A 26-week 20(S)-ginsenoside Rg3 oral toxicity study in Beagle dogs.

20(s)-ginsenoside Rg3 is a red ginseng-derived compound with the formula C42H72O13 that has been increasingly used by humans, leading to safety concerns regarding this use. In the current study, we conducted a 26-week study during which 20(S)-ginsenoside Rg3 (0, 7, 20, or 60 mg/kg) was continuously administered orally to Beagle dogs in order to explore its toxicity in these animals, with control dogs receiving a vehicle capsule. In total, 10 dogs received each dose of this compound (n = 5 male, n = 5 female per dose). Animals were continuously monitored for a 26-week administration period and a subsequent 4-week follow-up recovery period. At the end of study, we observed no evidence of 20(S)-ginsenoside Rg3 toxicity in clinical indications, body weight, food intake, ophthalmoscopy, electrocardiogram, urinalysis, hematology, serum biochemistry, gross and histopathology findings. However, the kidney relative weight of animals receiving 60 mg/kg of compound was significantly elevated relative to control animals (5.15 ±â€¯0.88‰ vs. 4.11 ±â€¯0.59‰. P < 0.05), and this effect was reversed after 4-week recovery period. Based on these results, the NOAEL value for orally administered 20(S)-ginsenoside Rg3 in dogs is 20 mg/kg.

Repeated sub-chronic oral toxicity study of xylooligosaccharides (XOS) in dogs.

In this study, Beagle dogs were administered xylooligosaccharide (XOS, CAS # 87099-0) at doses of 0, 1250, 2500, and 5000 mg/kg/day by oral gavage for 26 weeks. A 4-week recovery period was added to observe delayed or reversible toxicity. Measurements included body weight, food consumption, clinical observations, temperature, electrocardiogram (ECG), urinalysis, blood chemistry, hematology, organ weight, gross necropsy, and histopathological examination. Except for transient diarrhea or vomiting, no treatment-related adverse effects were noted. In the mid-dose groups, transitional diarrhea was observed in the initial 1-2 weeks. In the high-dose groups, diarrhea and/or vomiting were observed episodically over the duration of treatment. However, they disappeared after XOS was withdrawn in the recovery period. Although there was a tendency toward less weight gain in the high-dose group animal group, this is typical in animals and humans fed non-digestible carbohydrates. This chronic toxicity study demonstrated that the no observed adverse effect level (NOAEL) of XOS is 2500 mg/kg body weight (BW)/day. Based on body surface area (conversion factor of 0.54 for dogs to human), this corresponds to daily doses of 1350 mg/kg BW or 81-108 g XOS in human adults weighing 60-80 kg.

Ready-to-Eat Cereal Consumption with Total and Cause-Specific Mortality: Prospective Analysis of 367,442 Individuals.

BACKGROUND: Intakes of ready-to-eat cereal (RTEC) have been inversely associated with risk factors of chronic diseases such as cardiovascular disease (CVD), type 2 diabetes, and certain cancers; however, their relations with total and cause-specific mortality remain unclear. OBJECTIVE: To prospectively assess the associations of RTEC intakes with all causes and disease-specific mortality risk. DESIGN: The study included 367,442 participants from the prospective National Institutes of Health (NIH)-AARP Diet and Health Study. Intakes of RTEC were assessed at baseline. RESULTS: Over an average of 14 years of follow-up, 46,067 deaths were documented. Consumption of RTEC was significantly associated with reduced risk of mortality from all-cause mortality and death from CVD, diabetes, all cancer, and digestive cancer (all p for trend < 0.05). In multivariate models, compared to nonconsumers of RTEC, those in the highest intake of RTEC had a 15% lower risk of all-cause mortality and 10%-30% lower risk of disease-specific mortality. Within RTEC consumers, total fiber intakes were associated with reduced risk of mortality from all-cause mortality and deaths from CVD, all cancer, digestive cancer, and respiratory disease (all p for trend < 0.005). CONCLUSIONS: Consumption of RTEC was associated with reduced risk of all-cause mortality and mortality from specific diseases such as CVD, diabetes, and cancer. This association may be mediated via greater fiber intake.

Effects of 14 Versus 21 Days of Nimodipine Therapy on Neurological Outcomes in Aneurysmal Subarachnoid Hemorrhage Patients.

