Hepatokine Profile in Adolescents with Polycystic Ovary Syndrome: A Case-Control Study.

The current guidelines suggest routine screening for non-alcoholic fatty liver disease (NAFLD) in patients with polycystic ovary syndrome (PCOS). Hepatokines seem to be promising surrogate endpoints for the diagnosis and severity of NAFLD. PCOS has its onset in adolescence and its metabolic sequalae begin during the same period. There are scarce data on the hepatokine profile of adolescent PCOS patients. This case-control study examined the serum profile of the hepatokines sex hormone-binding globulin (SHBG), selenoprotein P, fibroblast growth factor 21 (FGF21), and fetuin A in a sample of adolescent PCOS patients, and their association to metabolic and hormonal parameters. The selenoprotein P and SHBG serum concentrations were significantly decreased in PCOS patients vs. the controls (median (IQR), 2.47 (0.40) vs. 2.66 (0.36) µg/mL, p = 0.025; mean ± SD, 41.71 ± 19.41 vs. 54.94 ± 22.12 nmol/L, p = 0.011, respectively), whereas selenoprotein P was significantly and positively associated with testosterone (r = 0.325, p = 0.007) and the free androgen index (r = 0.361, p = 0.002). The SHBG demonstrated multiple significant negative correlations with adverse metabolic parameters. Among the PCOS patients, the FGF21 concentrations were significantly higher in those with NAFLD, whereas a 1 pg/mL increase in the FGF21 concentration increased the odds of NAFLD diagnosis by liver ultrasound by 1%, suggesting FGF21 as a potential biomarker for hepatic disease in females with PCOS in adolescence. Fetuin A was the least differentiated hepatokine between the PCOS patients and controls with the least associations with metabolic and hormonal parameters.

Pharmacokinetic Characteristics of Nebulized Colistimethate Sodium Using Two Different Types of Nebulizers in Critically Ill Patients with Ventilator-Associated Respiratory Infections.

Background: Rising antimicrobial resistance has led to a revived interest in inhaled colistin treatment in the critically ill patient with ventilator-associated respiratory infection (VARI). Nebulization via vibrating mesh nebulizers (VMNs) is considered the current standard-of-care, yet the use of generic jet nebulizers (JNs) is more widespread. Few data exist on the intrapulmonary pharmacokinetics of colistin when administered through VMNs, while there is a complete paucity regarding the use of JNs. Methods: In this study, 18 VARI patients who received 2 million international units of inhaled colistimethate sodium (CMS) through a VMN were pharmacokinetically compared with six VARI patients who received the same drug dose through a JN, in the absence of systemic CMS administration. Results: Surprisingly, VMN and JN led to comparable formed colistin exposures in the epithelial lining fluid (ELF) (median (IQR) AUC0-24: 86.2 (46.0-185.9) mg/L∙h with VMN and 91.5 (78.1-110.3) mg/L∙h with JN). The maximum ELF concentration was 10.4 (4.7-22.6) mg/L and 7.4 (6.2-10.3) mg/L, respectively. Conclusions: Based on our results, JN might be considered a viable alternative to the theoretically superior VMN. Therapeutic drug monitoring in the ELF can be advised due to the observed low exposure, high variability, and appreciable systemic absorption.

Systematic Review and Meta-Analysis of the Efficacy and Safety of Metformin and GLP-1 Analogues in Children and Adolescents with Diabetes Mellitus Type 2.

Diabetes mellitus type 2 (DMT2) is one of the most frequent glucose metabolism disorders, in which serum glucose concentrations are increased. In most cases, changes in lifestyle and diet are considered as the first step in addressing its therapy. If changes in lifestyle and diet fail, drugs, such as metformin, must be added. Lately, apart from metformin or insulin, the FDA has approved the use of glucagon-like peptide-1 (GLP-1) analogues for children and adolescents. Little is known about their efficacy and safety at this young age. The main aim of this systematic review/meta-analysis was to assess the safety and efficacy of metformin and GLP-1 analogues, exenatide and liraglutide, compared with placebos or other antidiabetic drugs used for DMT2 in children and adolescents. Metformin did not seem to demonstrate pharmacologic superiority, while GLP-1 analogues were found superior to placebos. GLP-1 analogues may be considered a useful alternative for the treatment of DMT2 in children and adolescents.

