Valoración de la exposición a plaguicidas en cultivos extensivos de la Argentina y su potencial impacto sobre la salud / Pesticides exposure assessment in extensive crops in Argentina and their potential impact on health

A nivel nacional no hay descripciones espaciales o analíticas para el diagnóstico deexposición a plaguicidas.ObjetivosDescribir la distribución espacial de la exposición a plaguicidas en Argentina y suasociación con indicadores de carga de cáncer. Construir índices incorporando prácticaslaborales y de vida, y validarlos con biomarcadores y salud de sujetos laboralmenteexpuestos y sus familias.MétodosPara describir la distribución espacial de la exposición y su asociación con indicadoresde carga de cáncer se construyeron dos índices globales: de exposición a plaguicidas(IEP) y de impacto ambiental total (IIAT). Se estudiaron sus distribuciones espaciales,y mediante un estudio ecológico nacional se analizó la asociación con las tasas demortalidad de cáncer total, mama y próstata. Otros dos índices de exposición construidoscon información individual de agroaplicadores de Córdoba fueron validados a partir deluso de resultados de biomarcadores (actividad de butirilcolinestrasa y genotoxicidad)y de salud de sujetos laboralmente expuestos; y se compararon con sus respectivoscontroles. Por último, se analizaron las condiciones de salud de niños de esas familias.ResultadosEl área pampeana agrupa IEP mayores al promedio nacional. Los mayores IIAT fueronpara 2,4-D y clorpirifos en igual zona. Los altos IIAT de cipermetrina y clorpirifos seasocian con más mortalidad de cáncer de mama; los de glifosato y clorimuron, conla de cáncer total en varones. Los síntomas generales, cardiorrespiratorios, dérmicosy daño genotóxico fueron mayores en aplicadores, pero no se asocian a niveles deexposición. Los niños presentan síntomas irritativos en un 30%; más de la mitad estánexpuestos a aplicaciones, vive a menos de 500 metros de depósitos y van a escuelas a500 metros de campos fumigados. Un 20% asiste en tareas de campo, sin elementosde protección personal ni cobertura de obra social

Updated cost-effectiveness analysis of supplemental glutamine for parenteral nutrition of intensive-care patients.

BACKGROUND/OBJECTIVES: Intravenous (i.v.) glutamine supplementation of parenteral nutrition (PN) can improve clinical outcomes, reduce mortality and infection rates and shorten the length of hospital and/or intensive care unit (ICU) stays compared with standard PN. This study is a pharmacoeconomic analysis to determine whether i.v. glutamine supplementation of PN remains both a highly favourable and cost-effective option for Italian ICU patients. SUBJECTS/METHODS: A previously published discrete event simulation model was updated by incorporating the most up-to-date and clinically relevant efficacy data (a clinically realistic subgroup analysis from a published meta-analysis), recent cost data from the Italian health-care system and the latest epidemiology data from a large Italian ICU database (covering 230 Italian ICUs and more than 77,000 patients). Sensitivity analyses were performed to test the robustness of the results. RESULTS: Parenteral glutamine supplementation can significantly improve ICU efficiency in Italy, as the additional cost of supplemented treatment is more than completely offset by cost savings in hospital care. Supplementation was more cost-effective (cost-effectiveness ratio (CER)=[euro ]35,165 per patient discharged alive) than standard, non-supplemented PN (CER=[euro ]40,156 per patient discharged alive), and it resulted in mean cost savings of [euro ]4991 per patient discharged alive or [euro ]1047 per patient admitted to the hospital. Sensitivity analyses confirmed the robustness of these results. CONCLUSIONS: Alanyl-glutamine supplementation of PN is a clinically and economically attractive strategy for ICU patients in Italy and may be applicable to selected ICU patient populations in other countries.

