Near-infrared spectroscopy as a potential non-invasive tool in the assessment of disease activity in vitiligo patients.

Vitiligo is a common chronic depigmenting skin disease. We explored the utility of near-infrared (NIR) spectroscopy in the identification of spectral changes associated with disease activity in vitiligo patients. In vivo spectral measurements were performed directly on the perilesional skin of 70 vitiligo patients. Relative intensities (second derivative) at 1139, 1344, 1646 and 1839 nm appeared to be significantly lower in the perilesional region of patients with active vitiligo compared with stable disease, while the intensity at 1884 nm seemed to be significantly higher. A classification model based on the spectral ranges around those peaks generated a correct prediction in 82.9% of the cases. In conclusion, we can state that NIR spectroscopy could have potential in the assessment of disease activity. However, large-scale prospective studies are necessary to confirm our preliminary results.

Dose optimization of piperacillin/tazobactam in critically ill children.

Objectives: To characterize the population pharmacokinetics of piperacillin and tazobactam in critically ill infants and children, in order to develop an evidence-based dosing regimen. Patients and methods: This pharmacokinetic study enrolled patients admitted to the paediatric ICU for whom intravenous piperacillin/tazobactam (8:1 ratio) was indicated (75 mg/kg every 6 h based on piperacillin). Piperacillin/tazobactam concentrations were measured by an LC-MS/MS method. Pharmacokinetic data were analysed using non-linear mixed effects modelling. Results: Piperacillin and tazobactam blood samples were collected from 47 patients (median age 2.83 years; range 2 months to 15 years). Piperacillin and tazobactam disposition was best described by a two-compartment model that included allometric scaling and a maturation function to account for the effect of growth and age. Mean clearance estimates for piperacillin and tazobactam were 4.00 and 3.01 L/h for a child of 14 kg. Monte Carlo simulations showed that an intermittent infusion of 75 mg/kg (based on piperacillin) every 4 h over 2 h, 100 mg/kg every 4 h given over 1 h or a loading dose of 75 mg/kg followed by a continuous infusion of 300 mg/kg/24 h were the minimal requirements to achieve the therapeutic targets for piperacillin (60% f T >MIC >16 mg/L). Conclusions: Standard intermittent dosing regimens do not ensure optimal piperacillin/tazobactam exposure in critically ill patients, thereby risking treatment failure. The use of a loading dose followed by a continuous infusion is recommended for treatment of severe infections in children >2 months of age.

Augmented renal clearance implies a need for increased amoxicillin-clavulanic acid dosing in critically ill children.

There is little data available to guide amoxicillin-clavulanic acid dosing in critically ill children. The primary objective of this study was to investigate the pharmacokinetics of both compounds in this pediatric subpopulation. Patients admitted to the pediatric intensive care unit (ICU) in whom intravenous amoxicillin-clavulanic acid was indicated (25 to 35 mg/kg of body weight every 6 h) were enrolled. Population pharmacokinetic analysis was conducted, and the clinical outcome was documented. A total of 325 and 151 blood samples were collected from 50 patients (median age, 2.58 years; age range, 1 month to 15 years) treated with amoxicillin and clavulanic acid, respectively. A three-compartment model for amoxicillin and a two-compartment model for clavulanic acid best described the data, in which allometric weight scaling and maturation functions were added a priori to scale for size and age. In addition, plasma cystatin C and concomitant treatment with vasopressors were identified to have a significant influence on amoxicillin clearance. The typical population values of clearance for amoxicillin and clavulanic acid were 17.97 liters/h/70 kg and 12.20 liters/h/70 kg, respectively. In 32% of the treated patients, amoxicillin-clavulanic acid therapy was stopped prematurely due to clinical failure, and the patient was switched to broader-spectrum antibiotic treatment. Monte Carlo simulations demonstrated that four-hourly dosing of 25 mg/kg was required to achieve the therapeutic target for both amoxicillin and clavulanic acid. For patients with augmented renal function, a 1-h infusion was preferable to bolus dosing. Current published dosing regimens result in subtherapeutic concentrations in the early period of sepsis due to augmented renal clearance, which risks clinical failure in critically ill children, and therefore need to be updated. (This study has been registered at Clinicaltrials.gov as an observational study [NCT02456974].).

Flow cytometry-based analysis by Sysmex-UF1000i® is an alternative method in the assessment of periodontal inflammation.

