Economic evaluation of linezolid, flucloxacillin and vancomycin in the empirical treatment of cellulitis in UK hospitals: a decision analytical model.

Standard antibiotic treatment of infections has become more difficult and costly due to treatment failure associated with the rise in bacterial resistance. New antibiotics that can overcome such resistant pathogens have the potential for great clinical and economic impact. Linezolid is a new antibiotic that is effective in the treatment of both antibiotic-susceptible and antibiotic-resistant Gram-positive bacterial infections, including those resistant to other available antibiotics. This breadth of activity is unique in existing antibiotics for Gram-positive bacteria and serves as the rationale for exploring the hypothesis that linezolid is an appropriate choice when considering empirical treatment of cellulitis in complicated or compromised patients in the nosocomial setting. A decision-modelling approach was used to compare the predicted first-line treatment efficacy and direct medical costs of linezolid with standard treatment of cellulitis among hospitalized patients. For the purposes of this analysis, standard care is defined along two main pathways: (1) initiating care with intravenous (iv) flucloxacillin, switching to vancomycin if the pathogen is found to be resistant to flucloxacillin, or maintaining flucloxacillin if the pathogen is found susceptible, or when culture and sensitivity analysis is inconclusive; or (2) initiating care with vancomycin, switching to iv flucloxacillin if the pathogen is found susceptible to flucloxacillin, maintaining vancomycin if the infection is found resistant, or when culture and sensitivity are inconclusive. For those patients taking iv flucloxacillin, a switch to oral flucloxacillin was allowed when clinically appropriate. We hypothesized that the cost of care of initiating treatment with linezolid would be less than that for both vancomycin and flucloxacillin in resistance risk ranges typically encountered in UK hospitals. In addition, while the registration trials showed equivalence of linezolid with the comparators in known or suspected methicillin-resistant Staphylococcus aureus (MRSA) and in known or suspected methicillin-susceptible Staphylococcus aureus (MSSA) (vancomycin and oxacillin) respectively, we hypothesized that first-line success rates would be higher in empiric treatment with linezolid. Efficacy data were obtained from recent clinical trials with linezolid and standard treatment, and medical resource utilization was obtained from an expert panel of clinicians who were questioned regarding resistant and susceptible infections separately. UK hospital direct medical costs of treatment were determined using standard costing techniques. Base case analyses assumed a residual 80% unknown pathogen rate after culture and susceptibility based on a physician survey and supported in the literature. The analysis in this model predicts that initiating empirical treatment of cellulitis with linezolid will (1) result in higher overall success rates than flucloxacillin for first-line treatment, regardless of resistance risk and (2) be less costly than initiating treatment with flucloxacillin when the likelihood of a patient being infected by a resistant pathogen is greater than 24.1%. Furthermore, initiating treatment with linezolid is predicted to result in higher overall success rates and be less costly than vancomycin across the entire spectrum of the patients' risk of being infected by a resistant pathogen.

The energy expenditure of postmenopausal women classified as restrained or unrestrained eaters.

OBJECTIVE: Restrained eating is a common dietary practice among individuals who are attempting to prevent weight gain, but little is known about differences in energy physiology and regulation between restrained and unrestrained eaters. We investigated this issue in non-obese free-living postmenopausal women classified as long-term restrained (n=26) or unrestrained (n=34) eaters group matched for body mass index (BMI). MEASUREMENTS: Measurements were made of total energy expenditure (TEE), resting energy expenditure (REE), body composition, reported leisure time activity, maximal aerobic capacity (VO2max) and weight change during the study period. In addition, physical activity level (PAL) and nonexercise activity thermogenesis (NEAT) were calculated from measured variables. RESULTS: There were no significant differences between the groups in body composition, weight change, aerobic capacity or total leisure time activity. Relationships between fat-free mass (FFM) and both REE and TEE, and the relationship between work load and energy expenditure in the test of maximal oxygen consumption, were also not different between groups. However, restrained eaters had a significantly lower PAL (equal to TEE/REE, 1.72+/-0.04 vs 1.84+/-0.04, P<0.05). In addition, in multiple regression models predicting NEAT, NEAT was significantly lower in restrained eaters than unrestrained eaters and there was a positive relationship between NEAT and weight change in unrestrained eaters but no relationship in restrained eaters (P<0.05). CONCLUSIONS: In contrast to a previous report, we found no significant difference in TEE between restrained and unrestrained eaters. PAL was slightly lower in restrained eaters, apparently due to reduced NEAT, and restrained eaters also lacked the positive association between NEAT and body weight change seen in unrestrained eaters. This latter finding, if confirmed in future studies, could help explain an increased susceptibility of restrained eaters to weight gain. SPONSORSHIP: NIH grants AG12829, DK46124 and T32AG00209, and US Cooperative Agreement number 58-1950-9-001.