Pesquisa de trastornos alimentarios en jóvenes con diabetes tipo 1: estudio comparativo con población normal / Screening of eating disorders in adolescents with type 1 diabetes: a comparative study with a normal control group

Objetivo Pesquisar Trastornos alimentarios (TA) en fase preclínica en jóvenes con Diabetes Mellitus Insulinodependiente (DMID), comparar los resultados con población control (PC) sana del estudio de la Sociedad Argentina de Pediatría (SAP) Identificar la asociación con factores metabólicos y medio-ambientales. Métodos: Entre 12/2001 y 8/2003 pediatras diabetólogos de 13 centros del país encuestaron a 270 pacientes con DMID de ambos sexos de 10 a 19a. Se utilizaron como instrumentos el EDEQ (Questionary Eating Disorders Examination), modificado con 40 preguntas y 5 subescalas, para detectar pacientes sospechosos de TA y el EDE12 para la confirmación diagnóstica. El diagnóstico de TA se basó en el DSM-IV. Se tomó una encuesta demográfica y control metabólico de los pacientes diabéticos y se evaluó antropometría (Peso, Talla, Índice de Masa Corporal (IMC)). Los resultados se compararon con 1971 controles del estudio de la SAP evaluados de igual forma. Se aplicó Chi2, test de T, Test de Fisher, Anova. Un valor de p <0.05 se consideró significativo. Se utilizó el programa EpiInfo 6.04. Resultados: El 26.5% (72/270) fue sospechoso de tener TA vs. 19.2% (380/1971) de la PC (p=0.001). Encontramos 20% de varones diabéticos sospechosos que, comparados con la PC (12%) fue mayor (p=0.001). Encontramos mayor proporción de sospechosos entre las post-menárquicas (p 0.006), los pacientes con antecedentes de problemas alimentarios (p=0.001) y los que presentaron un IMC superior al Plo.90 (p=0.03). Completó el EDE-12 el 78% de los sospechosos (56/72) confirmando TA el 94.6% (53/56). Estos pacientes presentaron trastorno alimentario no especificado (TANE). De ellos, 48 (91%) llenaron criterio de trastorno compulsivo del comer (BED). No se diagnosticó ni anorexia nerviosa (AN) ni Bulimia nerviosa (BN). 15% (11) de los sospechosos manipuló insulina. La prevalencia de sobrepeso fue de 18.8% en diabéticos vs. 26.3% en PC (p NS) Conclusión: La frecuencia de sospecha de TA así como el diagnóstico de formas subclínicas es mayor que la encontrada en la PC y la citada por la literatura. El equipo tratante deberá estar alerta en especial en las púberes postmenárquicas, los pacientes con antecedentes de problemas alimentarios y aquellos con alto IMC (AU)

Objective: To screen eating disorders (ED) in the pre-clinical phase in adolescents with insulin-dependent diabetes mellitus (IDDM), to compare the results with a healthy control group (CG) of the Sociedad Argentina de Pediatría (SAP) study, and to identify associated metabolic and environmental factors. Methods: Between 12/2001 and 8/2003 pediatricians specialized in diabetes from 13 centers in Argentina interviewed 270 male and female patients with IDDM between 10 and 19 years. The QEDE (Questionnaire Eating Disorders Examination) was used, modified with 40 questions and 5 subscales, to detect patients with possible ED and the EDE12 to confirm the diagnosis. The diagnosis of ED was made using the DSM-IV. Demographic and anthropometric data (weight, height, body mass index (BMI)) were registered and the patients were metabolically controlled. The results were compared with the data of 1971 controls from the SAP study that were similarly assessed. Chi square test, T test, Fisher test, and Anova were used for the statistical analysis. A p value of <0.05 was considered significant. EpiInfo 6.04 was used. Results: Of the patients, 26.5% (72/270) was suspected of having an ED vs. 19.2% (380/1971) of the CG (p=0.001). Of the male IDDM patients, 20% was suspected of having an ED compared to 12% of the CG (p=0.001). We found a higher rate of suspected cases among post-menarche girls (p 0.006), patients with a history of eating disturbances (p=0.001), and those who had a BMI greater than the 90th percentile (p=0.03). Of the patients suspected of having an ED, 78% (56/72) filled out the EDE-12, confirming the ED in 94.6% of the cases (53/56). These patients presented with non-specified eating disorders (NOSED). Forty-eight 48 (91%) met the criteria of binge-eating disorder (BED). Neither anorexia nervosa (AN) nor bulimia nervosa (BN) was diagnosed. Fifteen percent (11) of those suspected having an ED manipulated insulin. The prevalence of overweight was 18.8% among the IDDM patients vs. 26.3% in the CG (p NS). Conclusion: Suspicion of ED and sub-clinical forms of ED was more frequent in the IDDM group than in the CG or than mentioned in the literature. The treating team should specially be alert in post-menarche adolescents, patients with a history of eating disturbances, and in those with a high BMI (AU)

Hospital management of complicated intra-abdominal infections: pharmacoeconomic evaluation.

