Amikacin population pharmacokinetics among paediatric burn patients

Introduction

The objectives of this study were to (1) determine the pharmacokinetics of amikacin among children with severe burn and (2) identify influential covariates.

Methods

Population-based pharmacokinetic modelling was performed in NONMEM 7.2 for hospitalized children who received amikacin at 10–20 mg/kg divided two, three, or four times per day as part of early empiric treatment of presumed burn-related sepsis.

Results

The analysis included data from 70 patients (6 months to 17 years) with 282 amikacin serum concentrations. Amikacin's mean C_max was 33.2 ± 9.4 μg/mL and the mean C_min was 3.8 ± 4.6 μg/mL. The final covariate model estimated clearance as 5.98 L/h/70 kg (4.97–6.99, 95% CI), the volume of distribution in the central compartment as 16.7 L/70 kg (14.0–19.4, 95% CI), the volume of distribution in the peripheral compartment as 40.1 L/70 kg (15.0–80.4, 95% CI), and the inter-compartmental clearance as 3.38 L/h/70 kg (2.44–4.32, 95% CI). In multivariate analyses, current weight (P < 0.001) was a significant covariate, while age, sex, height, serum creatinine, C-reactive protein, platelet count, the extent and type of burn, and concomitant vancomycin administration did not influence amikacin pharmacokinetics.

Discussion

Children with burn featured elevated amikacin clearance when compared to healthy adult volunteers. However, peak amikacin concentrations are comparable to those attained in other critically-ill children, suggesting that elevated amikacin clearance may not result in sub-therapeutic antibacterial effects. In this study, we found that amikacin displays two-compartment pharmacokinetics, with weight exerting a strong effect upon amikacin clearance. Further pharmacodynamic studies are needed to establish the optimal dosing regimen for amikacin in paediatric burn patients.     

Design and Synthesis of a Mitochondria-Targeted Mimic of Glutathione Peroxidase,MitoEbselen-2, as a Radiation Mitigator

相似文献   

Dose dependency between cigarette consumption and reduced maternal serum PAPP-A levels at 11-13+6 weeks of gestation

OBJECTIVE: To examine whether in smokers there is a significant dose dependency between the number of cigarettes per day and levels of free ss-hCG and pregnancy-associated plasma protein A (PAPP-A) at 11-13(+6) weeks of gestation. METHODS: This was a retrospective analysis of the maternal serum free ss-hCG and PAPP-A levels in relation to the maternal smoking status in 109 263 chromosomally normal singleton pregnancies that had undergone first-trimester screening for Down syndrome by a combination of fetal nuchal translucency thickness and maternal serum biochemistry. RESULTS: There were 95 287 nonsmokers and 13 976 cigarette smokers. The overall median PAPP-A MoM among cigarette smokers was 0.827, which was 19.6% lower than the value of 1.029 in nonsmokers (p < 0.0001 for log(10) MoM). The respective values for beta-hCG MoM were 1.003 for smokers and 1.035 for nonsmokers (p < 0.0001 for log(10) MoM) which corresponds to a reduction of 3.1%. There was a significant inverse relationship between the number of cigarettes per day and the level of PAPP-A MoM (r = 0.989, p < 0.0001) but not the level of free beta-hCG MoM (r = 0.733; p = 0.098). Using a statistical modeling approach we found that the screen-positive rate when correcting the PAPP-A MoM by an all or nil smoking factor was reduced by only 0.1% (3.75 vs 3.85%) when compared to correcting with a factor related to the smoking dose per day. CONCLUSION: In first-trimester screening for Down syndrome by maternal serum PAPP-A and free beta-hCG the impact of correcting for the dose dependant rather than the all or nil effect of smoking is marginal. However, a dose dependent correction improves the accuracy of the individual patient-specific risk.     

Correlations between First 72 h Hypophosphatemia,Energy Deficit,Length of Ventilation,and Mortality—A Retrospective Cohort Study

Introduction. Hypophosphatemia may prolong ventilation and induce weaning failure. Some studies have associated hypophosphatemia with increased mortality. Starting or restarting nutrition in a critically ill patient may be associated with refeeding syndrome and hypophosphatemia. The correlation between nutrition, mechanical ventilation, and hypophosphatemia has not yet been fully elucidated. Methods. A retrospective cohort study of 825 admissions during two consecutive years was conducted. Using the electronic medical chart, demographic and clinical data were obtained. Hypophosphatemia was defined as a phosphate level below 2.5 mg/dL (0.81 mmol/L) in the first 72 h of ICU admission. Comparisons between baseline characteristics and outcomes and multivariate analysis were performed. Results. A total of 324 (39.27%) patients had hypophosphatemia during the first 72 h of ICU admission. Patients with hypophosphatemia tended to be younger, with lower APACHE-II, SOFA24, and ΔSOFA scores. They had a longer length of stay and length of ventilation, more prevalent prolonged ventilation, and decreased mortality. Their energy deficit was lower. There was no effect of hypophosphatemia severity on these results. In multivariate analysis, hypophosphatemia was not found to be statistically significant either with respect to mortality or survivor’s length of ventilation, but lower average daily energy deficit and SOFA24 were found to be statistically significant with respect to survivor’s length of ventilation. Conclusion. Hypophosphatemia had no effect on mortality or length of ventilation. Lower average daily energy deficit is associated with a longer survivor’s length of ventilation.     

