Effect of a national primary care pay for performance scheme on emergency hospital admissions for ambulatory care sensitive conditions: controlled longitudinal study.

OBJECTIVE: To estimate the impact of a national primary care pay for performance scheme, the Quality and Outcomes Framework in England, on emergency hospital admissions for ambulatory care sensitive conditions (ACSCs). DESIGN: Controlled longitudinal study. SETTING: English National Health Service between 1998/99 and 2010/11. PARTICIPANTS: Populations registered with each of 6975 family practices in England. MAIN OUTCOME MEASURES: Year specific differences between trend adjusted emergency hospital admission rates for incentivised ACSCs before and after the introduction of the Quality and Outcomes Framework scheme and two comparators: non-incentivised ACSCs and non-ACSCs. RESULTS: Incentivised ACSC admissions showed a relative reduction of 2.7% (95% confidence interval 1.6% to 3.8%) in the first year of the Quality and Outcomes Framework compared with ACSCs that were not incentivised. This increased to a relative reduction of 8.0% (6.9% to 9.1%) in 2010/11. Compared with conditions that are not regarded as being influenced by the quality of ambulatory care (non-ACSCs), incentivised ACSCs also showed a relative reduction in rates of emergency admissions of 2.8% (2.0% to 3.6%) in the first year increasing to 10.9% (10.1% to 11.7%) by 2010/11. CONCLUSIONS: The introduction of a major national pay for performance scheme for primary care in England was associated with a decrease in emergency admissions for incentivised conditions compared with conditions that were not incentivised. Contemporaneous health service changes seem unlikely to have caused the sharp change in the trajectory of incentivised ACSC admissions immediately after the introduction of the Quality and Outcomes Framework. The decrease seems larger than would be expected from the changes in the process measures that were incentivised, suggesting that the pay for performance scheme may have had impacts on quality of care beyond the directly incentivised activities.

Factors associated with improvement in disability-adjusted life years in patients with HIV/AIDS

Background The epidemic of HIV/AIDS and treatments that have emerged to alleviate, have brought about a shift in the burden of disease from death to quality of life/disability. The aim was to determine which factors are associated with improvements in the level of health of male and female patients with HIV/AIDS in Andalusia, in terms of disability-adjusted life years. Methods Descriptive study based on a sample group of 8800 people on the Andalusian AIDS register between 1983 and 2004. Dependent variables: Life lost due to premature mortality (YLL), years lost due to disability (YLD) and disability-adjusted life years (DALY). Independent variables: vital state, sex, age at the time of diagnosis, age at the time of death, transmission category, province of residence, AIDS-indicator disease and the period of diagnosis. A bivariate analysis was carried out to find out if the health level variables changed in accordance with the independent variables. Using the independent variables which had a statistically significant link with the level of health variables, a multivariate linear regression model, disaggregated by gender, was constructed. Results Amongst the women, we found a model which explained the level of health of 64.9%: a link was found between a higher level of health (lower DALYs) and not intravenous drug use, the province of residence, being diagnosed during the HAART era and older age at the time of diagnosis. Amongst the men, we found a model which explained the level of health of 64.4%: a link was found between a higher level of health (lower DALYs) and intravenous drug use, the province of residence, being diagnosed during the HAART era and older age at the time of diagnosis. Conclusion A higher level of health (lower DALY) amongst both men and women was found to be linked to not be intravenous drug user, the province of residence, being diagnosed during the HAART era and older age at the time of diagnosis.

Decreased PM10 exposure attenuates age-related lung function decline: genetic variants in p53, p21, and CCND1 modify this effect.