Complicated intra-abdominal infections (cIAIs) represent a heavy burden for the italian National Health System (NHS) and the italian society, with estimated annual costs of 1.5 and 3 billion euros, respectively. Both monotherapy and antibiotic combinations induce significantly different acquisition and administration costs but substantially equivalent therapeutic results, with average clinical effectiveness rates of 70-80%. this apparent equivalence presumably depends on the widespread trend to individualize the therapeutic strategy according to the clinical severity and the community or nosocomial origin of cIAIs, as well as to the degree of non-appropriateness when empirically choosing a first-line antibiotic.The average cost of nosocomial management of cIAI patients depends on several factors: posology, antibiotic drug acquisition, administration costs, duration of therapy, mix of antibiotic schedules, rates of the therapeutic failures, prolonged hospitalization. The introduction of a new antibiotic like tigecycline to the therapeutic arsenal leads to a small increase in average antibiotic acquisition and treatment costs per patient: this increase is proportional to the percentage of patients treated with the new antibiotic. According to a decisional model, implemented on international outcome data and italian costs, the mean cost for first-line antibiotic acquisition and the mean cost for first- and second-line antibiotic treatment represent respectively only 2% and 8% of the mean overall hospitalization cost. the mean hospitalization cost estimated by the model is noticeably higher than the mean value of Diagnosis Related Group (DRG) tariffs presumably reimbursed by the italian NHS to hospitals for ciAi-related hospitalizations. Greater overall efficiency levels in the nosocomial management of cIAI patients are achievable mainly through the reduction of non-appropriateness rates in first-line antibiotic choices and better treatment individualization, possible if the physician is offered the choice of as many valid therapeutic options as possible, in order to guarantee the best possibility of cure for each patient.

Cost-effectiveness and healthcare budget impact in Italy of inhaled corticosteroids and bronchodilators for severe and very severe COPD patients.

Current practice guidelines for the treatment of COPD recommend the use of combined inhaled corticosteroids and long-acting bronchodilators in severe and very severe patients (GOLD stages III and IV). The aim of this study was to evaluate, through a simulation model, the economic consequences of this recommendation in Italy. We developed a cost-effectiveness analysis (CEA) on five alternative therapeutic strategies (salmeterol/fluticasone, SF; formoterol! budesonide, FB; salmeterol alone, S; fluticasone alone, F; control, C). Published data on the Italian COPD population and efficacy data from international reference trials were fitted in a disease progression model based on a Markov chain representing severity stages and death. The yearly total direct costs of treating COPD patients in Italy was estimated at approximately Euro 7 billion, with a mean cost per patient per year of around Euro 2450. Mean survival of the cohort is 11.5 years. The C and F strategies were dominated (ie, are associated with worse outcomes and higher costs) by all alternatives. SF and FB were the most effective strategies, with a slight clinical superiority of SF, but they were also marginally more expensive than S. Incremental cost-effectiveness of SF vs S was Euro 679.5 per avoided exacerbation and Euro 3.3 per symptom-free day. Compared with current practice, the recommended use of combined inhaled corticosteroids and long-acting bronchodilators for severe and very severe COPD patients has the potential for improving clinical outcomes without increasing healthcare costs.

Betahistine in the treatment of vertiginous syndromes: a meta-analysis.

Vertigo is a very frequent disorder, associated with highly disabling symptomatology. Since the aetiology cannot always be easily identified, treatment is often addressed to the symptoms. Betahistine, a drug characterized by a multi-factorial mode of action of the modulatory type, has been widely employed in the management of various vertiginous syndromes. Its use in Italy is, currently, authorized to treat the vertiginous symptoms related to Ménière's disease. A meta-analysis has, therefore, been carried out to assess, the efficacy of betahistine in the treatment of other vertiginous syndromes, such as positional paroxysmal vertigo (cupulo-canalolithiasis) and vertigo secondary to arterial deficiency of the vertebrobasilar area, regardless of the specific cause. A review has been made of the literature concerning clinical trials performed with betahistine versus placebo in a randomised double-blind, parallel-group or cross-over design. Only studies evaluating betahistine in patients with vertiginous symptomatology not related to Ménière's disease were selected. Of the 104 publications, obtained from an analysis of "Medline", "EMBASE" and "CINAHL" databases, 7 clinical studies, which met the selection criteria, for a total of 367 patients, were extrapolated and analysed. The meta-analysis was conducted using the "Cochrane Collaboration's Review Manager" software in all the case series and in the sub-groups identified by the experimental design (parallel or crossover design), range of dosages (32-48 mg/day) and range of treatment duration (from 3 weeks to 4 months). The various parameters used to evaluate efficacy, adopted in the trials, and taken into account in the metaanalysis, as overall judgement of the patient or physician, number of vertiginous episodes and their duration, were classified according to the binary classification of "improved" and "not improved". The results of the meta-analysis confirm the therapeutic benefit of betahistine versus placebo. In particular, the investigation carried out on the overall sample shows an odds ratio of 3.52 (95% confidence interval 2.40-5.18) and a relative risk of 1.78 (95% confidence interval 1.48-2.13), while the analysis of the sub-groups denotes a maximum efficacy after doses of 32 to 36 mg and with a period of treatment of 3-8 weeks. The present meta-analysis confirms the benefit of drug treatment with betahistine for the vertiginous symptomatology related to cupulo-canalolithiasis and vertebro-basilar arterial insufficiency.

