[Raman spectroscopy applied to analytical quality control of injectable drugs: analytical evaluation and comparative economic versus HPLC and UV / visible-FTIR]. / La spectroscopie Raman appliquée au contrôle de qualité analytique des médicaments injectables: évaluation analytique et économique comparative versus CLHP et uv/visible-iRTF.

In France, central IV admixture of chemotherapy (CT) treatments at the hospital is now required by law. We have previously shown that the shaping of Therapeutic Objects (TOs) could profit from an Analytical Quality Assurance (AQA), closely linked to the batch release, for the three key parameters: identity, purity, and initial concentration of the compound of interest. In the course of recent and diversified works, we showed the technical superiority of non-intrusive Raman Spectroscopy (RS) vs. any other analytical option and, especially for both HPLC and vibrational method using a UV/visible-FTIR coupling. An interconnected qualitative and economic assessment strongly helps to enrich these relevant works. The study compares in operational situation, the performance of three analytical methods used for the AQC of TOs. We used: a) a set of evaluation criteria, b) the depreciation tables of the machinery, c) the cost of disposables, d) the weight of equipment and technical installations, e) the basic accounting unit (unit of work) and its composite costs (Euros), which vary according to the technical options, the weight of both human resources and disposables; finally, different combinations are described. So, the unit of work can take 12 different values between 1 and 5.5 Euros, and we provide various recommendations. A qualitative evaluation grid constantly places the SR technology as superior or equal to the 2 other techniques currently available. Our results demonstrated: a) the major interest of the non-intrusive AQC performed by RS, especially when it is not possible to analyze a TO with existing methods e.g. elastomeric portable pumps, and b) the high potential for this technique to be a strong contributor to the security of the medication circuit, and to fight the iatrogenic effects of drugs especially in the hospital. It also contributes to the protection of all actors in healthcare and of their working environment.

Long-term efficacy and safety of a new olive oil-based intravenous fat emulsion in pediatric patients: a double-blind randomized study.

BACKGROUND: A new intravenous lipid emulsion (ILE) prepared from a mixture of soybean and olive oils contains only long-chain triacylglycerols, with a low proportion (20%) of polyunsaturated fatty acids and 60% monounsaturated fatty acids. OBJECTIVE: The goal of this randomized, double-blind clinical trial was to assess in children the efficacy and safety of this new ILE compared with a control group receiving a soybean-oil emulsion. DESIGN: Eighteen children received for 2 mo 24% of nonprotein energy (1.80 g kg (-)(1) d(-)(1)) either as the new ILE or a soybean oil-based emulsion. Assessments were performed on days -30, 0, 30, and 60 and the changes (day 60 - day 0) assessed by analysis of variance. RESULTS: There were no significant differences in triacylglycerol, apolipoproteins A-I and B, or HDL cholesterol between the 2 groups, whereas total and LDL cholesterol were higher in the soybean oil group on day 60. The pattern of 20:4n-6 in erythrocyte membranes did not change significantly, nor did the ratio of 20:3n-9 to 20:4n-6. On day 60, 18:1n-9 was significantly higher in the olive oil group, the ratio of Sigma(n)-6 > C(18) + 18:3n-6 to 18:2n-6 was 2.20 +/- 0.09 in the olive oil group and 1.33 +/- 0.16 in the soybean-oil group, and Sigma(n)-3 > C(18) was 3.83 +/- 0.30 in the olive oil group and 4. 03 +/- 0.33 in the soybean-oil group. The peroxidation index was lower after the olive oil treatment. CONCLUSIONS: The olive oil-based emulsion was well tolerated, maintained a normal EFA status, and may be more suitable for prevention of lipid peroxidation than the soybean-oil-based emulsion.

Home parenteral nutrition in children: bioavailability of vitamins in binary mixtures stored for 8 days.