BACKGROUND: Gingivitis is a common inflammatory condition. We explored the value of flow cytometry of saliva in patients with periodontal inflammation. METHODS: A cohort of 249 healthy adults (age range: 18-81 y; 2.5th to 97.5th percentile: 19-66 y) was investigated for caries, dental plaque and gingivitis. Saliva was analyzed using flow cytometry on a Sysmex UF-1000i®. RESULTS: Sysmex UF-1000i® is capable to reproduce reliable measurements of cellular components in saliva. A statistically significant lower number of salivary bacteria was found in patients with gingivitis in comparison with healthy adults (p<0.0001). A significant difference in salivary leukocyte count was found between patients with different gingival index scores (p<0.0005). The gingivitis score was strongly dependent on the number of salivary leukocytes, the age of the patient and the degree of caries and dental plaque (r(2)=0.60, p<0.001). At a cut-off level of 10(3) leukocytes/µl saliva, an area under the curve of 0.82 was obtained with a sensitivity of 76% and a specificity of 78% in patients (>35 y) with a gingivitis score of 3. CONCLUSION: Flow cytometry is an alternative method to evaluate local inflammatory processes in the mouth with a sensitivity of 76% and a specificity of 78%.

Development of an affordable dye-stained microalbuminuria screening test.

BACKGROUND: A simple spot test was developed, which allows quantification of microalbuminuria. Evaluation was carried out according to the ISO 15189 guidelines. METHODS: Urine was spotted on cellulose acetate strips and stained using different sensitive protein binding dyes (nigrosin, Coomassie Blue R-250, amido black). The colour intensity of the stained spots was quantified using a Kodak Image 450 station. RESULTS: Analytical sensitivity of the Coomassie Blue based method (18 mg/L) was better than that for nigrosin (50 mg/ L) or amido black (100 mg/L) based methods. Within-run coefficient of variation (CV) and between-run CV of the Coomassie blue assay were, respectively, 8.4% and 9.7% (50 mg/L), and 3% and 4.5% (400 mg/L). For nigrosin, these data were, respectively, 8.4 and 9.4 (50 mg/L), and 3.4 and 6.4% (400 mg/L). Coomassie Blue showed a preferential binding selectivity towards albumin. The method was found to be linear between 20 and 600 mg/L. A good correlation (r2 = 0.89) was obtained between Coomassie Blue based and immunonephelometric measurements. Immuno-unreactive albumin (prepared by protease treatment) could be detected by the spot test, which offers an advantage of the method versus immunochemical tests. Ammonium sulphate precipitation could further increase the specificity of the assay by eliminating effects of free light chains. CONCLUSION: The described method is very simple and extremely cheap, which makes it potentially suited for screening programmes, particularly in third world countries.

Assessment of renal function in recently admitted critically ill patients with normal serum creatinine.

BACKGROUND: Detection of renal dysfunction is important in critically ill patients, and in daily practice, serum creatinine is used most often. Other tools allowing the evaluation of renal function are the Cockcroft-Gault and MDRD (Modification of Diet in Renal Disease) equations. These parameters may, however, not be optimal for critically ill patients. The present study evaluated the value of a single serum creatinine measurement, within normal limits, and three commonly used prediction equations for assessment of glomerular function (Cockcroft-Gault, MDRD and the simplified MDRD formula), compared with creatinine clearance (Ccr) measured on a 1 h urine collection in an intensive care unit (ICU) population. METHODS: This was a prospective observational study. A total of 28 adult patients with a serum creatinine <1.5 mg/dl, within the first week of ICU admission, were included in the study. Renal function was assessed with serum creatinine, timed 1 h urinary Ccr, and the Cockcroft-Gault, MDRD and simplified MDRD equations. RESULTS: Serum creatinine was in the normal range in all patients. Despite this, measured urinary Ccr was <80 ml/min/1.73 m2 in 13 patients (46.4%), and <60 ml/min/1.73 m2 in seven patients (25%). Urinary creatinine levels were low, especially in patients with low Ccr, suggesting a depressed production of creatinine caused by pronounced muscle loss. Regression analysis and Bland-Altman plots revealed that neither the Cockcroft-Gault formula nor the MDRD equations were specific enough for assessment of renal function. CONCLUSIONS: In recently admitted critically ill patients with normal serum creatinine, serum creatinine had a low sensitivity for detection of renal dysfunction. Furthermore, the Cockcroft-Gault and MDRD equations were not adequate in assessing renal function.