BACKGROUND: Decreasing exposure to airborne particulates was previously associated with reduced age-related decline in lung function. However, whether the benefit from improved air quality depends on genetic background is not known. Recent evidence points to the involvement of the genes p53 and p21 and of the cell cycle control gene cyclin D1 (CCND1) in the response of bronchial cells to air pollution. OBJECTIVE: We determined in 4,326 participants of the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) whether four single-nucleotide polymorphisms in three genes [CCND1 (rs9344 [P242P], rs667515), p53 (rs1042522 [R72P]), and p21 (rs1801270 [S31R])] modified the previously observed attenuation of the decline in the forced expiratory flow between 25% and 75% of the forced vital capacity (FEF(25-75)) associated with improved air quality. METHODS: Subjects of the prospective population-based SAPALDIA cohort were assessed in 1991 and 2002 by spirometry, questionnaires, and biological sample collection for genotyping. We assigned spatially resolved concentrations of particulate matter with aerodynamic diameter < or = 10 microm (PM(10)) to each participant's residential history 12 months before the baseline and follow-up assessments. RESULTS: The effect of diminishing PM(10) exposure on FEF(25-75) decline appeared to be modified by p53 R72P, CCND1 P242P, and CCND1 rs667515. For example, a 10-microg/m(3) decline in average PM(10) exposure over an 11-year period attenuated the average annual decline in FEF(25-75) by 21.33 mL/year (95% confidence interval, 10.57-32.08) among participants homozygous for the CCND1 (P242P) GG genotype, by 13.72 mL/year (5.38-22.06) among GA genotypes, and by 6.00 mL/year (-4.54 to 16.54) among AA genotypes. CONCLUSIONS: Our results suggest that cell cycle control genes may modify the degree to which improved air quality may benefit respiratory function in adults.

The effect of post-discharge educational intervention on patients in achieving objectives in modifiable risk factors six months after discharge following an episode of acute coronary syndrome, (CAM-2 Project): a randomized controlled trial

We investigated whether an intervention mainly consisting of a signed agreement between patient and physician on the objectives to be reached, improves reaching these secondary prevention objectives in modifiable cardiovascular risk factors six-months after discharge following an acute coronary syndrome. BACKGROUND: There is room to improve mid-term adherence to clinical guidelines' recommendations in coronary heart disease secondary prevention, specially non-pharmacological ones, often neglected. METHODS: In CAM-2, patients discharged after an acute coronary syndrome were randomly assigned to the intervention or the usual care group. The primary outcome was reaching therapeutic objectives in various secondary prevention variables: smoking, obesity, blood lipids, blood pressure control, exercise and taking of medication. RESULTS: 1757 patients were recruited in 64 hospitals and 1510 (762 in the intervention and 748 in the control group) attended the six-months follow-up visit. After adjustment for potentially important variables, there were, between the intervention and control group, differences in the mean reduction of body mass index (0.5 vs. 0.2; p < 0.001) and waist circumference (1.6 cm vs. 0.6 cm; p = 0.05), proportion of patients who exercise regularly and those with total cholesterol below 175 mg/dl (64.7% vs. 56.5%; p = 0.001). The reported intake of medications was high in both groups for all the drugs considered with no differences except for statins (98.1% vs. 95.9%; p = 0.029). CONCLUSIONS: At least in the short term, lifestyle changes among coronary heart disease patients are achievable by intensifying the responsibility of the patient himself by means of a simple and feasible intervention.

The BRAIN TRIAL: a randomised, placebo controlled trial of a Bradykinin B2 receptor antagonist (Anatibant) in patients with traumatic brain injury