Vitamin supply in children on long-term parenteral nutrition depends on the specific age-related needs and on the bioavailability of vitamins when introduced into nutritional bags. The present study aimed to investigate the vitamin status in children on home TPN receiving nutritional bags which had been stored during a prolonged period of 8 instead of 4 days and where the new vitamin preparation Cernevit has been introduced. 19 children aged from 5 months to 11 years receiving home parenteral nutrition, for 42 months on average, were studied. Daily vitamin supply for children above 2 years of age was: A 1050 ug, D 5.5 ug, E 10.2 mg plus 0.6 mg/g lipid (Intralipid), C 125 mg, B1 3.5 mg, B2 4.1 mg, B6 4.5 mg, biotine 69 mug; children who were younger than 2 years received half of these intakes. Water soluble vitamin status was only measured in children over 3 years old. Plasma levels remained stable and adequate for age, for most of the studied vitamins. Vitamin A concentration was inferior to 200 mug/l in 1 patient with hepatopathy. Plasma concentrations of vitamin E, which were initially below 6 mg/l in 4 patients, returned to normal during the study. Plasma levels of vitamin C were below 6.2 mg/l in several infants either temporarily (5 patients) or during the whole study period (2 patients). These results support a prolongation of the intervals between preparing batches of nutritional bags and also between deliveries. This results in a considerable reduction of costs, provided that plasma vitamin levels, specially vitamin C, are regularly monitored.

Inappropriate iron intake in children on long-term parenteral nutrition: outcome after iron withdrawal.

Inappropriate parenteral iron intake in children on long-term parenteral nutrition can be responsible for iron overload. This study was carried out to monitor iron status changes when iron parenteral intake was stopped in case of iron overload. Seven children with serum ferritin concentrations above 800 ng/ml (6 with documented liver iron overload) were prospectively studied after total discontinuation of parenteral iron intake and without chelation therapy. Iron status was assessed, by means of ferritin and iron plasma concentrations, 8-15 months (T(1)) and 24-30 months (T(2)) after withdrawal of parenteral iron. Ferritin and iron concentrations declined at T(1), or T(2) in all but two children. At T(2) ferritin and iron concentrations were significantly lower (P < 0.05) than before iron parenteral discontinuation with a yearly reduction of 22 +/- 15% and 15 +/- 16%, respectively, for ferritin concentration and iron concentration. This fall in serum ferritin concentration is comparable to thalassemic subjects after bone marrow transplantation. The total withdrawal of parenteral iron intake improves iron status in children with iron overload. Nevertheless, iron overload related parenteral nutrition should be avoided by lowering iron intake in case of long-term total parenteral nutrition and by careful monitoring.

Home parenteral nutrition in children: 8 years of experience with 112 patients.

It is essential that children on prolonged parenteral nutrition for anatomical or functional loss of small bowel should enjoy a quality of life which is as normal as possible. Their return home is a major factor in this. Over the past 8 years, 112 children were able to remain at home on cyclic parenteral nutrition. Forty-nine of them are no longer on home parenteral nutrition (HPN), 45 are still on HPN, and 18 have died. Growth and quality of life were good in most cases. Most of the complications were from infection, 1 septicaemia per 594 days on HPN. In the light of these results, HPN seems to be the best option for children requiring prolonged parenteral nutrition, although it can only be considered within the framework of a specialized centre, which ensures patient follow-up, and provides the logistical support required for this high-technology treatment.

Parenteral nutrition practices in hospital pharmacies in Switzerland, France, and Belgium.

OBJECTIVE: Important changes in administering total parenteral nutrition (PN) admixtures have occurred over the past decade. This study describes hospital pharmacists' practices in France (F), Switzerland (CH), and Belgium (B). METHODS: From the responses received using a standardized questionnaire, (n = 378) we determined the origin, types of container used, and choice of PN formula (standard versus tailor-made) and the type of quality control and the existence of nutrition support teams. RESULTS: The mean response rates were 55.6% (CH), 30.5% (F), and 24.5% (B). Standard formulas were used mainly for adult patients (CH, 86%; F, 79%; B, 86%), whereas approximately 50% of tailor-made PN bags were used for children. Single-compartment or multicompartment bags or glass bottles contained standard formulas. Most standard formulas were provided by industry, apart from (B), where 50% of PN solutions were compounded by hospital pharmacies. Single-compartment bags contained generally tailor-made formulas produced exclusively by hospital pharmacies in (CH) and (B), whereas 33% were provided by industry in (F). Quality controls were mostly visual and occurred in 75% to 95% of hospitals. Nutrition support teams were present in 32% to 45% of hospitals. CONCLUSION: The choice, origin, and type of container used for PN formulas were highly variable among countries. However, the use of standard formulas in bags was predominant in (CH) and (B). The function of nutrition support teams was similar in (F), (CH), and (B).