BACKGROUND: Oral nimodipine is standard therapy for patients suffering an aneurysmal subarachnoid hemorrhage (aSAH). During a national drug shortage, nimodipine therapy was shortened from a 21-day course to a 14-day course at our institution. OBJECTIVE: The objective of this study was to compare neurological outcomes among patients who had previously received the standard duration of therapy compared with those who received a shortened duration as a result of the national drug shortage. METHODS: This retrospective cohort study evaluated adult patients receiving nimodipine for aSAH from January 2012 to August 2013. Neurological outcome, graded by Modified Rankin Scale (mRS) at hospital discharge, was compared between patients receiving a shortened course and those receiving the standard duration of nimodipine. RESULTS: A total of 199 aSAH patients were included in the analysis. There were 164 patients in the standard-duration and 35 patients in the shortened-duration group. Baseline patient severity of illness, assessed by SAPS II (Simplified Acute Physiology Score), and severity of aSAH, assessed by Fisher grade, and Hunt and Hess grade scores, did not differ between the treatment groups. A shortened duration of nimodipine was not associated with a higher risk of a poor neurological outcome defined by mRS (odds ratio = 1.85; 95% CI = 0.54-6.32; P = 0.32). Mortality rates were similar between the groups. CONCLUSIONS: A 14-day course of nimodipine therapy was not associated with worse neurological outcomes in aSAH patients at one institution. More studies are needed prior to recommending a shortened duration of nimodipine therapy in all aSAH patients.

Consumption of whole grains and cereal fiber and total and cause-specific mortality: prospective analysis of 367,442 individuals.

BACKGROUND: Intakes of whole grains and cereal fiber have been inversely associated with the risk of chronic diseases; however, their relation with total and disease-specific mortality remain unclear. We aimed to prospectively assess the association of whole grains and cereal fiber intake with all causes and cause-specific mortality. METHODS: The study included 367,442 participants from the prospective NIH-AARP Diet and Health Study (enrolled in 1995 and followed through 2009). Participants with cancer, heart disease, stroke, diabetes, and self-reported end-stage renal disease at baseline were excluded. RESULTS: Over an average of 14 years of follow-up, a total of 46,067 deaths were documented. Consumption of whole grains were inversely associated with risk of all-cause mortality and death from cancer, cardiovascular disease (CVD), diabetes, respiratory disease, infections, and other causes. In multivariable models, as compared with individuals with the lowest intakes, those in the highest intake of whole grains had a 17% (95% CI, 14-19%) lower risk of all-cause mortality and 11-48% lower risk of disease-specific mortality (all P for trend <0.023); those in the highest intake of cereal fiber had a 19% (95% CI, 16-21%) lower risk of all-cause mortality and 15-34% lower risk of disease-specific mortality (all P for trend <0.005). When cereal fiber was further adjusted, the associations of whole grains with death from CVD, respiratory disease and infections became not significant; the associations with all-cause mortality and death from cancer and diabetes were attenuated but remained significant (P for trend <0.029). CONCLUSIONS: Consumption of whole grains and cereal fiber was inversely associated with reduced total and cause-specific mortality. Our data suggest cereal fiber is one potentially protective component.

Erratum: Consumption of whole grains and cereal fiber and total and cause-specific mortality: prospective analysis of 367,442 individuals.

This is an Erratum to BMC Medicine 2015, 13:59, highlighting previously undeclared competing interests and including more information in the acknowledgements section.Please see related article: http://www.biomedcentral.com/1741-7015/13/59. The statement in the competing interests should read as follows: This study is funded by unrestricted research fund from NutraSource. Susan Cho is founder and owner of NutraSource and Albert Lee is an employee of NutraSource. The other authors declare that they have no competing interests. The following information should be included in the acknowledgements section: The authors also thank Dr. Yi K Park at National Cancer Institute for her guidance in the study design.

Association between phosphorus intake and bone health in the NHANES population.