Psychological measures of eating behavior and the accuracy of 3 common dietary assessment methods in healthy postmenopausal women.

BACKGROUND: Factors affecting the accuracy of reported energy intake (rEI) need to be identified. OBJECTIVE: Our objective was to investigate the association of psychological measures of eating behavior with the accuracy of rEI assessed by 7-d weighed intakes, a 24-h recall, and a food-frequency questionnaire. DESIGN: Subjects were 26 restrained eaters aged 60.3 +/- 0.6 y (mean +/- SEM) and weighing 63.8 +/- 1.7 kg and 34 unrestrained eaters aged 59.4 +/- 0.6 y and weighing 64.0 kg. rEI was assessed by using 3 dietary assessment methods and total energy expenditure (TEE) was determined by using doubly labeled water. Calculated EI (cEI) was determined as TEE corrected for the estimated change in body energy. Subjects completed the Eating Inventory. RESULTS: rEI values were significantly lower than TEE values for all 3 dietary assessment methods (P < 0.05); there was no significant relation between rEI and TEE by any method. There was no significant difference in 100 x rEI:TEE between restrained and unrestrained eaters by any of the dietary assessment methods. When combined data from the 3 methods were used, 100 x rEI:cEI was not significantly different from 100% in unrestrained eaters (99 +/- 6.8%) but was lower in restrained eaters (89.1 +/- 5.3%; P < 0.05). There was a positive relation between hunger and 100 x rEI:TEE (P < 0.05). CONCLUSIONS: Low hunger is associated with undereating relative to normal eating during measurement of dietary intake; high dietary restraint may be associated with a reduction in reporting of consumed foods. Dietary hunger and restraint assessed with use of the Eating Inventory may help to identify subjects likely to underreport dietary intake.

Overeating in America: association between restaurant food consumption and body fatness in healthy adult men and women ages 19 to 80.

PURPOSE: To examine the association between the frequency of consuming restaurant food and body fatness in adults. RESEARCH METHODS AND PROCEDURES: Usual free-living dietary intake and the frequency of consuming food from seven different restaurant types (fried chicken, burger, pizza, Chinese, Mexican, fried fish, and "other") were assessed by food frequency questionnaire in 73 healthy men and women [ages 19 to 80, body mass index (BMI) 18 to 33]. In addition, body fatness (percent weight) was determined by hydrostatic weighing, and physical activity and other lifestyle parameters were assessed by questionnaire. The relationship between the frequency of consuming restaurant food and body fatness was determined after controlling for age, sex, and other confounders by using multiple regression techniques. RESULTS: Restaurant food consumption averaged 7.5+/-8.5 (Standard Deviation) times/month. After controlling for age and sex, the frequency of consuming restaurant food was positively associated with body fatness (partial r = 0.36, p = 0.003). The strength of this association did not change after controlling for education level, smoking status, and alcohol intake, but after additionally controlling for physical activity, the partial r increased to 0.42 (p = 0.004). Total daily intakes of energy, fat, and fiber were significantly associated with restaurant food consumption frequency (r = 0.59, 0.28, and -0.45, respectively, p = 0.02 to 0.0001). DISCUSSION: The frequency of consuming restaurant food was positively associated with increased body fatness in adults. The increasing proportion of household food income spent on food prepared away from home in the United States may therefore help explain the rising national prevalence of obesity.

Equations for predicting the energy requirements of healthy adults aged 18-81 y.