Pharmacokinetic and pharmacodynamic modeling of levetiracetam: investigation of factors affecting the clinical outcome.

This study aimed to evaluate the pharmacokinetics and pharmacodynamics of oral levetiracetam therapy in drug refractory adult epileptic outpatients, as well as factors affecting them. Concentration-time data were collected at steady state, while seizure recurrence was monitored for 13 months. Non-linear mixed effects modeling was applied, and covariates assessed included weight, height, age, daily dose and creatinine clearance.Plasma concentrations of levetiracetam were best described by a one-compartment pharmacokinetic model (V/F = 34.7 L) with first-order absorption (ka = 0.616 h-1) and clearance (CL/F = 3.26 L/h). Patient's CrCL was found to significantly affect levetiracetam clearance (beta = 0.795). Time to seizure occurrence followed an exponential distribution and the mean time to seizure occurrence was estimated Te = 22.08 days. Seizure rate per month followed a Poisson distribution, while mean seizure rate per month was estimated λ = 1.33. Daily dose significantly affected the mean estimated time to seizure (beta = -2.2) and the mean monthly seizure rate (beta = 2.27) in a reverse way. Using discrete time Markov chains, it was shown that the transition probability from focal seizures to focal to bilateral tonic-clonic is significantly altered in relation to patient's CrCL.Simulations showed that dose should be adjusted in relation to CrCL, while low doses of levetiracetam are more effective for seizure control. Modeling and simulation in every-day clinical practice may provide significant information for the optimization of seizure control using well-known agents.

Do we need to adopt antifungal stewardship programmes?

Background: Although antimicrobial stewardship programmes are one of the highest priorities in healthcare systems and many articles have been published, few refer to the implementation of antifungal stewardship and highlight specific points on which efforts should be focused. Objective: To assess the percentage of patients with confirmed candidaemia in whom de-escalation was conducted, and the economic impact of step-down or step-up antifungal therapy. Additionally, we attempted to estimate the potential increase in drug minimum inhibitory concentrations or to detect resistant strains of Candida species. Methods: We selected, retrospectively, patients who had received systemic antifungal therapy between 2011 and 2016 for documented candidaemia. Statistical analysis and diagrams were used to assess the results. Results: Of 157 patients with confirmed candidaemia, 58 received azoles, 74 echinocandinsand 18 liposomal amphotericin B for empirical therapy. 51 patients were eligible to step-down to fluconazole but only 23 patients did so. Furthermore, in nine patients unjustified step-up from fluconazole to echinocandins or liposomal amphotericin B was carried out. The additional cost incurred bythe healthcare system due to high prices of echinocandins and liposomal amphotericin B in comparison with fluconazole was€211 837. Interestingly, it was found that one strain of C. albicans and two strains of C. glabrata were resistant to echinocandins. Conclusion: The presence of a multidisciplinary team, including an infection control specialist and a clinical pharmacist, would limit the prescription of advanced antifungal agents as empirical therapy. Moreover, this team would control the de-escalation process-where applicable-leading to a reduction in costs and, probably, a decrease in the emergence of resistant Candida species. These facts contribute to the broader discussion on the adoption of antifungal stewardship programmes.

Systematic review and network meta-analysis of approved medicines for the treatment of idiopathic pulmonary fibrosis.

Background: Clinical practice guidelines for the treatment of idiopathic pulmonary fibrosis (IPF) currently recommend pirfenidone and nintedanib. However, there is a lack of evidence from head-to-head comparisons. Objectives: To perform a systematic review and network meta-analysis (NMA) to access the efficacy and tolerability of two new treatments for IPF, pirfenidone and nintedanib. Methods: Randomized controlled trials (RCTs) selection (CENTRAL, MEDLINE, Embase), data extraction, risk of bias analysis, and GRADE assessment were carried out by two authors separately. Direct estimates were calculated using standard pairwise meta-analysis. A Bayesian mixed treatment comparison approach for NMA estimates, with 95% confidence intervals (CI), was used to compare the treatments, calculating odds ratios (OR) and number needed to treat (NNTB) or harm (NNTH). Results: The NMA on 10 randomized controlled trials showed that each drug had a positive effect on percentage of forced vital capacity (FVC) decline ≥ 10% (pirfenidone OR = 0.54 [95% CI = 0.37-0.80], NNTB = 9 [95% CI = 7-22]; nintedanib OR = 0.59 [95% CI = 0.41-0.84], NNTB = 9 [95% CI = 6-23]), but no significant differences were noted when comparing pirfenidone and nintedanib with respect to acute exacerbations, mortality, and serious adverse events (FVC decline OR = 0.91 [95% CI = 0.45-2.03]) or dropouts (OR = 0.75 [95% CI = 0.33-1.27]). Nintedanib showed an effect on dropouts, OR = 1.61 (1.13-2.28) and NNTH = 14 (8-61). Conclusions: Based on RCTs of 12 month duration in patients with IPF, a positive effect on FVC decline was noted for both treatments and on dropouts for nintedanib, but no significant differences were noted between treatments.