Effect of an elemental vs a complex diet on polyamine metabolism in rat isolated enterocytes.

BACKGROUND: Polyamines play an important role in the proliferation and differentiation of enterocytes. Ornithine decarboxylase (ODC) is the rate-limiting enzyme for polyamine biosynthesis. Elemental diets, providing easily absorbable nutrients such as free amino acids, are used in clinical practice to treat growth failure and malnutrition. They are very different from complex diets normally consumed. Little information is available about the influence of elemental diets on metabolic capacities of enterocytes. This study was undertaken in rats to assess the effects on polyamine metabolism of an elemental diet compared with a complex diet. METHODS: Rats were fed the elemental diet (group ED) or the control diet (group C) for 14 days. The dietary intakes were isocaloric and isonitrogenous in groups C and ED. Villous enterocytes were then isolated and metabolic capacities or enzyme activities were assessed. RESULTS: Both the enterocyte capacity to decarboxylate ornithine through ODC (measured in viable enterocytes) and ODC activity (measured in homogenates) were severely decreased in group ED. The polyamine content in enterocytes, however, was maintained at a similar level in both groups. This coincided with a decrease in the main enzymatic activity responsible for putrescine catabolism (ie, diamine oxidase activity) in group ED. CONCLUSIONS: Although nutrition manipulation was shown to alter polyamine biosynthesis in this study, the polyamine homeostasis was probably maintained, at least in part, through down-regulation of diamine oxidase.

Effect of an elemental vs a complex diet on L-citrulline production from L-arginine in rat isolated enterocytes.

BACKGROUND: L-Arginine and L-glutamine are highly metabolized by intestinal cells, leading to various metabolites, including L-citrulline, which is required for optimal growth. Elemental diets, used in clinical practice to treat growth failure and malnutrition, are very different from complex diets normally consumed. The aim of the present study was to assess the effects of an elemental diet compared with a complex diet on L-arginine metabolism in rat isolated enterocytes and its modulation by L-glutamine. METHODS: Rats were fed the elemental diet (group ED) or the control diet (group C) for 14 days. Villus enterocytes then were isolated, and metabolic capacities or enzyme activities were assessed. RESULTS: The incubation of enterocytes isolated from group C with 0.1 mmol/L L-[U-14C]-arginine led to the production of 125 +/- 25 pmol L-citrulline/10(6) cells per 30 minutes. This production showed a twofold increase in the presence of 2 mmol/L L-glutamine. In group ED, L-citrulline synthesis from L-arginine was markedly lower in the absence or in the presence of L-glutamine. This coincided with lower carbamoylphosphate synthase I activity and carbamoylphosphate (CP) content of enterocytes. Other L-arginine and L-glutamine metabolic pathways were not affected. Similar results were obtained when the elemental diet was administered continuously through a gastric catheter or fed by mouth. CONCLUSIONS: L-Glutamine favors the synthesis of L-citrulline from L-arginine in isolated enterocytes, probably via an increase in CP production. Changing the diet composition, from a complex to an elemental diet, results in an alteration of the enterocyte capacity to synthesize L-citrulline from L-arginine, irrespective of the rhythm of delivery.

[Optimized clinical use of vancomycin, a prospective observational study in a Paris teaching hospital]. / Optimisation de la prescription de la vancomycine : étude prospective observationnelle dans un centre hospitalo-universitaire parisien.