Cytotoxicity of anticancer drugs incorporated in solid lipid nanoparticles on HT-29 colorectal cancer cell line.

Solid lipid nanoparticles (SLN) carrying cholesteryl butyrate (chol-but), doxorubicin and paclitaxel had previously been developed, and the antiproliferative effect of SLN formulations versus conventional drug formulations was here evaluated on HT-29 cells. The 50% inhibitory concentration (IC(50) values were interpolated from growth curves obtained by trypan blue exclusion assay. In vitro cytotoxicity of SLN carrying chol-but (IC(50 72 h) 0.3 +/- 0.03 mM vs >0.6 mM) and doxorubicin (IC(50 72 h) 81.87 +/- 4.11 vs 126.57 +/- 0.72 nM) was higher than that of conventional drug formulations. Intracellular doxorubicin was double after 24 h exposure to loaded SLN versus the conventional drug formulation, at the highest concentration evaluated by flow cytometry. In vitro cytotoxicities of paclitaxel-loaded SLN and conventional drug formulation (IC(50 72 h) 37.36 +/- 6.41 vs 33.43 +/-1.17 nM) were similar. Moreover, the combination of low concentrations of chol-but SLN (0.1-0.2 mM) and doxorubicin (1.72 nM) or paclitaxel (1.17 nM) exerted a greater-than-additive antiproliferative effect at 24 h exposure, while the combination of Na-but and doxorubicin or paclitaxel did not. These preliminary in vitro results suggest that SLN could be proposed as alternative drug delivery system.

Recombinant Escherichia coli for the biomonitoring of benzene and its derivatives in the air.

For protection against environmental deterioration, pollutants should be reduced as much as possible. Therefore, a sensitive detection method for air pollutants is required, particularly for benzene, a compound with mutagenic, teratogenic, and carcinogenic properties. Some microorganisms have a number of enzymes that degrade organic compounds. The genetic information for many of these enzymes is codified in plasmids that usually comprise some elements such as proteins and RNA for their replication, and proteins for cell division control. Some plasmids have been obtained from Pseudomonas putida, a ubiquitous microorganism that is able to degrade biologic and inorganic compounds. P. putida contains the TOL plasmid, responsible for the degradation of benzene and its derivatives. The TOL plasmid has been fused with the gene for firefly luciferase (pTNS316 plasmid) to produce a luminescent bacterium (Escherichia coli HB101), which can be applied to the environmental monitoring of these chemicals. The recombinant E. coli transformed with the plasmid (E. coli HB101-pTNS316) was applied to the environmental biosensing of benzene and its derivatives. Measurement of bacteria-generated photons was done using a color-coded device to estimate quantitatively the pollutant concentration. The expression of luciferase was induced in the presence of aromatic compounds but the E. coli sensitivity has a detection limit: this bacterium dies if the benzene concentration is higher than 0.5 ppm and at this concentration the luminescence decreases so it is impossible to detect. Another limit for this biodevice is that the microorganism, very likely, accumulates the benzene and its derivatives, and therefore it is very important to consider the time of exposure. This biomonitor potentially offers a rapid, inexpensive, and sensitive technique for environmental detection of aromatic pollutant compounds.

Determination of disodium clodronate in human plasma and urine using gas-chromatography-nitrogen-phosphorous detections: validation and application in pharmacokinetic study.