BACKGROUND Cerebral oedema is associated with significant neurological damage in patients with traumatic brain injury. Bradykinin is an inflammatory mediator that may contribute to cerebral oedema by increasing the permeability of the blood-brain barrier. We evaluated the safety and effectiveness of the non-peptide bradykinin B2 receptor antagonist Anatibant in the treatment of patients with traumatic brain injury. During the course of the trial, funding was withdrawn by the sponsor. METHODS Adults with traumatic brain injury and a Glasgow Coma Scale score of 12 or less, who had a CT scan showing an intracranial abnormality consistent with trauma, and were within eight hours of their injury were randomly allocated to low, medium or high dose Anatibant or to placebo. Outcomes were Serious Adverse Events (SAE), mortality 15 days following injury and in-hospital morbidity assessed by the Glasgow Coma Scale (GCS), the Disability Rating Scale (DRS) and a modified version of the Oxford Handicap Scale (HIREOS). RESULTS 228 patients out of a planned sample size of 400 patients were randomised. The risk of experiencing one or more SAEs was 26.4% (43/163) in the combined Anatibant treated group, compared to 19.3% (11/57) in the placebo group (relative risk = 1.37; 95% CI 0.76 to 2.46). All cause mortality in the Anatibant treated group was 19% and in the placebo group 15.8% (relative risk 1.20, 95% CI 0.61 to 2.36). The mean GCS at discharge was 12.48 in the Anatibant treated group and 13.0 in the placebo group. Mean DRS was 11.18 Anatibant versus 9.73 placebo, and mean HIREOS was 3.94 Anatibant versus 3.54 placebo. The differences between the mean levels for GCS, DRS and HIREOS in the Anatibant and placebo groups, when adjusted for baseline GCS, showed a non-significant trend for worse outcomes in all three measures. CONCLUSION This trial did not reach the planned sample size of 400 patients and consequently, the study power to detect an increase in the risk of serious adverse events was reduced. This trial provides no reliable evidence of benefit or harm and a larger trial would be needed to establish safety and effectiveness. TRIAL REGISTRATION This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN23625128.

Effect of a general school-based physical activity intervention on bone mineral content and density: A cluster-randomized controlled trial.

Background: Specific physical loading leads to enhanced bone development during childhood. A general physical activity program mimicking a real-life situation was successful at increasing general physical health in children. Yet, it is not clear whether it can equally increase bone mineral mass. We performed a cluster-randomized controlled trial in children of both gender and different pubertal stages to determine whether a school-based physical activity (PA) program during one school-year influences bone mineral content (BMC) and density (BMD), irrespective of gender.Methods: Twenty-eight 1st and 5th grade (6-7 and 11-12 year-old) classes were cluster randomized to an intervention (INT, 16 classes, n = 297) and control (CON; 12 classes, n = 205) group. The intervention consisted of a multi-component PA intervention including daily physical education with at least 10 min of jumping or strength training exercises of various intensities. Measurements included anthropometry, and BMC and BMD of total body, femoral neck, total hip and lumbar spine using dual-energy X-ray absorptiometry (DXA). PA was assessed by accelerometers and Tanner stages by questionnaires. Analyses were performed by a regression model adjusted for gender, baseline height and weight, baseline PA, post-intervention pubertal stage, baseline BMC, and cluster.Results: 275 (72%) of 380 children who initially agreed to have DXA measurements had also post-intervention DXA and PA data. Mean age of prepubertal and pubertal children at baseline was 8.7 +/- 2.1 and 11.1 +/- 0.6 years, respectively. Compared to CON, children in INT showed statistically significant increases in BMC of total body, femoral neck, and lumbar spine by 5.5%, 5.4% and 4.7% (all p < 0.05), respectively, and BMD of total body and lumbar spine by 8.4% and 7.3% (both p < 0.01), respectively. There was no gender*group, but a pubertal stage*group interaction consistently favoring prepubertal children.Conclusion: A general school-based PA intervention can increase bone health in elementary school children of both genders, particularly before puberty. (C) 2010 Elsevier Inc. All rights reserved.

Prospective multicenter study of the impact of carbapenem resistance on mortality in Pseudomonas aeruginosa bloodstream infections.