Serum kisspeptin concentrations are negatively correlated with body mass index in adolescents with anorexia nervosa and amenorrhea.

OBJECTIVE: To measure, for the first time, serum kisspeptin concentrations in adolescent females with anorexia nervosa (AN) and associated amenorrhea, and investigate potential correlations of kisspeptin with anthropometric, bone and hormonal data. DESIGN: Setting: University Adolescent Medicine Center. PARTICIPANTS: Females aged 12-20 years with typical or atypical AN (based on DSM-5 diagnostic criteria) and controls. INTERVENTIONS: Measurement of body mass index (BMI), whole body/lumbar spine bone mineral density and serum concentrations of kisspeptin, follicle stimulating hormone, luteinizing hormone (LH), prolactin (PRL), thyroid stimulating hormone (TSH), free thyroxine, triiodothyronine, estradiol (E2), 17-hydroxyprogesterone. MAIN OUTCOME MEASURES: Kisspeptin serum concentrations and correlations between kisspeptin and AN-related anthropometric, bone and hormonal changes. RESULTS: Participants included 37 females, 22 with AN (typical AN group=17, atypical AN group=5) and 15 in the control group. All typical AN patients had secondary amenorrhea. Wide inter-subject variation (101.9-709.1 ng/L) in kisspeptin levels was observed with no significant differences among study groups; there was a trend toward higher concentrations in the atypical AN group. Adolescents with typical AN had significantly lower BMI (P<0.001), lumbar spine z-score (P=0.016), serum E2 (P<0.001), LH (P=0.016), PRL (P=0.034) and TSH (P=0.045) than controls. They also had lower BMI (P=0.009) and TSH (P=0.027) than girls with atypical AN. An inverse correlation between BMI and serum kisspeptin was noted in the typical AN group (r=-0.60, P=0.012). CONCLUSIONS: Serum kisspeptin concentrations overlapped between patients and controls; in typical anorexic adolescents kisspeptin concentrations were negatively correlated with BMI. Future studies are needed to explore kisspeptin physiology in AN.

Ropivacaine, Interleukin-6 and Tumor Necrosis Factor Alpha Plasma Levels during Intermittent Epidural and Continuous Wound Infusion of Ropivacaine for Analgesia after Hysterectomy or Myomectomy: An Observational Study.

BACKGROUND/AIMS: The concentration-time profile of the long-acting local anesthetic ropivacaine after epidural (EP) administration at fixed time intervals or continuous subcutaneous (SC) infusion has not been fully evaluated. The objective of this work was to determine total plasma concentrations of ropivacaine and changes in cytokine interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels during EP and SC. METHODS: In this prospective randomized controlled trial, 18 patients undergoing abdominal hysterectomy or myomectomy were randomly selected to receive ropivacaine either every 6 h via an EP catheter or by continuous wound infusion along the skin incision, after a bolus dose, for 48 h. Total plasma ropivacaine concentrations were measured before the bolus and 2, 4, 8, 24, 48, and 50 h after the bolus using high-performance liquid chromatography-UV and IL-6 and TNF-α levels were measured at 0, 8 and 24 h with ELISA and analyzed statistically. RESULTS: During EP, mean ± SD ropivacaine concentrations were relatively stable up to 50 h postoperatively, that is, 239 ± 89 ng/ml, while during SC, initial concentrations between 2 and 8 h were comparatively lower (101.5 ± 42.9 ng/ml) than 24-50 h concentrations (437.1 ± 206 ng/ml). An increase in IL-6 levels was noted between 0 and 24 h during EP and SC, but TNF-α levels increased slightly, between 0 and 24 h, only during EP. CONCLUSION: Ropivacaine plasma concentrations with both EP and SC were found to be safe throughout the administration time interval. IL-6 levels increased during the same time interval, while TNF levels varied only slightly.