We present a specific method for the determination of disodium clodronate in human plasma and urine using a gas-chromatographic system with nitrogen phosphorus detector (NPD). The compound was extracted from plasma and urine samples by an anion-exchange resin and derivatizated with bistrimethylsilyltrifluoroacetamide (BSTFA). Sodium bromobisphosphonate was used as internal standard. The calibration curves were linear in both plasma and urine, with a regression coefficient r > 0.9975 in plasma and r > 0.9977 in urine. The limit of quantitation was 0.3 microg/ml in plasma and 0.5 microg/ml in urine. The method was validated by intra-day assays at three concentration levels. During the study we carried out inter-day assays to confirm the feasibility of the method. The precision in plasma at 0.5, 15, and 45 microg/ml was 12.4, 0.2, and 6.5% (n = 40), respectively; in urine at 0.8, 8, and 40 microg/ml it was 8.6, 6.4, and 9.3% (n = 40), respectively. The method was accurate and reproducible, and was successfully applied to determine the pharmacokinetic parameters of clodronate in healthy volunteers after intravenous infusion and intramuscular injection of 200 mg of the compound. The Cmax after intravenous infusion and intramuscular injection was 16.1 and 12.8 microg/ml, respectively. AUC(0-48 h) after infusion administration and intramuscular injection was 44.2 +/- 18.0 and 47.5 +/- 12.4 h microg/ml, respectively. The elimination half-life in both administrations was 6.31 +/- 2.7 h.

Static and ELF magnetic fields enhance the in vivo anti-tumor efficacy of cis-platin against lewis lung carcinoma, but not of cyclophosphamide against B16 melanotic melanoma.

Previous works showed that exposure to static and extremely low frequency (ELF) magnetic fields (MF) over 3 mT slows down the growth kinetics of human tumors engrafted s.c. in immunodeficient mice, reducing their metastatizing power and prolonging mouse survival. In the experiments reported here, immunocompetent mice bearing murine Lewis Lung carcinomas (LLCs) or B16 melanotic melanomas were exposed to MF and treated respectively with two commonly used anti-cancer drugs: cis-diamminedichloroplatinum (cis-platin) and N,N-bis (2-chloroethyl)tetra-hydro-2H-1,3,2-oxazaphosphorin-2-amine 2-oxide (cyclophosphamide). The experiment endpoint was survival time. The survival time of mice treated with cis-platin (3mg/kg i.p.) and exposed to MF was significantly (P<0.01) longer than that of mice treated only with cis-platin or only exposed to MF, superimposing that of mice treated with 10mg/kg i.p. of the drug, showing that MF act synergically with the pharmacological treatment. On the contrary, when mice treated with cyclophosphamide (50mg/kg i.p.) were exposed to MF no synergic effects were observed, the survival curve being exactly the same as that of mice treated with the drug alone. No clinical signs or toxicity were seen in any of the mice exposed to MF alone or along with cis-platin or cyclophosphamide treatment, compared to mice given only the two known drugs.A possible explanation for the synergic effect of MF being found in mice treated with cis-platin could be that the platinum ion stimulates radical production and that MF enhance active oxygen production bringing about changes in tumor cell membrane permeability, influencing positively the drug uptake. Alternatively, or in addition to this, it has been demonstrated that the rate of conversion of cis-platin to reactive species able to bind to DNA, is increased by localized production of free radicals by MF.

Simultaneous HPLC determination of 5-fluorouracil and its metabolites in plasma of cancer patients.

5-Fluorouracil (5-Fu) is a commonly used anticancer agent for treatment of solid tumours. Certain studies have reported conflicting results between individual plasma concentration levels and toxicity or therapeutic effects. For this reasons some authors proposed to evaluate the plasma levels of 5-Fu metabolites 5-fluorouridine, 5-fluoro-2'-deoxyuridine and 5-fluoro-5,6-dihydro-uracil. The aim of the present work is to develop and validate a new HPLC method simultaneously determining 5-fluorouracil and its three metabolites, to be used to study the plasma levels, therapeutic effects and toxicity in cancer patients. The analytes were separated on a 4.6 x 250 mm ODS1 (5 micro m) not end-capped column, operating at room temperature. Elution was performed under isocratic conditions, employing a 1.5 mM K(3)PO(4) mobile phase (pH 5). 5-Bromo-5,6-dihydro-uracil was used as internal standard. The limits of quantitation were 0.5 micro g/mL for 5-fluorouracil, 1 micro g/mL for 5-fluoro-5,6-dihydro-uracil, 3 micro g/mL for 5-fluoro-2'-deoxyuridine and 5-fluorouridine; the stability, recovery, linearity, accuracy and specificity of the compounds were evaluated according to the criteria widely accepted. Using this method we measured plasma samples of 18 cancer patients treated with folinic acid (100 mg/m(2)) by intravenous administration, followed by an i.v. bolus of 5-Fu (400 mg/m(2)). The concentration levels of 5-fluorouracil and for 5-fluoro-5,6-dihydro-uracil were detectable in all the subjects while 5-fluorouridine and 5-fluoro-2'-deoxyuridine were present only in eight patients.