BACKGROUND: Recent studies have questioned the accuracy of using the current recommended dietary allowances (RDAs) to predict usual energy requirements in adults. OBJECTIVE: We developed equations to predict adult energy requirements from simple anthropometric and laboratory measures by using the doubly labeled water method to determine each subject's total energy expenditure (TEE), which is equal to usual energy requirements in weight-stable individuals. DESIGN: This was a cross-sectional study conducted with 93 healthy, free-living adults [44 men and 49 women; body mass index range (in kg/m2): 18.4-31.8] aged 18-81 y. Body fat and fat-free mass were measured by underwater weighing, physical activity was estimated by using activity monitors, and resting energy expenditure was determined by indirect calorimetry. Information on anthropometric variables and reported strenuous activity was also collected. RESULTS: Three regression equations were developed and verified for accuracy by using bootstrap analysis and doubly labeled water data published by other research groups. The first equation used information on only age, weight, height, and sex and had an SEE for prediction of TEE of 1.80 MJ/d. The second and third equations used different combinations of basic and laboratory data and had SEEs of 1.55 and 1.65 MJ/d, respectively. With use of the same analytic approaches, the RDAs for energy were shown to significantly underestimate usual energy needs by approximately 10%; the extent of underestimation was significantly greater for subjects with high TEEs than for subjects with low TEEs. CONCLUSION: Regression equations based on doubly labeled water measurements of TEE appear to be more accurate than the current RDAs for predicting energy requirements in healthy, nonobese adults living in affluent countries.

Dietary variety within food groups: association with energy intake and body fatness in men and women.

BACKGROUND: Short-term experimental studies suggest that dietary variety may influence body fatness but no long-term human studies have been reported. OBJECTIVE: The purpose of this study was to determine whether dietary variety within food groups influences energy intake and body fatness. DESIGN: Seventy-one healthy men and women (aged 20-80 y), who provided accurate reports of dietary intake and completed a body-composition assessment, were studied. RESULTS: Dietary variety was positively associated with energy intake within each of 10 food groups (r = 0.27-0.56, P < 0.05). In multiple regression analysis with age and sex controlled for, dietary variety of sweets, snacks, condiments, entrées, and carbohydrates (as a group) was positively associated with body fatness (partial r = 0.38, P = 0.001) whereas variety from vegetables was negatively associated (partial r = -0.31, P = 0.01) (R2 = 0.46, P < 0.0001). In separate models, both a variety ratio (variety of vegetables/variety of sweets, snacks, condiments, entrées, and carbohydrates) and percentage dietary fat were significant predictors of body fatness (controlled for age and sex, partial r = -0.39 and 0.31, respectively, P < 0.01). However, dietary fat was no longer significantly associated with body fatness when the variety ratio and dietary fat were included in the same model. CONCLUSIONS: Our data, coupled with those of previous short-term studies, suggest that a high variety of sweets, snacks, condiments, entrées, and carbohydrates coupled with a low variety of vegetables promotes long-term increases in energy intake and body fatness. These findings may help explain the rising prevalence of obesity.

The effects of age on postprandial thermogenesis at four graded energetic challenges: findings in young and older women.

There remains controversy over the effect of age on postprandial thermogenesis, with some studies observing decreased postprandial thermogenesis in older subjects and other studies finding no effect of age. We investigated this issue in 8 young (25.2+/-1.8 years) and 8 older (72.2+/-2.1 years) healthy glucose-tolerant women with normal thyroid hormone status. Repeated measures of the thermic effect of feeding (TEF) were obtained following consumption of test meals containing 0, 1046, 2092, and 4184 kilojoules (kJ) by using indirect calorimetry. TEF at each meal size was determined once in the older subjects and twice in the younger subjects (during follicular and luteal phases of the menstrual cycle) for a total of 96 measurements. There was a positive dose-response between meal size and TEF (p < .001) that was not significantly affected by age group. The best single predictor of TEF expressed as a percentage of meal energy content was waist-to-hip ratio (R2=67.416, p < .02). These results indicate that aging is not associated with decreased TEF in the absence of factors such as a hypothyroid state or glucose intolerance.