Combined intravenous and intraventricular administration of colistin methanesulfonate in critically ill patients with central nervous system infection.

Colistin pharmacokinetics were prospectively studied after intravenous administration of colistin methanesulphonate in critically ill patients without central nervous system infection (controls, n = 5) and in patients with external ventricular drain-associated ventriculitis after intravenous administration (EVDViv, n = 3) or combined intravenous/intraventricular administration (EVDVcomb, n = 4). Cerebrospinal fluid (CSF)/serum colistin concentration ratios were higher in EVDViv than in control patients (11% versus 7%, P ≤ 0.05) and in EVDVcomb compared to all other patients (P < 0.0001). CSF colistin concentrations above the MIC of 0.5 µg/ml were achieved only in EVDVcomb patients.

Colistin pharmacokinetics in intensive care unit patients on continuous venovenous haemodiafiltration: an observational study.

OBJECTIVES: Available data on colistin pharmacokinetics in patients undergoing continuous renal replacement therapy (CRRT) are limited. Our aim was to study colistin pharmacokinetics in critically ill patients treated with colistin methane sulphonate for Gram-negative sepsis and undergoing continuous venovenous haemodiafiltration for acute renal failure. PATIENTS AND METHODS: Three patients were studied. The colistin methane sulphonate dose administered was at the discretion of the attending physician and was in all cases lower than that recommended for individuals with intact renal function. Colistin methane sulphonate was administered intravenously over 30 min, and blood samples were collected from each patient pre- and post-filter for the HPLC determination of colistin levels in serum before infusion, at 10, 60, 120, 240, 360, 480 and 600 min from the end of infusion, and immediately before the next dose. Concurrently, spot samples of effluent from the haemofilter were also collected and analysed. Both colistin total extracorporeal clearance and clearance in the effluent were calculated. RESULTS: Extracorporeal clearance resulted in substantial removal of colistin (43%-59% of total colistin clearance). Total colistin clearance was found to be reduced (varying between 3.3 and 4.5 L/h), compared with patients with normal renal function. Colistin methane sulphonate dosage resulted in clearly suboptimal colistin steady-state concentrations. CONCLUSIONS: In spite of substantial extracorporeal clearance, total colistin clearance was reduced, compared with patients with normal renal function. Colistin adsorption by the haemofilter contributed to its extracorporeal clearance to a large extent. Studies on other patients receiving colistin methane sulphonate and undergoing CRRT are required before more appropriate dosage regimens can be recommended.

Pharmacokinetics of inhaled colistimethate sodium (CMS) in mechanically ventilated critically ill patients.

PURPOSE: The purpose of this study was to describe inhaled colistin pharmacokinetics in patients with ventilator-associated tracheobronchitis (VAT) due to polymyxin-only susceptible Gram-negative bacteria (GNB). METHODS: Inhaled colistimethate sodium (CMS) was administered at a dose of 80 mg every 8 h for 7 days. Mini bronchoalveolar lavage (BAL) was performed before and at 1, 4 and 8 h, while blood samples were collected before and at 0.16, 0.5, 1, 2, 4 and 8 h after the first dose. Colistin concentrations in BAL and serum were determined by high-performance liquid chromatography. RESULTS: Our study population included 20 patients. At the end of treatment, cure was achieved in 16 patients and favorable microbiological response in 12 patients. Median (25-75 % interquartile range) colistin concentrations in epithelial lining fluid (ELF) were 6.7 (4.8-10.1), 3.9 (2.5-6.0) and 2.0 (1.0-3.8) µg/ml at 1, 4 and 8 h, respectively, and fivefold higher than those achieved in serum. Median ELF concentrations at 1 and 4 h were above the minimum inhibitory concentrations of all isolated pathogens; however, the 4-h median was below the European Committee on Antimicrobial Susceptibility Guidelines (EUCAST) breakpoints for Pseudomonas aeruginosa and the 8-h median was low relative to EUCAST breakpoints for all GNB. Colistin pharmacokinetic/pharmacodynamic parameters in ELF were associated with favorable microbiological response at the end of treatment. CONCLUSION: Inhaled colistin may achieve high drug concentrations in the lung. However, a dose of 80 mg of inhaled CMS every 8 h may not be adequate for the treatment of lower respiratory tract infections due to multi-drug resistant GNB.