The objective of this study was to estimate the independent associations between intake of phosphorus (P) and bone health parameters such as bone mineral content (BMC) and bone mineral density (BMD). It provides odds ratio (OR) of osteoporosis with quartiles of P intake adjusted for covariates (i.e., age, gender, BMI, and consumption of calcium (Ca), protein, total dairy foods, and vitamin D as well as intakes of supplemental Ca, vitamin D, and multivitamins/minerals). Data came from males and females aged 13-99 years who participated in the 2005-2010 National Health and Nutrition Examination Survey (NHANES). Analyses showed that higher P intake was associated with higher Ca intake, and that dietary Ca:P ratios (0.51-0.62, with a mean of 0.60 for adults) were adequate in all age/gender groups. High intake of P was positively associated with BMC in female teenagers (Q4 vs. Q1: BMC, 30.9 ± 1.1 vs. 29.0 ± 0.5 g, P = 0.001). It was also positively associated with BMC and BMD as well as reduced risk of osteoporosis in adults >20 years of age (Q4 vs. Q1: OR of osteoporosis, 0.55; 95% confidence interval [CI], 0.39- 0.79; P = 0.001; BMC, 37.5 ± 0.4 vs. 36.70 ± 0.3 g, P < 0.01; BMD, 0.986 ± 0.004 vs. 0.966 ± 0.005 g/cm(2), P < 0.05). The data suggest that high intake of P has no adverse effect on bone metabolism in populations with adequate Ca intake, and that it is also associated with positive bone parameters in some age/gender groups.

A subchronic toxicity study, preceded by an in utero exposure phase, with refined arachidonic acid-rich oil (RAO) derived from Mortierella alpina XM027 in rats.

To evaluate the potential toxicity of refined arachidonic acid-rich oil (RAO) derived from Mortierella alpina (M. alpina) XM027, we performed a 90-day subchronic study in F1 Sprague Dawley (SD) rats. This study was preceded by a 4-week pretreatment period of parental (F0) rats and exposure of the F0 dams throughout mating, gestation, and lactation. The results indicated that RAO, at dose levels of 0.5%, 1.5%, and 5%, did not affect either reproductive performance of the parental rats, or any characteristics of the pups. In the subchronic study with the offspring (F1) rats, no treatment related abnormalities were observed. In summary, no observable adverse effect level (NOAEL) in this study was placed at 5% RAO, the highest level tested. This level corresponds to approximately 3750mg/kg in F0 females, 2850mg/kg in F0 males, 4850mg/kg in F1 females, and 4480mg/kg in F1 males.

Consumption of whole grains is associated with improved diet quality and nutrient intake in children and adolescents: the National Health and Nutrition Examination Survey 1999-2004.

OBJECTIVE: To examine the association of consumption of whole grains (WG) with diet quality and nutrient intake in children and adolescents. DESIGN: Secondary analysis of cross-sectional data. SETTING: The 1999-2004 National Health and Nutrition Examination Survey. SUBJECTS: Children aged 2-5 years (n 2278) and 6-12 years (n 3868) and adolescents aged 13-18 years (n 4931). The participants were divided into four WG consumption groups: ≥ 0 to < 0·6, ≥ 0·6 to < 1·5, ≥ 1·5 to < 3·0 and ≥ 3·0 servings/d. Nutrient intake and diet quality, using the Healthy Eating Index (HEI)-2005, were determined for each group from a single 24 h dietary recall. RESULTS: The mean number of servings of WG consumed was 0·45, 0·59 and 0·63 for children/adolescents at the age of 2-5, 6-12 and 13-18 years, respectively. In all groups, HEI and intakes of energy, fibre, vitamin B6, folate, magnesium, phosphorus and iron were significantly higher in those consuming ≥ 3·0 servings of WG/d; intakes of protein, total fat, SFA and MUFA and cholesterol levels were lower. Intakes of PUFA (6-12 years), vitamins B1 (2-5 and 13-18 years), B2 (13-18 years), A (2-5 and 13-18 years) and E (13-18 years) were higher in those groups consuming ≥ 3·0 servings of WG/d; intakes of added sugars (2-5 years), vitamin C (2-5 and 6-12 years), potassium and sodium (6-12 years) were lower. CONCLUSIONS: Overall consumption of WG was low. Children and adolescents who consumed the most servings of WG had better diet quality and nutrient intake.

Relationship between whole grain and fiber consumption and body weight measures among 6- to 18-year-olds.