Plasma erythropoietin concentrations in patients receiving intensive platinum or nonplatinum chemotherapy.

AIMS: Platinum chemotherapy has been shown to have potent antineoplastic activity against various tumours, especially testicular, bladder, ovarian, head and neck cancers. This activity is accompanied by side-effects of nephrotoxicity and cumulative myelosuppression, the latter frequently presenting as severe anaemia. Cisplatin and carboplatin nephrotoxicity might lower erythropoietin (Epo) secretion and, by this mechanism, contribute to the anaemia that follows therapy with this chemotherapeutic agent. The aim of the present work is to study the plasma immunoerythropoietin and haemoglobin levels of cancer patients treated with platinum or 5-fluorouracil-based chemotherapy. METHODS: Plasma was obtained from 25 patients who were about to receive chemotherapy for advanced malignancy: 15 treated with cisplatin or carboplatin and 10 with nonplatinum drugs. Blood was collected on the first day (before drug administration) and around day 15 of every chemotherapy course. Complete blood count, creatinine and immunoreactive Epo levels were also measured in 22 healthy volunteers. RESULTS: An increase in Epo levels occurred following every course of 5-FU or platinum based chemotherapy in patients with steady concentrations of creatinine and decreased levels of haemoglobin (Hb). In particular, we observed an increase after about 15 days of the chemotherapy treatment and the Epo levels declined toward normal just before the following course. This phenomenon was evident in every course. CONCLUSIONS: Our results suggest that chemotherapy administration, using the current standards of hydration and forced diuresis, slightly lowered Hb levels but did not depress Epo production, both in 5-FU and in platinum treated subjects.

Determination of Ibuprofen in human plasma by high-performance liquid chromatography: validation and application in pharmacokinetic study.

A specific method for the simultaneous determination of S-(+)Ibuprofen and R-(-)Ibuprofen enantiomers in human plasma is described. Adopting a high-performance liquid chromatographic (HPLC) system with spectrofluorometer detector, the compounds were extracted from plasma in alcohol medium and were separated on C18 column, using a solution of acetonitrile-water-acetic acid-triethylamine as mobile phase. The limit of quantitation was 0.1 microg/mL for both compounds. The method was validated by intra-day assays at three concentration levels and was used in a kinetic study in healthy volunteers. During the study we carried out inter-day assays to confirm the feasibility of the method.

Economic impact of resistance in the community.

Antimicrobial resistance is assumed to be an important health problem and an economic burden to society. However, the relationship between the emergence of in vitro microbiological resistance and its clinical and socioeconomic consequences has not yet been satisfactorily determined for either nosocomial or community-acquired infection. In the case of both nosocomial and community-acquired infection, previous exhaustive reviews of published and unpublished reports concluded that mortality, likelihood of hospitalization, and length of hospital stay were usually at least twice as great for patients infected with drug-resistant strains as for those infected with drug-susceptible strains of the same bacteria. However, evaluation of the economic impact of resistance is still problematic and the adverse economic and health effects of drug-resistant bacterial infections can only be roughly quantified. Decision analysis models, such as decision trees, can aid evaluation of the impact of resistance on health and economic outcomes from the perspective of a given decision maker. A model of cost analysis should be based on a knowledge of the incremental consumption of resources specifically dependent on the dynamics of antimicrobial resistance in a given clinical setting (e.g. home care or hospital care). In general, we can assume that the increased rate of isolation of resistant strains from community-acquired infections correlates positively with an increase in morbidity, mortality, risk of hospitalization and the need for additional days in hospital and for more expensive and powerful antibiotics. We implemented and simulated a general decision-tree model to analyse the influence of antibiotic resistance on the economic outcomes of community-acquired lower respiratory tract infections, from the perspective of both society and the health-care local organization (HCLO). This model allows simulation of the impact of different degrees of resistance on the direct costs of an antibiotic therapy as well as on the cost-effectiveness of antibiotics with different degrees of resistance.