The impact of antimicrobial resistance on clinical outcomes is the subject of ongoing investigations, although uncertainty remains about its contribution to mortality. We investigated the impact of carbapenem resistance on mortality in Pseudomonas aeruginosa bacteremia in a prospective multicenter (10 teaching hospitals) observational study of patients with monomicrobial bacteremia followed up for 30 days after the onset of bacteremia. The adjusted influence of carbapenem resistance on mortality was studied by using Cox regression analysis. Of 632 episodes, 487 (77%) were caused by carbapenem-susceptible P. aeruginosa (CSPA) isolates, and 145 (23%) were caused by carbapenem-resistant P. aeruginosa (CRPA) isolates. The median incidence density of nosocomial CRPA bacteremia was 2.3 episodes per 100,000 patient-days (95% confidence interval [CI], 1.9 to 2.8). The regression demonstrated a time-dependent effect of carbapenem resistance on mortality as well as a significant interaction with the Charlson index: the deleterious effect of carbapenem resistance on mortality decreased with higher Charlson index scores. The impact of resistance on mortality was statistically significant only from the fifth day after the onset of the bacteremia, reaching its peak values at day 30 (adjusted hazard ratio for a Charlson score of 0 at day 30, 9.9 [95% CI, 3.3 to 29.4]; adjusted hazard ratio for a Charlson score of 5 at day 30, 2.6 [95% CI, 0.8 to 8]). This study clarifies the relationship between carbapenem resistance and mortality in patients with P. aeruginosa bacteremia. Although resistance was associated with a higher risk of mortality, the study suggested that this deleterious effect may not be as great during the first days of the bacteremia or in the presence of comorbidities.

Effect of statin therapy in the outcome of bloodstream infections due to Staphylococcus aureus: a prospective cohort study.

INTRODUCTION Statins have pleiotropic effects that could influence the prevention and outcome of some infectious diseases. There is no information about their specific effect on Staphylococcus aureus bacteremia (SAB). METHODS A prospective cohort study including all SAB diagnosed in patients aged ≥18 years admitted to a 950-bed tertiary hospital from March 2008 to January 2011 was performed. The main outcome variable was 14-day mortality, and the secondary outcome variables were 30-day mortality, persistent bacteremia (PB) and presence of severe sepsis or septic shock at diagnosis of SAB. The effect of statin therapy at the onset of SAB was studied by multivariate logistic regression and Cox regression analysis, including a propensity score for statin therapy. RESULTS We included 160 episodes. Thirty-three patients (21.3%) were receiving statins at the onset of SAB. 14-day mortality was 21.3%. After adjustment for age, Charlson index, Pitt score, adequate management, and high risk source, statin therapy had a protective effect on 14-day mortality (adjusted OR = 0.08; 95% CI: 0.01-0.66; p = 0.02), and PB (OR = 0.89; 95% CI: 0.27-1.00; p = 0.05) although the effect was not significant on 30-day mortality (OR = 0.35; 95% CI: 0.10-1.23; p = 0.10) or presentation with severe sepsis or septic shock (adjusted OR = 0.89; CI 95%: 0.27-2.94; p = 0.8). An effect on 30-day mortality could neither be demonstrated on Cox analysis (adjusted HR = 0.5; 95% CI: 0.19-1.29; p = 0.15). CONCLUSIONS Statin treatment in patients with SAB was associated with lower early mortality and PB. Randomized studies are necessary to identify the role of statins in the treatment of patients with SAB.

Prospective multicenter study of the impact of carbapenem resistance on mortality in Pseudomonas aeruginosa bloodstream infections.

The impact of antimicrobial resistance on clinical outcomes is the subject of ongoing investigations, although uncertainty remains about its contribution to mortality. We investigated the impact of carbapenem resistance on mortality in Pseudomonas aeruginosa bacteremia in a prospective multicenter (10 teaching hospitals) observational study of patients with monomicrobial bacteremia followed up for 30 days after the onset of bacteremia. The adjusted influence of carbapenem resistance on mortality was studied by using Cox regression analysis. Of 632 episodes, 487 (77%) were caused by carbapenem-susceptible P. aeruginosa (CSPA) isolates, and 145 (23%) were caused by carbapenem-resistant P. aeruginosa (CRPA) isolates. The median incidence density of nosocomial CRPA bacteremia was 2.3 episodes per 100,000 patient-days (95% confidence interval [CI], 1.9 to 2.8). The regression demonstrated a time-dependent effect of carbapenem resistance on mortality as well as a significant interaction with the Charlson index: the deleterious effect of carbapenem resistance on mortality decreased with higher Charlson index scores. The impact of resistance on mortality was statistically significant only from the fifth day after the onset of the bacteremia, reaching its peak values at day 30 (adjusted hazard ratio for a Charlson score of 0 at day 30, 9.9 [95% CI, 3.3 to 29.4]; adjusted hazard ratio for a Charlson score of 5 at day 30, 2.6 [95% CI, 0.8 to 8]). This study clarifies the relationship between carbapenem resistance and mortality in patients with P. aeruginosa bacteremia. Although resistance was associated with a higher risk of mortality, the study suggested that this deleterious effect may not be as great during the first days of the bacteremia or in the presence of comorbidities.