OBJECTIVES: To examine the relationship between whole grain and fiber consumption and body weight measures in children 6 to 12 (n=3868) and adolescents 13 to 18 (n=4931) years old. STUDY DESIGN: Combined 1999 to 2004 National Health and Nutrition Examination Survey data were analyzed. Mean body mass index (BMI), BMI percentile, BMI z-score, waist circumference, and prevalence of overweight/obesity were compared across categories of whole grain consumption (0 to <0.6, >or=0.6 to <1.5, >or=1.5 to <3, and >or=3 servings) with (1) a sex, ethnicity, and total energy intake-adjusted model and (2) a cereal fiber plus model 1 covariates profile. RESULTS: Mean whole grain intake was 0.59 and 0.63 servings/d among children 6 to 12 years and adolescents 13 to 18 years, respectively. In children, consumption of >or=3 servings of whole grain was not associated with body weight measures; however, consumption of 1.5 to <3 servings was positively associated with all weight measures. In adolescents, BMI z-score was significantly lower in the highest whole grain consumption group compared with the lowest 2 groups; BMI percentile and waist circumference (model 1 only) were also significantly lower in the highest whole grain consumption group. CONCLUSIONS: Overall consumption of whole grain was below current recommendations of at least 3 servings per day. Only in adolescents was this level of whole grain intake associated with lower BMI z-scores.

Repeated-dose 26-week oral toxicity study of ginsenoside compound K in Beagle dogs.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginsenoside compound K (CK), a product produced by the intestinal bacteria-mediated breakdown of ginsenoside, exhibits a wide array of pharmacological activities against diverse targets. However, few of preclinical safety evaluation of CK is reported. AIMS OF THE STUDY: The present study therefore sought to assess the toxicity of oral CK in Beagle dogs over a 26-week period. MATERIAL AND METHODS: All dogs received 4, 12, or 36 mg/kg oral CK doses for 26 weeks with regular monitoring, followed by a 4-week recovery period. Animals were monitored through measurements of temperature, weight, food intake, blood chemistry and hematological findings, electrocardiogram (ECG) measurements, urinalysis, gross necropsy and organ weight and tissue histopathology. RESULTS: Animals in the 36 mg/kg group exhibited an apparent reduction in body weight over the study period, in addition to the presence of focal liver necrosis and increased plasma enzyme levels (alanine aminotransferase, ALT; alkaline phosphatase, ALP) consistent with hepatotoxicity, although there was some evidence suggesting this toxicity was reversible. Animals in the 4 and 12 mg/kg groups did not exhibit any apparent toxicity for any measured parameters. CONCLUSION: These results thus indicate that the no observed adverse effect level (NOAEL) in dogs is 12 mg/kg.

Preclinical safety of ginsenoside compound K: Acute, and 26-week oral toxicity studies in mice and rats.

Ginsenoside compound K (CK) is a hydrolysate of ginsenosides in the soil bacteria. This study evaluated the toxicity of CK as acute and the 26-week repeated-dose. The results of acute toxicity show that CK administered orally to rats and mice did not cause mortality or toxicity at the maximum dosage of 8 g/kg and 10 g/kg, respectively. In the toxicity study for 26-week, rats were administered with CK at doses of 13, 40, or 120 mg/kg, and were observed for 26 weeks and recovery periods of four weeks. Under the conditions, asthenia, hypoactivity, loss of fur and body weight reduction were transiently noticed in males of 120 mg/kg group. Hepatotoxicity and nephrotoxicity also were evident including the elevation of liver and kidney relative weight, along with focal liver necrosis as well as the increase in plasma enzymes (ALT and ALP) in male rats receiving CK (120 mg/kg), but this toxicity might be reversible. For 13 and 40 mg/kg CK groups, there was no significant variation in food habits, clinical signs, urine analysis, body weight, biochemical and hematological values, organ coefficient and histopathology examination. The NOAEL for male and female rats were observed to be 40 and 120 mg/kg, respectively.

Ready-to-eat breakfast cereal consumption enhances milk and calcium intake in the US population.