INTRODUCTION: Vancomycin is still the cornerstone of antibiotic therapy for patients with suspected or proven invasive methicillin resistant Staphylococcus aureus infections. However, clinical and pharmacodynamic studies underline that appropriate doses depend on the infection site, the patient's weight, his renal function, and the bacterial susceptibility. OBJECTIVE AND METHOD: In this prospective study made in a Paris teaching hospital, our two goals were to describe the modalities of infusion and serum concentration obtained during therapy, in our pediatrics and adults population. RESULTS: In our hospital, vancomycin was administered every eight hours in 83 % (97/102) of the cases and the doses used were 30 mg/kg per day in 67 % of cases (68/102). Serum trough levels reached 15 mcg/ml and 20 mcg/ml in 36 % and 18 % of cases respectively. Moreover, despite adequate doses, trough levels of 15 mcg/ml were obtained in only 40 % of cases. CONCLUSION: Vancomycin infusion use could be optimized, by defining optimal serum concentrations and monitoring made by a mobile team of infectious diseases specialists.

Prepubertal growth in children with long-term parenteral nutrition.

In children who depend on long-term parenteral nutrition (PN), a major goal is to obtain optimal growth. The aim of this retrospective study was to analyze growth in children on long-term cyclic nocturnal home PN, over at least 8 years before puberty. Nine boys and 7 girls were studied. Their mean age at the time of study was 11 years with a mean PN duration of 10.5 (8.6-16.4) years. Diseases were short bowel syndrome (5), intractable diarrhea (4), chronic intestinal pseudo-obstruction (4) and long segment Hirschsprung's disease (3). In each child, periods of at least 2 years were analyzed: either periods of regular growth (R: height gain >50th percentile), or slow growth (S: height gain < or =25th percentile). Results were expressed as mean +/- SD. Comparisons were performed using either Student's test for unpaired data or Wilcoxon's test for paired data. PN provided a mean of 224 +/- 80 mg nitrogen/kg/day and 43 +/- 14 kcal/kg/day equivalent to 50% of recommended supplies. At the time of study, the population presented with weight (W) = -0.7 +/- 0.8 SD and height (H) = -1.5 +/- 1.3 SD. The difference between W and expected W for H (W/H) was significant (p < 0.002). W/H ratio was 105 +/- 11%. For the total PN duration, weight gain was +0.2 +/- 1.5 SD and height loss was -0.75 +/- 1.4 SD. An excess weight gain occurred in parallel with the deflection of height gain. Of the 16 children, regular prepubertal growth was achieved in 4 only. The other 12 showed alternate periods of R and S. In 8 of them, 26.5 years of R and 33.5 years of S were compared, each child being his own control. PN nitrogen and energy supplies were significantly higher during R periods than during S periods. In the absence of any disease or treatment explaining the failure to thrive, inadequate PN supplies, especially in terms of nitrogen supply, are thought to be responsible for a negative nitrogen balance and slowed growth. In case of any deflection away from the individual growth curve, it is recommended to adjust the PN supply early, especially nitrogen supply.

Iron overload in children receiving prolonged parenteral nutrition.

This study was carried out to evaluate the iron status of 30 children aged 1 to 18 years who had been receiving total parenteral nutrition (TPN) for an average of 43 months with iron intakes of 100 micrograms/kg per day. Iron status was assessed by assaying the serum iron and ferritin levels and the transferrin saturation coefficient as a function of iron intake. Liver biopsy specimens were taken from 13 children. Twelve children had serum ferritin levels greater than 300 ng/ml, and 8 had levels greater than 800 ng/ml. The serum ferritin level and the transferrin saturation coefficient were positively correlated (r = 0.81; p < 0.01). The serum ferritin level was positively correlated with TPN duration and with the total iron intake (r = 0.68; p < 0.01). Of the 13 liver biopsy specimens, six showed signs of iron deposition. We conclude that there is a risk of iron overload in children receiving 100 micrograms iron per kilogram of body weight per day by TPN, indicating that intake should be reduced.