Effect of age on toxicokinetics among human volunteers exposed to propylene glycol methyl ether (PGME)

Aging adults represent the fastest growing population segment in many countries. Physiological and metabolic changes in the aging process may alter how aging adults biologically respond to pollutants. In a controlled human toxicokinetic study (exposure chamber; 12 m³), aging volunteers (n=10; >58 years) were exposed to propylene glycol monomethyl ether (PGME, CAS no. 107-98-2) at 50 ppm for 6 h. The dose-dependent renal excretion of oxidative metabolites, conjugated and free PGME could potentially be altered by age. AIMS: (1) Compare PGME toxicokinetic profiles between aging and young volunteers (20-25 years) and gender; (2) test the predictive power of a compartmental toxicokinetic (TK) model developed for aging persons against urinary PGME concentrations found in this study. METHODS: Urine samples were collected before, during, and after the exposure. Urinary PGME was quantified by capillary GC/FID. RESULTS: Differences in urinary PGME profiles were not noted between genders but between age groups. Metabolic parameters had to be changed to fit the age adjusted TK model to the experimental results, implying a slower enzymatic pathway in the aging volunteers. For an appropriate exposure assessment, urinary total PGME should be quantified. CONCLUSION: Age is a factor that should be considered when biological limit values are developed.

The effect of environment on development and survival of pupae of the necrophagous fly Ophyra albuquerquei Lopes (Diptera, Muscidae)

The effect of environment on development and survival of pupae of the necrophagous fly Ophyra albuquerquei Lopes (Diptera, Muscidae). Species of Ophyra Robineau-Desvoidy, 1830 are found in decomposing bodies, usually in fresh, bloated and decay stages. Ophyra albuquerquei Lopes, for example, can be found in animal carcasses. The influence of environmental factors has not been evaluated in puparia of O. albuquerquei. Thus, the focus of this work was motivated by the need for models to predict the development of a necrophagous insect as a function of abiotic factors. Colonies of O. albuquerquei were maintained in the laboratory to obtain pupae. On the tenth day of each month 200 pupae, divided equally into 10 glass jars, were exposed to the environment and checked daily for adult emergence of each sample. We concluded that the high survival rate observed suggested that the diets used for rearing the larvae and maintaining the adults were appropriate. Also, the data adjusted to robust generalized linear models and there were no interruptions of O. albuquerquei pupae development within the limits of temperatures studied in southern Rio Grande do Sul, given the high survival presented.

Adverse events to antiretrovirals in the Swiss HIV Cohort Study: effect on mortality and treatment modification.

BACKGROUND: Antiretroviral therapy (ART) decreases morbidity and mortality in HIV-infected patients but is associated with considerable adverse events (AEs). METHODS: We examined the effect of AEs to ART on mortality, treatment modifications and drop-out in the Swiss HIV Cohort Study. A cross-sectional evaluation of prevalence of 13 clinical and 11 laboratory parameters was performed in 1999 in 1,078 patients on ART. AEs were defined as abnormalities probably or certainly related to ART. A score including the number and severity of AEs was defined. The subsequent progression to death, drop-out and treatment modification due to intolerance were evaluated according to the baseline AE score and characteristics of individual AEs. RESULTS: Of the 1,078 patients, laboratory AEs were reported in 23% and clinical AEs in 45%. During a median follow up of 5.9 years, laboratory AEs were associated with higher mortality with an adjusted hazard ratio (HR) of 1.3 (95% confidence interval [CI] 1.2-1.5; P < 0.001) per score point. For clinical AEs no significant association with increased mortality was found. In contrast, an increasing score for clinical AEs (HR 1.11,95% CI 1.04-1.18; P = 0.002), but not for laboratory AEs (HR 1.07, 95% CI 0.97-1.17; P = 0.17), was associated with antiretroviral treatment modification. AEs were not associated with a higher drop-out rate. CONCLUSIONS: The burden of laboratory AEs to antiretroviral drugs is associated with a higher mortality. Physicians seem to change treatments to relieve clinical symptoms, while accepting laboratory AEs. Minimizing laboratory drug toxicity seems warranted and its influence on survival should be further evaluated.

