: Three hundred three patients with suspected MS were evaluated by a board-certified neurologist, then scanned with MRI. Two hundred four patients also received EP testing. RESULTS: The sensitivity of MRI in patients with suspected MS was 58 percent with a false-positive rate of 9%. The overall sensitivity was 64% in the probable and 45% in the possible group. In the low pretest probability group sensitivity was 20%, and it was 70% in the high pretest probability group. These differences in sensitivity are statistically significant (p < 0.03). In contrast, the specificity between groups did not differ significantly. EP sensitivity was 69% in the high probability subgroup and 5% in the low probability subgroup. (p < 0.01). CONCLUSION: In this study, both EP and MRI results demonstrated an association between disease frequency, disease severity, and test sensitivity with greater disease frequency and intensity suggesting more impressive diagnostic test performance. The distorting effect of the variable clinical severity on MRI and EP sensitivity in suspected MS underscores that diagnostic tests perform differently in different groups of patients.

Gallium-67 scanning in the diagnosis of postoperative sternal osteomyelitis: concise communication.

Sternal osteomyelitis is an uncommon but serious complication of the median sternotomy incision. Definite diagnosis is clinically difficult and radionuclide scanning is of uncertain value in the early postoperative period. We conducted a prospective blind study of gallium scanning in the early period after cardiac surgery and reviewed clinically diagnosed cases that also had scans. Clinical status and scan interpretation were each independently assessed by three raters. Thirty-eight scans included six true positives, five true negatives (no sternotomy) and 27 post-sternotomy, clinically uninfected patients. Using categories of high, medium, and low for scan interpretation, the radiologic assessors agreed 90% of the time. Normal postoperative Ga-67 uptake could usually be differentiated from uptake by an infected sternum. The test had a sensitivity of 83% and specificity 96%. If the clinical (pretest) likelihood of sternal osteomyelitis is 30%, then the gallium scan will have a 90% positive predictive value and a 93% negative predictive value. This study of observer variation and validity indicates that Ga-67 scanning may be useful in confirming the diagnosis of poststernotomy sternal osteomyelitis.

Meta-analysis in medical research: strong encouragement for higher quality in individual research efforts.

In this article, we counter some criticism regarding the desirability of performing meta-analysis in clinical research. These criticisms, we argue, are based mainly on current difficulties in deriving firm conclusions based on meta-analysis, resulting from poor methodology and reporting of primary studies. This is not a fault of meta-analysis. In fact, with a better understanding of meta-analysis in the context of the full scientific research process, meta-analysis is seen as a key element for improving individual research efforts and their reporting in the literature. This in turn will further enhance the role of meta-analysis in helping clinicians and policy makers answer clinical questions.

Incorporating variations in the quality of individual randomized trials into meta-analysis.

Meta-analysis is a method of synthesizing evidence from multiple sources. It has been increasingly applied to combine results from randomized trials of therapeutic strategies. Unfortunately there is often variation in the quality of the trials that are included in meta-analyses, limiting the value of combining the results in an overview. This variation in quality can lead to both bias and reduction in precision of the estimate of the therapy's effectiveness. There are a number of methods for quantifying the quality of trials including the detailed Chalmers system and simple scales. The nature of the relationship between these quality scores and the true estimate of effectiveness is unknown at this time. We discuss four methods of incorporating quality into meta-analysis: threshold score as inclusion/exclusion criterion, use of quality score as a weight in statistical pooling, visual plot of effect size against quality score and sequential combination of trial results based on quality score. The last method permits an examination of the relation between quality and both bias and precision on the pooled estimates. We conclude that while it is possible to incorporate the effect of variation of quality of individual trials into overviews, this issue requires more study.

A randomized trial of a decisional aid for mental capacity assessments.

The objective of this study was to evaluate the clinical utility of a decisional aid for mental capacity assessments which was developed using a group judgment methodology. This was carried out by a randomized, controlled trial. The subjects comprised 64 University of Toronto psychiatry residents in postgraduate years 1 through 4. Residents were randomized to carry out mental capacity assessments on simulated cases with, or without, the use of the decisional aid. The main outcome measure was the extent of agreement between the mental capacity determinations of residents and those of experts. There was no difference between the intervention and control groups with respect to the overall mean level of agreement with experts (0.87 vs 0.86, p = 0.88; 95% confidence interval for the difference between the study groups, -0.07 to +0.08). A logistic regression analysis, which adjusted for imbalances between the groups, also revealed no difference between the groups in their agreement with experts. The mean time per competency assessment was significantly longer in the intervention group (19.1 vs 10.8 min; p < 0.001). It was concluded that the decisional aid did not improve the ability of the psychiatry residents to make mental capacity assessments on simulated cases. Despite relatively limited formal training, the psychiatry residents had a high level of agreement with experts.