Pharmacoeconomic aspects of antibacterial treatment with cefotaxime.

Pharmacoeconomics is a relatively new discipline, which is becoming increasingly useful in the current climate of medical advances that continue despite limited access to healthcare resources. Pharmacoeconomics may be used as a tool, assisting healthcare decision makers to select clinically beneficial therapies and weigh clinical gain against expenditure. Cefotaxime has been shown in many studies to be a cost-effective antibiotic agent, its monetary value being augmented by its use in low dose, low frequency regimens. This cost-effectiveness, combined with a maintained broad spectrum of antibiotic activity, low propensity for selecting resistant bacterial strains and high therapeutic index, makes cefotaxime a suitable antibiotic agent in many indications involving mild-to-moderate infections by susceptible organisms.

Preliminary pharmacokinetic study of ibuprofen enantiomers after administration of a new oral formulation (ibuprofen arginine) to healthy male volunteers.

The pharmacokinetics of ibuprofen enantiomers were investigated in a crossover study in which seven healthy male volunteers received single oral doses of 800 mg racemic ibuprofen as a soluble granular formulation (sachet) containing L-arginine (designated trade name: Spedifen), 400 mg (-)R-ibuprofen arginine or 400 mg (+)S-ibuprofen arginine. Plasma levels of both enantiomers were monitored up to 480 minutes after drug intake using an enantioselective analytical method (HPLC with ultraviolet detection) with a quantitation limit of 0.25 mg/l. Substantial inter-subject variability in the evaluated pharmacokinetic parameters was observed in the present study. After (+)S-ibuprofen arginine, the following mean pharmacokinetic parameters +/-SD were calculated for (+)S-ibuprofen: tmax 28.6 +/- 28.4 min; Cmax 36.2 +/- 7.7 mg/l; AUC 86.4 +/- 14.9 mg.h/l; t1/2 105.2 +/- 20.4 min. After (-)R-ibuprofen arginine, the following mean pharmacokinetic parameters were calculated for (+)S-ibuprofen and (-)R-ibuprofen, respectively: tmax 90.0 +/- 17.3 and 50.5 +/- 20.5 min; Cmax 9.7 +/- 3.0 and 35.3 +/- 5.0 mg/l; AUC 47.0 +/- 17.2 and 104.7 +/- 27.7 mg.h/l; t1/2 148.1 +/- 63.6 and 97.7 +/- 23.3 min. After racemic ibuprofen arginine, the following mean pharmacokinetic parameters were calculated for (+)S- and (-)R-ibuprofen, respectively: tmax 30.7 +/- 29.1 and 22.9 +/- 29.8 min; Cmax 29.9 +/- 5.6 and 25.6 +/- 4.4 mg/l; AUC 105.1 +/- 23.0 and 65.3 +/- 15.0 mg.h/l; t1/2 136.6 +/- 20.7 and 128.6 +/- 45.0 min. Tmax values of S(+)- and (-)R-ibuprofen after a single dose of 400 mg of each enantiomer did not differ significantly from the corresponding parameters obtained after a single dose of 800 mg of racemic ibuprofen arginine, indicating that the absorption rate of (-)R- and (+)S-ibuprofen is not different when the two enantiomers are administered alone or as a racemic compound. An average of 49.3 +/- 9.0% of a dose of the (-)R-ibuprofen arginine was bioinverted into its antipode during the study period (480 minutes post-dosing). The percent bioinversion during the first 30 minutes after (-)R-ibuprofen arginine intake averaged 8.1 +/- 3.9%. The mean AUC of (+)S-ibuprofen calculated after 800 mg racemic ibuprofen arginine (105.1 +/- 23.0 mg.h/l) was lower than the mean AUC value obtained by summing the AUCs of (+)S-ibuprofen after administration of 400 mg (+)S-ibuprofen arginine and 400 mg (-)R-ibuprofen arginine (133.4 +/- 26.6 mg.h/l). In conclusion, the administration of Spedifen resulted in very rapid absorption of the (+)S-isomer (eutomer) with tmax values much lower than those observed for this isomer when conventional oral solid formulations such as capsules or tablets of racemic ibuprofen are administered. This characteristic is particularly favourable in those conditions in which a very rapid analgesic effect is required.