Neurally adjusted ventilatory assist can improve arterial oxygenation

INTRODUCTION. Neurally Adjusted Ventilatory Assist (NAVA) [1] is a new spontaneousassisted ventilatory mode which uses the diaphragmatic electrical activity (Eadi) to pilot the ventilator. Eadi is used to initiate the ventilator's pressurization and cycling off. Delivered inspiratory assistance is proportional to Eadi. NAVA can improve patient-ventilator synchrony [2] compared to pressure support (PS), but little is known about its effect on minute ventilation and oxygenation. OBJECTIVES. To compare the effects of NAVA and PS on minute ventilation and oxygenation and to analyze potential determinant factors for oxygenation. METHODS. Comparison between two 20-min periods under NAVA and PS. NAVA gain (proportionality factor between Eadi and delivered pressure) set as to obtain the same peak pressure as in PS. FIO2 and positive end-expiratory pressure (PEEP) were the same in NAVA and PS. Blood gas analyses were performed at the end of both recording periods. Statistical analysis: groups were compared with paired t tests or non parametric Wilcoxon signed-rank tests. p\0.05 was considered significant. RESULTS. [Mean ± SD]: 22 patients (age 66 ± 12 year, 7 M/15F, BMI 23.4 ± 3.1 kg/m2), 8 patients with COPD. Initial settings: PS 13 ± 3 cmH2O, PEEP 7 ± 2 cmH2O, NAVA gain 2.2 ± 1.8. Minute ventilation and PaCO2 were the same with both modes (p = 0.296 and 0.848, respectively). Tidal volume was lower with NAVA (427 ± 102 vs. 477 ± 102 ml, p\0.001). In contrast respiratory rate was higher with NAVA (25.6 ± 9.5 vs. 22.3 ± 8.9 cycles/min). Arterial oxygenation was improved with NAVA (PaO2 85.1 ± 28.9 vs. 75.8 ± 11.9 mmHg, p = 0.017, PaO2/FIO2 210 ± 53 vs. 195 ± 58 mmHg, p = 0.019). Neural inspiratory time (Tin) was comparable between NAVA and PS (p = 0.566). Among potential determinant factors for oxygenation, mean airway pressure (Pmean) was lower with NAVA (10.6 ± 2.6 vs. 11.1 ± 2.4 cmH2O, p = 0.006), as was the pressure time product (PTP) (6.8 ± 3.0 vs. 9.2 ± 3.5 cmH2O 9 s, p = 0.004). There were less asynchrony events with NAVA (2.3 ± 2.0 vs. 4.4 ± 3.8, p = 0.009).Tidal volume variability was higher with NAVA (variation coefficient: 30 ± 19.5 vs. 13.5 ± 8.6, p\0.001). Inspiratory time in excess (Tiex) was lower with NAVA (56 ± 23 vs. 202 ± 200 ms, p = 0.001). CONCLUSION. Despite lower Pmean and PTP in NAVA, arterial oxygenation was improved compared to PS. As asynchronies may be associated with an increased work of breathing and a higher oxygen consumption, their decrease in number with NAVA could be an explanation for oxygenation improvement. Another explanation could be the increase in VT variability. Further studies should now be performed to confirm the potential of NAVA in improving arterial oxygenation and explore the underlying mechanisms.