Surgical decision analysis: esophagectomy/esophagogastrectomy with or without drainage?

Decision analysis was used to compare three management strategies for patients undergoing esophagogastrectomy for carcinoma of the esophagus or gastric cardia: drain all patients with either pyloromyotomy or pyloroplasty, drain no patient, or perform a test that stratifies patients into high-risk and low-risk groups for development of gastric outlet obstruction and drain the high-risk group. Results indicate that a "drain all" approach is appropriate in clinical settings where the risk of gastric outlet obstruction is greater than 10%, as long as the drainage procedure is 95% effective. If a test were developed to stratify patients, it would have to have a sensitivity of 80% when its specificity was 100%, and would require a higher sensitivity as the specificity fell below 100%.

Surgery versus stereotactic radiosurgery for small, operable cerebral arteriovenous malformations: a clinical and cost comparison.

OBJECTIVE: Cerebral arteriovenous malformations (AVMs) may cause stroke and death in young patients. For small AVMs, the major curative treatment options are surgery and stereotactic radiosurgery (SR). Although the initial costs and risks of SR are less, there is a latency to cure and ultimately the success rate is lower than with surgery. Thus, these two treatment modalities were compared with respect to clinical outcomes and associated costs by means of a cost-effectiveness analysis. METHODS: A decision analysis model was developed using Smltree software (J.P. Hollenberg, Roslyn, NY). Probability estimates for cure and complications for both therapies were derived from the literature. Utility values for minor and major stroke were measured in patients with AVMs who were treated at the University of Toronto clinic, using the standard gamble technique. Costs were obtained from several sources, including the case costing systems of several hospitals in Ontario, Canada. RESULTS: Surgery confers a 0.98 quality-adjusted life year (QALY) advantage over SR, at an additional cost of $6937 per patient. Thus, from a societal perspective, the incremental cost-effectiveness ratio is $7100 per QALY for a patient treated surgically. The result is sensitive to only two variables: surgical morbidity and surgical mortality. However, the preferred treatment strategy changes to favor SR only at the extreme high end of the possible range for these variables, when the rate of permanent neurological morbidity resulting from surgery exceeds 12% or the surgical mortality rate exceeds 4%. CONCLUSIONS: In the treatment of small AVMs, surgery confers a large clinical benefit over SR. The reason is that surgery protects the patient from hemorrhage earlier and with greater success than does SR. The associated cost-effectiveness ratio, $7100/QALY, is highly economically attractive. Therefore, surgery achieves important improvements in clinical outcomes and is associated with an excellent ratio of incremental costs per QALY gained.

A controlled trial of the effect of parenteral nutritional support on patients with respiratory failure and sepsis.

Energy and protein metabolism was studied in 11 septic patients receiving ventilatory support while on three different intravenous regimens. They received 5% dextrose in water (D5W), and one of two different regimens of parenteral nutritional support (PNS); either amino acid and dextrose (PNA) or amino acid and dextrose and lipid (PNB). All patients were given D5W and PNS in random order. The energy intake was targetted to exceed by 50% the measured metabolic rate. On D5W the mean measured energy expenditure was only 15.2% above the expected energy expenditure (p<0.02). A respiratory quotient of 0.75 while on D5W showed that in the absence of PNS the major part of energy requirements came from fat oxidation. In addition, on D5W these patients were in negative nitrogen and protein (synthesis-catabolism) balance. With PNS the metabolic rate rose significantly (p<0.02). While on PNA, the CO2 production was significantly higher than with PNB, and despite receiving all non-protein energy as glucose, the patients continued to oxidise fat to meet about 30% of their energy requirements. Continued fat oxidation was found to be associated with insulin resistance and high catecholamine levels, suggesting a cause and effect relationship. PNS caused an increase in protein (synthesis - catabolism) and nitrogen balances, and reduced leucine oxidation. The fall in leucine oxidation was greater on PNB than on PNA. Protein and nitrogen balances, expressed per gram of amino acid infused, were significantly better with PNB than PNA. It was concluded that insulin resistance may make fat an efficient source of energy.