BACKGROUND: Inadequate intake of calcium-rich foods among US adults and children is a public health concern. Fluid milk is one of the best calcium sources because of its bioavailability and its versatility as both a beverage and a complement to various solid foods. One of the foods commonly consumed with milk is ready-to-eat breakfast cereal (RTEC). OBJECTIVE: We aimed to establish the association between the intake of RTEC, milk, and calcium within the context of the most current population dietary practices. We hypothesized that RTEC consumption facilitates milk consumption and is associated with adequacy of calcium intake in the US population. DESIGN: The most recent National Health and Nutrition Examination Survey, 1999-2000, data set was used as the source of data for this research. SUBJECTS/SETTING: US subjects aged 4 years and older (n=7,403), excluding pregnant and/or lactating women. Data were stratified according to sex and age (4 to 8 years, 9 to 13 years, 14 to 18 years, 19 to 30 years, 31 to 50 years, 51 to 70 years, and 71+ years), and then by consumption of breakfast, RTEC, and milk. STATISTICAL ANALYSES PERFORMED: SAS (release 8.1, 2000, SAS Institute Inc, Cary, NC) and SUDAAN (release 8.0.2, 2003, Research Triangle Institute, Research Triangle Park, NC) were used to calculate sample weighted means, standard errors, and population percentages. Multiple regression and multiple logistic regression models, with controls for covariates, were used to determine the predictability of total calcium intake from breakfast consumption compared to breakfast nonconsumption, and from inclusion of RTEC and milk in the breakfast meal compared with breakfast meal content without RTEC and milk. RESULTS: RTEC was predominantly consumed at breakfast. Average calcium intake at breakfast was seven times greater when RTEC was consumed with milk than when RTEC was consumed without milk. In multiple regression analyses, breakfast consumption, and milk consumption with or without RTEC all strongly predicted total daily calcium intake (P<0.05) while controlling for covariates. The percentage of respondents below the Adequate Intake level for calcium was higher for non-RTEC breakfast consumers than for RTEC breakfast consumers in all age-sex categories except those older than age 70 years, and girls aged 9 to 13 years. CONCLUSIONS: Consumption of RTEC at breakfast was associated with greater daily intake of both milk and calcium in all age and sex groups in the US population.

The Effect of Hyponatremia and Sodium Variability on Outcomes in Adults with Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Hyponatremia is common in patients with subarachnoid hemorrhage, but its effect on outcomes remains contentious. Fluctuation in sodium has been reported to negatively affect perioperative outcomes in general surgical patients, but not specifically in patients with a subarachnoid hemorrhage. The primary aim was to describe the relationship between 1) hyponatremia and 2) sodium fluctuations during intensive care and neurologic outcome at hospital discharge. METHODS: Adults with aneurysmal subarachnoid hemorrhage between January 2012 and September 2013 were retrospectively reviewed. Data were collected for admission to day 14 of intensive care or death. Severity of illness was assessed by Hunt and Hess grade and simplified acute physiology score. Hyponatremia was defined as any measurement <135 mEq/L. Sodium variability was categorized as a maximum change of <6, 6-12, or >12 mEq/L during intensive care. Neurologic outcomes at discharge were assessed by modified Rankin Scale. The relationship between sodium and outcome was assessed by ordinal logistic regression. RESULTS: A total of 198 patients were included. After adjustment for Hunt and Hess grade, severity of systemic illness, patient age, surgical intervention, and whether or not the hyponatremia was treated with additional sodium, hyponatremia was not associated with worse neurologic outcomes. More patients with sodium variability of 6-12 and >12 mEq/L had cerebral infarction than those with variability <6 mEq/L and had modified Rankin Scale scores of 2-3 and 4-6, respectively (P = 0.001). CONCLUSIONS: Sodium fluctuation, not hyponatremia, is associated with worse neurologic outcome in patients with aneurysmal subarachnoid hemorrhage. This is in contradistinction to current teaching and warrants further examination.

Is consumption of breakfast associated with body mass index in US adults?

OBJECTIVE: To test the hypothesis that breakfast consumption is associated with weight status measured by body mass index in US adults. DESIGN: Analyses of data from the National Health and Nutrition Examination Survey, 1999-2000. PARTICIPANTS/SETTING: Men and women aged > or = 19 years (N=4,218), excluding pregnant and/or lactating women. STATISTICAL ANALYSES PERFORMED: SAS (release 8.1, 2000, SAS Institute Inc, Cary, NC) and SUDAAN (release 8.0.2, 2003, Research Triangle Institute, Research Triangle Park, NC) software were used to calculate sample-weighted means, standard errors, and population percentages of breakfast consumers. Multiple logistic and linear regression models, with controls for covariates, were used to determine the predictability of body mass index from breakfast consumption and from inclusion of ready-to-eat cereal (RTEC) in the breakfast meal. RESULTS: Breakfast consumers were more likely than breakfast nonconsumers to be older, female, white, nonsmokers, regular exercisers, and trying to control their weight. For women, daily energy intake was higher among breakfast consumers than among breakfast nonconsumers; for both men and women, energy intake from fat among RTEC breakfast consumers was significantly lower than among non-RTEC breakfast consumers, whereas energy from carbohydrate among RTEC breakfast consumers was significantly higher than among non-RTEC breakfast consumers. For women, the odds ratios for BMI > or = 25 were lower for breakfast consumers (odds ratio = 0.76) and RTEC breakfast consumers (odds ratio = 0.70) compared with breakfast nonconsumers and non-RTEC breakfast consumers, respectively, after adjusting the models for covariates. When RTEC consumption was added as a covariate, breakfast consumers no longer exhibited significantly lower odds ratios compared with breakfast nonconsumers. Furthermore, regression analyses supported an inverse association between RTEC breakfast consumption and body mass index in women (regression coefficient = -0.37, P<.01) after adjusting for covariates. CONCLUSIONS: When we document the association of breakfast consumption with lower prevalence of overweight and obesity, types of meal should be considered as an important determinant. RTEC breakfast consumption, associated with a desirable macronutrient profile for preventing obesity, predicted weight status in women, but not in men. In addition to sex difference in the association of breakfast consumption and RTEC breakfast consumption with lower prevalence of overweight, the effects of physiological variables and health-related behaviors on the relationship between total and RTEC intake at breakfast and weight status, remain to be established.