Voriconazole pharmacokinetics and photosensitivity in children with cystic fibrosis.

BACKGROUND: A high incidence of adverse skin reactions following long-term oral administration of voriconazole in children with cystic fibrosis and allergic bronchopulmonary aspergillosis (ABPA). The aim was to study the pharmacokinetics of voriconazole in these patients and to determine a possible association between drug levels and adverse effects. METHODS: Multiple venous blood samples were collected for HPLC determination of voriconazole concentrations and routine blood tests. Adverse events were recorded. RESULTS: No significant correlation was found between incidence of photosensitivity and voriconazole serum levels in 6 of 8 children with ABPA. 80% of patients had trough voriconazole concentrations<1000 ng/mL and were highly variable. CONCLUSIONS: Long-term voriconazole therapy and greater sun exposure in Greece appear to play a major role in the occurrence of photosensitivity. Steady-state plasma drug concentrations were found to be highly variable and below the recommended therapeutic range in most patients, without any apparent negative influence on outcome.

Monitoring plasma voriconazole levels following intravenous administration in critically ill patients: an observational study.

Data relating to the pharmacokinetics of voriconazole in critically ill patients are lacking. A prospective observational study was conducted on 18 non-consecutive critically ill patients aged 24-97 years, comprising 12 patients with normal renal function (NRF) [creatinine clearance (CL(Cr)) > or = 60 mL/min] and 6 patients with moderate renal impairment (MRI) (CL(Cr) 40-55 mL/min), administered voriconazole intravenously (6 mg/kg loading dose and 3-4 mg/kg twice daily thereafter) in order to determine the suitability of these doses in this patient population. Steady-state blood levels were monitored and liver and renal function were recorded throughout treatment. Large variability in patient plasma levels was observed, ranging from 37% at < or = 1 mg/L (minimum inhibitory concentration at which, for most fungal pathogens, 90% of isolates are susceptible) to 19% at >5.5mg/L. Moreover, maintaining trough concentrations above clinical breakpoints was not consistently achieved because 16/30 (53%) were < or = 1 mg/L. In a few MRI patients, average concentrations were found to be significantly different compared with those of NRF patients administered the same dose, however this difference was not noted in pharmacokinetic parameters following dose normalisation. None of the patients experienced deterioration in renal or liver function. Recommended voriconazole doses are inadequate to achieve drug concentrations >1 microg/mL over the entire dosing interval in some critically ill patients.

Caffeine versus theophylline for apnea of prematurity: a randomised controlled trial.

AIM: To compare standard doses of theophylline and caffeine for apnea of prematurity in terms of apnea frequency and assess the need for therapeutic drug monitoring. METHODS: Seventy neonates less than 33 weeks gestation, breathing spontaneously, were randomly assigned (open-label) to receive either theophylline or caffeine for treatment or prevention of apnea. The primary outcome measure was the difference in apnea frequency between theophylline and caffeine patient groups. Methylxanthine serum levels were measured on the 1st, 3rd and 7th days of therapy and every 7 days thereafter. RESULTS: Thirty-seven neonates received theophylline (T) and 33 caffeine (C) for treatment (8 T/10 C) or prevention of apnea (29 T/23 C). Treatment with either methylxanthine significantly decreased apnea events (T, P= 0.012; C, P= 0.005) while only C prophylaxis appeared to control apnea in infants at risk. Analysis of combined (treatment plus prophylaxis) data showed a significant decrease in apnea frequency only in those infants receiving caffeine (P= 0.001). However, there was no sustained benefit of C over T beyond the first week of therapy. T and C concentrations (2.2-13.9 mg/L; 5.5-23.7 mg/L, respectively) in the majority of cases fell within the recommended therapeutic ranges and were not significantly associated with apnea events. CONCLUSIONS: This study shows an advantage of C over T for premature infants <33 weeks gestation during the first week of therapy. Standard regimens of both methylxanthines do not seem to require routine concentration monitoring in the first 3 weeks of treatment unless indicated by clinical effect.

Excretion of ropivacaine in breast milk during patient-controlled epidural analgesia after cesarean delivery.