Effect of age toxicokinetics among human volunteers exposed to propylene glycol monomethyl ether (PGME)

Rationale: Aging adults represent the fastest growing population segment in many countries. Physiological and metabolic changes in the aging process may alter how aging adults respond to exposures compared to younger workers. Current preventive workplace exposure measures may therefore not be sufficiently protective for the aging workforce. In a controlled human toxicokinetic study (exposure chamber; 12m3), the volunteers (n=11) were men and women over the age of 58 years and exposed to a commonly used, low neurotoxic glycol ether; PGME (CAS no. 107-98- 2) (50 ppm, 6 hours). Oxidative metabolism (Michaelis-Menten) is the major pathway and conjugation the minor in humans. Metabolites, conjugated and free PGME are eliminated through the kidneys, and the elimination kinetics is dose-dependent (0 order). Scope: (1) compare the toxicokinetic profile of PGME obtained in the aging volunteers (58- 62 years) to young volunteers (20-25 years) from a previous study; (2) Test the predictive power of an existing PGME toxicokinetic compartment model for aging persons against urinary PGME concentrations found in volunteers from our experimental study. Experimental procedure: Urine samples were collected before, every 2-hour during exposures for six hours, and ad-lib for additional 20 hours. Urinary analysis of free and total PGME was performed using capillary GC/FID. The toxicokinetic model (Berkley Madonna software) was ageadjusted. Results. Urinary free and total PGME concentration rose rapidly, and did not reach an apparent plateau level during exposure. Less conjugation was observed in the older group. The predictive model developed for the young group predicted well total PGME in the aging group but not free PGME. The age adjusted toxicokinetic model's Vmax1 had to be changed for the aging group, implying slower enzymatic pathway. Conclusion: The toxicokinetic model did not predict well if only the physiological parameters were adjusted for aging adults (existing model); a substance specific metabolic rate parameter was also needed.

Fat oxidation in nonobese and obese adolescents: effect of body composition and pubertal development.

OBJECTIVES: To measure postabsorptive fat oxidation (F(ox)) and to assess its association with body composition (lean body mass [LBM] and body fat mass [BFM]) and pubertal development. DESIGN: We studied 235 control (male/female ratio = 116/119; age [mean +/- SD]: 13.1 +/- 1.7 years; weight: 45.3 +/- 10.5 kg; LBM: 34.3 +/- 7.1 kg; BFM: 11.0 +/- 4.5 kg) and 159 obese (male/female ratio = 93/66; age: 12.9 +/- 2.1 years; weight: 76.2 +/- 19.1 kg; LBM: 47.4 +/- 10.9 kg; BFM: 28.8 +/- 9.2 kg) adolescents. Postabsorptive F(ox) was calculated from oxygen consumption, carbon dioxide production, and urinary nitrogen as measured by indirect calorimetry and Kjeldahl's method, respectively. Body composition was determined by anthropometry. RESULTS: Postabsorptive F(ox) (absolute value and percentage of resting metabolic rate) was significantly (p < 0.001) higher in the obese adolescents (76.7 +/- 26.3 gm/24 hours, 42.3% +/- 18.7%) than in the control subjects (40.0 +/- 26.3 gm/24 hours, 28.7% +/- 17.0%), even if adjusted for LBM. F(ox) corrected for BFM was similar in control and in obese children, but was significantly lower in girls compared with boys (control male subjects: 62.1 +/- 29.1 gm/24 hours, control female subjects: 51.6 +/- 28.4 gm/24 hours, obese male subjects: 57.3 +/- 29 gm/24 hour, obese female subjects: 45.0 +/- 28.4 gm/24 hours). BFM and LBM showed a significant positive correlation with F(ox). By stepwise regression analysis the most important determinant of F(ox) was BFM in obese and LBM in control children. There was a significant rise in F(ox) during puberty; however, it was mainly explained by changes in body composition. CONCLUSIONS: Obese adolescents have higher F(ox) rates than their normal-weight counterparts. Both LBM and fat mass are important determinants of F(ox).