A subchronic dietary toxicity study of rice hull fiber in rats.

We conducted a 90-day feeding study to investigate subchronic toxicity of rice hull fiber. Sprague Dawley rats were randomly divided into four groups; each received a diet containing 0%, 2.5%, 3.75% and 5.0% (w/w) rice hull fiber for 90days. Clinical observations were carried out daily, with weekly measurements of body weight and food consumption. We performed ophthalmic and histological examinations at termination. Blood and urine samples were collected to measure hematology and clinical chemistry parameters. No mortality, ophthalmic abnormalities, or adverse treatment-related effects were seen during clinical observations, hematological tests, or analyses of urine. Macroscopic or microscopic examinations of organs revealed no treatment related abnormalities. The only treatment related significant changes were reduced concentrations of fasting blood glucose (up to 17.6%) and cholesterol (up to 22.0%), typical benefits of dietary fiber, in males treated with 3.75 and 5% rice hull fiber. The no-observed-adverse-effect-level (NOAEL) for rice hull fiber was 5.0% for both genders (females, 3.80g/kg body weight/day; males, 4.11g/kg body weight/day).

Consumption of cereal fiber, mixtures of whole grains and bran, and whole grains and risk reduction in type 2 diabetes, obesity, and cardiovascular disease.

BACKGROUND: Studies of whole grain and chronic disease have often included bran-enriched foods and other ingredients that do not meet the current definition of whole grains. Therefore, we assessed the literature to test whether whole grains alone had benefits on these diseases. OBJECTIVE: The objective was to assess the contribution of bran or cereal fiber on the impact of whole grains on the risk of type 2 diabetes (T2D), obesity and body weight measures, and cardiovascular disease (CVD) in human studies as the basis for establishing an American Society for Nutrition (ASN) position on this subject. DESIGN: We performed a comprehensive PubMed search of human studies published from 1965 to December 2010. RESULTS: Most whole-grain studies included mixtures of whole grains and foods with ≥25% bran. Prospective studies consistently showed a reduced risk of T2D with high intakes of cereal fiber or mixtures of whole grains and bran. For body weight, a limited number of prospective studies on cereal fiber and whole grains reported small but significant reductions in weight gain. For CVD, studies found reduced risk with high intakes of cereal fiber or mixtures of whole grains and bran. CONCLUSIONS: The ASN position, based on the current state of the science, is that consumption of foods rich in cereal fiber or mixtures of whole grains and bran is modestly associated with a reduced risk of obesity, T2D, and CVD. The data for whole grains alone are limited primarily because of varying definitions among epidemiologic studies of what, and how much, was included in that food category.

Improved vancomycin dosing in children using area under the curve exposure.