BACKGROUND: Few studies have been published concerning the excretion of bupivacaine and lidocaine into the breast milk and none concerning ropivacaine. AIM: The aim of this study was to determine the levels of ropivacaine in plasma and breast milk after combined spinal-epidural anesthesia for cesarean delivery and postoperative patient-controlled epidural analgesia (PCEA), as well as possible adverse effects from these levels on the neonate. METHODS: Twenty-five parturients admitted for cesarean delivery under combined spinal-epidural anesthesia participated in the study. The PCEA regimen was prepared as 0.15% ropivacaine and fentanyl 2 microg/mL (basal rate, 6 mL/h; demand dose, 4 mL/20 min). Blood samples were collected before anesthesia and from the umbilical cord immediately after birth, followed by blood and breast milk samples 18 and 24 hrs after initiation of PCEA. The newborns were clinically appraised with the Apgar score at delivery and Neurological and Adaptive Capacity Score 24 hrs later. Local anesthetic side effects were recorded. Ropivacaine levels were determined by high-performance liquid chromatography with a UV detector. RESULTS: Ropivacaine excretion into the breast milk produced concentrations that significantly correlated with those in the plasma 18 and 24 hrs after administration, achieving milk-plasma ratios (mean +/- SD) of 0.25 +/- 0.08 and 0.23 +/- 0.07, respectively. Most newborns had maximal Apgar and Neurological and Adaptive Capacity Scores. No adverse effects from ropivacaine were noted in mothers or neonates. CONCLUSIONS: The milk-plasma concentration ratio of ropivacaine was found to be lower than that reported for other local anesthetics It seems that PCEA with ropivacaine/fentanyl after cesarean delivery is not associated with excessive milk-plasma concentrations of ropivacaine.

Netilmicin in the neonate: pharmacokinetic analysis and influence of parenteral nutrition.

OBJECTIVE: The aim of this study was to investigate the impact of parenteral nutrition on netilmicin pharmacokinetics in critically ill neonates during the first week of life. METHOD: A total of 200 neonates (gestational ages 26.4-41 weeks) treated with netilmicin (4-5 mg/kg in extended dosing intervals) for postnatal sepsis in the first week of life received either fluid therapy or parenteral nutrition. Netilmicin peak and trough serum concentrations were monitored and netilmicin pharmacokinetic parameters were compared with and without parenteral nutrition. RESULTS: There were no statistically significant differences between the pharmacokinetic parameters of netilmicin (volume of distribution, elimination half-life, clearance) in critically ill neonates >32 weeks during the first week of life that received either fluid therapy or parenteral nutrition. For neonates <32 weeks this comparison was not feasible as the majority were parenterally fed. CONCLUSION: Provision of parenteral nutrition (versus fluid therapy) in critically ill neonates >32 weeks did not significantly affect netilmicin pharmacokinetics and therefore does not require modification of recommended netilmicin dosage regimens.

Data analysis of the benefits of an electronic registry of information in a neonatal intensive care unit in Greece.

OBJECTIVES: This study assesses the results of implementation of a software program that allows for input of admission/discharge summary data (including cost) in a neonatal intensive care unit (NICU) in Greece, based on the establishment of a baseline statistical database for infants treated in a NICU and the statistical analysis of epidemiological and resource utilization data thus collected. METHODS: A software tool was designed, developed, and implemented between April 2004 and March 2005 in the NICU of the LITO private maternity hospital in Athens, Greece, to allow for the first time for step-by-step collection and management of summary treatment data. Data collected over this period were subsequently analyzed using defined indicators as a basis to extract results related to treatment options, treatment duration, and relative resource utilization. RESULTS AND DISCUSSION: Data for 499 babies were entered in the tool and processed. Information on medical costs (e.g., mean total cost +/- SD of treatment was euro310.44 +/- 249.17 and euro6704.27 +/- 4079.53 for babies weighing more than 2500 g and 1000-1500 g respectively), incidence of complications or disease (e.g., 4.3 percent and 14.3 percent of study babies weighing 1,000 to 1,500 g suffered from cerebral bleeding [grade I] and bronchopulmonary dysplasia, respectively, while overall 6.0 percent had microbial infections), and medical statistics (e.g., perinatal mortality was 6.8 percent) was obtained in a quick and robust manner. CONCLUSIONS: The software tool allowed for collection and analysis of data traditionally maintained in paper medical records in the NICU with greater ease and accuracy. Data codification and analysis led to significant findings at the epidemiological, medical resource utilization, and respective hospital cost levels that allowed comparisons with literature findings for the first time in Greece. The tool thus contributed to a clearer understanding of treatment practices in the NICU and set the baseline for the assessment of the impact of future interventions at the policy or hospital level.