Practical Parameters in the Use of Flooding for Treating Chronic PTSD

While flooding or direct therapeutic exposure (DTE) has been empirically validated as an effective primary treatment for PTSD through several randomized controlled trials, there is also evidence that relatively few trauma therapists actually use the technique. There are now several published reports which document a number of the difficulties in implementing the treatment with chronic PTSD patients. These problems, ranging from patient refusal to adverse reactions, represent several domains, including trauma history characteristics, patients' personal characteristics, therapist factors, and treatment environment factors. The purpose of the present report is to provide an empirical rationale to support the use of individual flooding as a primary form of psychotherapy for chronic combat-related PTSD. Implementation rates for flooding are compared among expert behavioural trauma therapists versus field use rates for trauma programmes generally. Complications or side-effects of flooding are considered. We also identify several predictable sources of difficulty in implementing individual flooding and the proportions of patients likely to be affected by each type. Finally, practical suggestions are offered for improving utilization of flooding, and directions for future empirical investigations are explored.     

Trait Emotional Intelligence and Internet Gaming Disorder Among Gamers: The Mediating Role of Online Gaming Motives and Moderating Role of Age Groups

Personality differences are important determinants of problematic online behaviors. The purpose of the present study was to investigate the mediating role of loneliness, depression, and online gaming motives and moderating role of age on the relationship between trait emotional intelligence (EI) and Internet gaming disorder (IGD) via the construction of a multiple mediation model. A total of 478 online gamers completed a self-report online survey, including validated psychometric scales assessing the aforementioned constructs. Results indicated that trait EI was directly and indirectly associated with IGD and that the motive of escape was a partial mediator between trait EI and IGD among the total sample and adult gamers, but not among adolescents. Moreover, trait EI was associated with coping, skill development, fantasy, and recreation gaming motives only among total sample and adult gamers, and the escape motive was positively associated with IGD among total sample and adult gamers. However, among these relationships, only the association between trait EI and fantasy was significantly moderated by age group. Furthermore, the direct effect of trait EI was stronger among adolescent gamers when compared to adult gamers. Results showed that trait EI is inversely associated with IGD and affects gaming for different motives among adolescent and adult gamers.

     

Neuroticism,Trait Fear of Missing Out,and Phubbing: The Mediating Role of State Fear of Missing Out and Problematic Instagram Use

International Journal of Mental Health and Addiction - One of the relatively new negative consequences of smartphone use is “phubbing” (snubbing someone while an individual checks their...     

Screening for trisomy 21 in twin pregnancies in the first trimester: an update of the impact of chorionicity on maternal serum markers

OBJECTIVE: To examine the distribution of first-trimester biochemical markers of aneuploidy in twin pregnancies, and to assess whether there are differences in the distributions between monochorionic and dichorionic twins. METHODS: Maternal serum-free beta-hCG and PAPP-A were measured between 11 + 0 and 13 + 6 weeks as part of a routine first-trimester screening program in conjunction with fetal nuchal translucency (NT) performed at two sites. Data from twin pregnancies were extracted from the fetal databases along with information on the chorionicty. The individual marker concentrations were expressed as weight corrected, ethnicity corrected, smoking corrected and IVF corrected MoM using data from singleton pregnancies as the reference. The overall medians were compared to those in singleton pregnancies and between monochorionic and dichorionic twins. RESULTS: Data was available from 1914 sets of twins. Of these, 1214 had information with respect to chorionicity, with 1024 being dichorionic and 190 being monochorionic. The overall median weight corrected, ethnicity corrected, smoking corrected and IVF corrected MoM amongst twin pregnancies were 2.023 for free beta-hCG (sd log(10) MoM = 0.2611 and 2.121 for PAPP-A (sd log(10) MoM = 0.2255) -- both medians were significantly greater than the medians in singleton pregnancies (1.00 MoM). In the case of monochorionic and dichorionic twins the median weight corrected, ethnicity corrected, smoking corrected and IVF corrected, free beta-hCG MoM's were not significantly different (1.983 v 2.041), however for PAPP-A the median weight corrected, ethnicity corrected, smoking corrected and IVF corrected MoM in monochorionic twins was significantly lower than in dichorionic twins (1.756 v 2.250) whilst the sd log(10) MoM's were not significantly different (0.2185 v 0.2167). CONCLUSION: Screening in twin pregnancies requires adjustment of the calculated MoM to account for the presence of two fetuses. In general, for free beta-hCG, this should be by dividing the observed corrected MoM by 2.023. For PAPP-A two different factors are required - 2.192 in dichorionic twins and 1.788 in monochorionic twins.     

Single-Port Laparoscopic Liver Resection: Largest Turkish Experience

Single-port laparoscopic surgery has the advantage of a hidden scar and reduced abdominal wall trauma. Although single-port laparoscopic surgery is widely performed for other organs, its application is very limited for liver resection. Here, we report our experience with nine patients who underwent single-port laparoscopic liver resection. Nine patients underwent single-port laparoscopic liver resection for the indications of hydatid cyst, hepatocellular carcinoma, and colorectal cancer liver metastasis. Nine patients were successfully treated with single-port laparoscopic surgery. The operative time was between 60 and 240 min. The only operative complication was bleeding up to 650 mL in a patient with cirrhosis. No postoperative complications occurred. All patients were discharged earlier than usual. Single-port laparoscopic liver surgery is a challenging surgery. Surgeon with the experience of laparoscopic liver surgery should perform the single-port laparoscopic liver surgery. It is technically feasible with a good outcome in well-selected patients. Initial cases must be benign lesions to avoid jeopardizing oncological safety.