BACKGROUND: : Our objectives were to (1) determine the pharmacokinetic indices of vancomycin in pediatric patients; and (2) compare attainment of 2 target exposures: area under curve (AUC) / minimum inhibitory concentration (MIC) ≥400 and trough concentration ≥15 mcg/mL. METHODS: : The population-based pharmacokinetic modeling was performed using NONMEM 7.2 for children ≥3 months old who received vancomycin for ≥48 hours from 2003 to 2011. A 1-compartment model with first-order kinetics was used to estimate clearance, volume of distribution and AUC. Empiric Bayesian post hoc individual parameters and Monte Carlo simulations (N = 11,000) were performed. RESULTS: : Analysis included 702 patients with 1660 vancomycin serum concentrations. Median age was 6.6 (interquartile range 2.2-13.4) years, weight 22.7 (12.6-46) kg and baseline serum creatinine 0.40 (0.30-0.60) mg/dL. Final model pharmacokinetic indices were clearance (L/h) = 0.248 * Wt * (0.48/serum creatinine) * (ln(age)/7.8) and volume of distribution (L) = 0.636 * Wt. Using these parameters and the observed MIC distribution, Monte Carlo simulation indicated that the initial median dose of 44 (39-52) mg/kg/day was inadequate in most subjects. Regimens of 60 mg/kg/day for subjects ≥12 years old and 70 mg/kg/day for those <12 years old achieved target AUC/MIC in ~75% and trough concentrations ≥15 in ~45% of virtual subjects. An AUC/MIC ~400 corresponded to trough concentration ~8 to 9 mcg/mL. CONCLUSIONS: : Targeted exposure using vancomycin AUC/MIC, compared with trough concentrations, is a more realistic target in children. Depending on age, serum creatinine and MIC distribution, vancomycin in a dosage of 60 to 70 mg/kg/day was necessary to achieve AUC/MIC ≥ 400 in 75% of patients.

The soluble fiber NUTRIOSE induces a dose-dependent beneficial impact on satiety over time in humans.

Strong evidence supports the ability of dietary fibers to improve satiety. However, large variations in the physical and chemical characteristics of dietary fiber modulate the physiologic responses. We hypothesized that a nonviscous soluble dietary fiber may influence satiety. This randomized, double-blind, placebo-controlled clinical study in 100 overweight healthy adults in China investigated the effect of different dosages of dietary supplementation with a dextrin, NUTRIOSE (ROQUETTE frères, Lestrem, France), on short-term satiety over time. Subjects were randomized by body mass index and energy intake and then assigned to receive either placebo or 8, 14, 18, or 24 g/d of NUTRIOSE mixed with orange juice (n = 20 volunteers per group). On days -2, 0, 2, 5, 7, 14, and 21, short-term satiety was evaluated with a visual analog scale, and hunger feeling status was assessed with Likert scale. NUTRIOSE exhibits a progressive and significant impact on short-term satiety, which is time and dosage correlated. Some statistical differences appear for the group 8 g/d from day 5, and from day 0 for the groups 14, 18, and 24 g/d. The hunger feeling status decreases significantly from day 5 to the end of the evaluation for the group 24 g and from day 7 for the groups 14 and 18 g. By day 5, the group 24 g showed significantly longer time to hunger between meals compared with placebo. These results suggest that dietary supplementation with a soluble fiber can decrease hunger feeling and increase short-term satiety over time when added to a beverage from 8 to 24 g/d with time- and dose-responses relationship.

Whole grain and fiber consumption are associated with lower body weight measures in US adults: National Health and Nutrition Examination Survey 1999-2004.

This study examined the association of whole grain consumption with body weight measures and prevalence of overweight/obesity in a recent, nationally representative sample of adults. A secondary analysis of 1999-2004 National Health and Nutrition Examination Survey (NHANES) data was conducted using adults 19 to 50 years of age (y) (n = 7,039) and 51+ y (n = 6,237). Participants were categorized by whole grain consumption: ≥ 0 to <0.6, ≥ 0.6 to <1.5, ≥ 1.5 to <3.0, and ≥ 3.0 servings/day. Main outcome measures included body mass index (BMI), waist circumference (WC), and prevalence of overweight/obesity. Sample weights were applied and the number and percentages of adults in whole grain consumption groups were determined. Least-square means and standard errors were calculated for body weight measures. Two regression models were developed and compared. Model 1 covariates included age, gender, ethnicity, and total energy intake; Model 2 was extended to include cereal fiber. Trend analysis was conducted to test for differences between least-square means. Significance was set at P ≤ .05. Adults 19-50 and 51+ y consumed a mean of 0.63 and 0.77 servings of whole grains/day, respectively. A significant trend was observed in both age groups for increased consumption of whole grains with lower BMI, WC, and percentage overweight/obese (Model 1); however, a significant trend was not observed when cereal fiber was added as a covariate (Model 2). Results confirm overall whole grain intake well below recommendations, and adults who consumed the most servings of whole grains had lower body weight measures. Results also suggest that fiber in whole grain foods may mediate associations with weight measures in adults. Intake of whole grain foods should be encouraged by health professionals.