Acute administration of vitamin C abrogates protection from ischemic preconditioning in rabbits.

Vitamin C is considered to be an antioxidant agent that is broadly used. Free radicals are involved in the protective mechanism of preconditioning (PC), but some antioxidant compounds abolish this benefit. The aim of the present study was to evaluate the effect of vitamin C on the protective effect of PC with respect to infarct size and oxidative stress in anesthetized rabbits. Male rabbits were randomly divided into six groups and subjected to 30 min of myocardial ischemia and 3h of reperfusion with the following interventions per group: (1) Control (no intervention), (2) Vit C 150 group (i.v. vitamin C at a total dose of 150 mg/kg for 75 min, starting 40 min before the onset of long ischemia and lasting up to the 5th min of reperfusion), (3) Vit C 300 group (i.v. vitamin C at a total dose of 300 mg/kg as previously described), (4) PC group (two cycles of 5 min ischemia and 10 min reperfusion), (5) combined PC-Vit C 150 group and (6) combined PC-Vit C 300 group. Blood samples were taken at different time points for malondialdehyde (MDA) assessment as a lipid peroxidation marker and for superoxide dismutase (SOD) activity. At the end of the experiment the infarct size was determined. Vitamin C, at both doses, did not reduce the infarct size (35.5+/-4.1%, 38.3+/-7.0% vs. 44.9+/-3.3% in the control group) and diminished the protection afforded by PC (32.0+/-2.7%, 43.8+/-3.3% vs. 15.7+/-2.9% in the PC group, P<0.05). At reperfusion there was an elevation of circulating MDA levels in the control and PC groups while in both vitamin C groups the levels were decreased. SOD activity was enhanced in the PC group compared to the controls; vitamin C did not change SOD activity during ischemia-reperfusion. Vitamin C abrogates the beneficial effect of ischemic PC on infarct size and elicits antioxidant properties during ischemia-reperfusion.

Colistin serum concentrations after intravenous administration in critically ill patients with serious multidrug-resistant, gram-negative bacilli infections: a prospective, open-label, uncontrolled study.

BACKGROUND: The emergence of multidrug-resistant nosocomial pathogens, such as Pseudomonas aeruginosa and Acinetobacter baumannii, has led to the revival of the systemic use of antimicrobial agent colistin in critically ill patients, but only limited data are available to define its pharmacokinetic profile in these patients. OBJECTIVE: The aim of this study was to assess steady-state serum concentrations of colistin after i.v. administration of colistin methanesulfonate (CMS) in critically ill patients with stable kidney function. METHODS: This prospective, open-label, uncontrolled study was conducted at 2 intensive care units in the Athens Trauma Hospital, KAT, Athens, Greece. Adult patients were nonconsecutively enrolled if they were critically ill and had stable kidney function (<0.5 mg/dL change in serum creatinine prior to and until the day of sample collection) and had been receiving CMS as part of a treatment regimen for sepsis irrespective of site of infection with multidrug-resistant, gram-negative bacilli. After i.v. administration of 225-mg CMS (with the exception of 1 patient who received 150 mg) every 8 or 12 hours for at least 2 days, blood samples were collected just before and at 10 minutes and 1, 2, 4, 6, and 8 hours after i.v. infusion (duration, 30 minutes) of the colistin dose on the sampling day. RESULTS: Fourteen nonconsecutive patients were enrolled in the study (13 male, 1 female; mean [SD] age, 62.0 [19.2] years; mean [SD] estimated weight, 72.5 [8.5] kg; mean [SD] Acute Physiology And Chronic Health Evaluation II score on admission, 17.1 [6.0]). At steady state, mean (SD) colistin maximum and minimum concentrations were 2.93 (1.24) and 1.03 (0.44) mg/L, respectively, while mean (SD) apparent total body clearance, apparent volume of distribution, and t(1/2) were 13.6 (5.8) L/h, 139.9 (60.3) L, and 7.4 (1.7) hours, respectively. Colistin-related nephrotoxicity was not observed in the study patients. CONCLUSION: CMS dosage regimens administered to these critically ill adult patients were associated with suboptimal Cmax/MIC ratios for many strains of gram-negative bacilli currently reported as sensitive (MIC, < or = 2 microg/mL).